Intravenous Drug Research Articles

Depressive disorders and intravenous drug use in chemsex context

IntroductionSeveral studies have called atention to the mental health disorders associated with chemsex -the intentional use of drugs before or during sexual intercourse GBMSM (gay, bisexual and men who have sex with men) population-. Sexualized intravenous drug use is also known as slam or slamsex. There are few studies that analyze the mental health differences between intravenous drug users compared to non-intravenous drug users in chemsex context.ObjectivesWe aim to describe the mental health outcomes including current and past depressive disorders diagnosis in a sample of users with sexualized drug use (chemsex) attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” and to compare the differences of current and previous diagnosis of depressive disorders between intravenous drug users compared to non-intravenous drug users.MethodsA cross-sectional descriptive analysis of a sample of users attended by the non-govenrmental organization Apoyo Positivo in the program “Sex, Drugs and You” between 2016-2019 was performed.ResultsWe included 217 participants. Current or past diagnosis of depression was found in 137 participants. Depressive disorders were significantly higher in the intravenous drug use group compared to the non-intravenous drug use group (p<0.05).ConclusionsOur study reports high levels of depression in chemsex users. The participants in our sample who engaged in intravenous drug use presented a higher frequency of depressive disorders than non intravenous drug use participants. Further studies analyzing the relationship between chemsex, slamsex and depresssion are needed. A multidisciplinary team is necessary to address chemsex and provide care and mental health treatment to chemsex users.Disclosure of InterestNone Declared

Drug-induced psychosis and intravenous drug use in chemsex context

Introduction Several studies have called atention to the mental health disorders associated with chemsex -the intentional use of drugs before or during sexual intercourse GBMSM (gay, bisexual and men who have sex with men) population-. Sexualized intravenous drug use is also known as slam or slamsex. There are few studies that analyze the mental health differences between intravenous drug users compared to non-intravenous drug users in chemsex context.ObjectivesWe aim to analyze the relationship between the practice of slamsex and the development of drug-induced psychosis.Methods A cross-sectional descriptive analysis of a sample of users attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” between 2016-2019 was performed.ResultsWe included 217 participants. Drug-induced psychosis was found in 80 participants. Drug-induced psychosis was significantly higher in the intravenous drug use group compared to the non-intravenous drug use group (p<0.05).ConclusionsPrevious studies have reported that MSM who practiced chemsex were more likely to experience from different mental health disorders, being psychosis one of the most frequent psychiatric diagnoses. In our study, drug-induced psychosis was higher in participants who engaged in intravenous drug use. Further studies analyzing the relationship between slamsex and drug-induced psychosis are needed.Disclosure of InterestNone Declared

Anxiety disorders and intravenous drug use in chemsex context

IntroductionSeveral studies have called atention to the mental health disorders associated with chemsex -the intentional use of drugs before or during sexual intercourse GBMSM (gay, bisexual and men who have sex with men) population-. Sexualized intravenous drug use is also known as slam or slamsex. There are few studies that analyze the mental health differences between intravenous drug users compared to non-intravenous drug users in chemsex context.ObjectivesWe aim to describe the mental health outcomes including current and past anxiety disorders diagnosis in a sample of users with sexualized drug use (chemsex) attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” and to compare the differences of current and previous diagnosis of anxiety disorders between intravenous drug users compared to non-intravenous drug users.MethodsA cross-sectional descriptive analysis of a sample of users attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” between 2016-2019 was performed.ResultsWe included 217 participants. Current or past diagnosis of anxiety disorders was found in 142 participants. Anxiety disorders were significantly higher in the intravenous drug use group compared to the non-intravenous drug use group (p<0.05).ConclusionsPrevious studies have reported that MSM who practiced chemsex were more likely to experience from anxiety. In our study, anxiety disorders where higher in participantes who engaged in intravenous drug use. A multidisciplinary team is necessary to address chemsex and provide care and treatment for mental health problems such as anxiety, depression, suicidal behaviour or drug-induced psychosis.Disclosure of InterestNone Declared

Suicidal behaviour and intravenous drug use in chemsex context

IntroductionSeveral studies have called atention to the mental health disorders associated with chemsex --the intentional use of drugs before or during sexual intercourse GBMSM (gay, bisexual and men who have sex with men) population-. Sexualized intravenous drug use is also known as slam or slamsex. There are few studies that analyze the mental health differences between intravenous drug users compared to non-intravenous drug users in chemsex context.ObjectivesTo describe the suicidal behaviour in a sample of users with sexualized drug use (chemsex) attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” and to compare the suicidal behaviour between intravenous drug users compared to non-intravenous drug users.MethodsA cross-sectional descriptive analysis of a sample of users attended by the non-governmental organization Apoyo Positivo in the program “Sex, Drugs and You” between 2016-2019 was performed.ResultsWe included 217 participants. 37 had attempted suicide at least once. The percentage of chemsex users who have attempted suicide were significantly higher in the intravenous drug use group compared to the non-intravenous drug use group (p<0.05).ConclusionsPossible risk factors for suicidal behaviour among chemsex users include slamsex. Other possible risk factors previously described in other studies include adversities experienced due to one’s sexual orientation and an increased risk for HIV and other STI infections. Further studies analyzing the relationship between chemsex, slamsex and suicidal behaviour are needed.Disclosure of InterestNone Declared

Patient-Related Predictors of Treatment Failure After Two-Stage Total Hip Arthroplasty Revision for Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis

BackgroundPeriprosthetic joint infection (PJI) treatment has high failure rates even after 2-stage revision. Risk factors for treatment failure (TF) after staged revision for PJI are not well defined, nor is it well established how they correlate with the risks of developing an index PJI. Identifying modifiable risk factors may allow preoperative optimization, while identifying nonmodifiable risk factors can influence surgical options or advise against further surgery. We performed a systematic review and meta-analysis to better define predictors of TF in 2-stage revision for PJI. MethodsThe PubMed, Embase, and Scopus databases were searched from their inception in December 1976 to April 15, 2023. Studies comparing patient-related variables between patients successfully treated who had 2-staged revision total hip arthroplasty (THA) and patients with persistent infections were included. Studies were screened, and 2 independent reviewers extracted data, while a third resolved discrepancies. Meta-analysis was performed on these data. There were 10,052 unique studies screened, and 21 studies met the inclusion criteria for data extraction. ResultsThere was good-quality evidence that obesity, liver cirrhosis, and previous failed revisions for PJI are nonmodifiable risk factors, while intravenous drug use (IVDU) and smoking are modifiable risk factors for TF after 2-stage revision for hip PJI. Reoperation between revision stages was also significantly associated with an increased risk of TF. Interestingly, other risk factors for an index PJI including male gender, American Society of Anesthesiology score, diabetes mellitus, and inflammatory arthropathy did not predict TF. Evidence on Charlson Comorbidity Index was limited. ConclusionsPatients with a smoking history, obesity, IVDU, previous failed revision for PJI, reoperation between stages, and liver cirrhosis are more likely to experience TF after 2-stage revision THA for PJI. Modifiable risk factors include smoking and IVDU and these patients should be referred to services for cessation as early as possible before 2-stage revision THA.

Injection network drivers of HIV prevention service utilization among people who inject drugs: results of a community-based sociometric network cohort in New Delhi, India.

Injection drug networks may influence their network members' health-seeking behaviours. Using data from a sociometric injecting partner network of people who inject drugs (PWID) in New Delhi, India, we assessed the role of injecting partner (alter) behaviours on individual engagement in HIV prevention services. We enumerated injecting partner linkages among 2512 PWID using coupon referrals and biometric data from November 2017 to March 2020. Participants completed interviewer-administered questionnaires and provided information on injection behaviours, injecting partners, HIV/hepatitis C (HCV) testing and service engagement. Multilevel multiple-membership models (MMMM) evaluated individual PWID HIV testing, medication for opioid use disorder (MOUD) and syringe service engagement as a function of alter attributes, accounting for membership across multiple ego-networks. Logistic regression models assessed parallel associations among socially proximal injecting peers, defined as PWID ≤3 path length from ego. Median age was 26 years; 99% were male. PWID had median 2 injecting partners and 8 socially proximal peers; 14% reported HIV testing, 33% accessed MOUD and 13% used syringe services 6 months prior. In MMMM analyses, PWID with ≥1 versus 0 injecting partners who received HIV testing were significantly more likely to report HIV testing (adjusted odds ratio [aOR]: 2.27, 95% confidence interval [CI]: 1.68-3.16), MOUD (aOR: 1.99, 95% CI: 1.60-2.53) and syringe service use (aOR: 1.66, 95% CI: 1.21-2.39). We observed similar findings for individual MOUD and syringe service use. Having ≥1 versus 0 HIV-positive partners was associated with decreased HIV testing and MOUD but increased syringe service use (aOR: 1.54, 95% CI: 1.09-2.17). PWID with ≥1 versus 0 socially proximal peers who used non-sterile injection equipment reported increased HIV testing (aOR: 1.39, 95% CI: 1.01-1.92), MOUD (aOR: 1.40, 95% CI: 1.10-1.77) and syringe service use (aOR: 1.82, 95% CI: 1.23-2.68). We found differential associative relationships between individual HIV prevention service engagement and the health or risk behaviours of direct and indirect alters. Characterizing network exposure beyond direct injecting partnerships provided important context on possible mechanisms of behavioural influence. Findings could be leveraged to design peer-based interventions that promote network diffusion of health-seeking behaviours.

169 A Case of Kidney Amyloidosis in an Intravenous Drug User

169 A Case of Kidney Amyloidosis in an Intravenous Drug User

Percutaneous Thrombovegectomy as an Alternative to Surgery for Tricuspid Valve Endocarditis

BackgroundUndergoing an urgent valve surgical procedure to treat patients with tricuspid valve endocarditis carries a high risk of operative morbidity and mortality. Use of a percutaneous vacuum-assisted system to treat tricuspid valve endocarditis is an alternative to surgical procedures. MethodsThis study retrospectively analyzed data from 187 transcatheter vacuum-assisted aspiration procedures performed in 177 patients with tricuspid valve vegetations at 3 different centers between 2017 and April 2022. The device was deployed through the internal jugular or femoral vein into the right atrium by using transesophageal echocardiography and fluoroscopy guidance with the return cannula placed in the femoral vein. The following data were analyzed: intravascular material aspirated, collected in an external filter, and cultured; hospital length of stay; procedural complications; blood culture clearance; and tricuspid regurgitation. ResultsThe mean age of participants was 35.5 ± 10.8 years (range, 18-79 years). A total of 107 procedures (57.2%) were performed in female patients, and 163 (87.2%) procedures were performed in intravenous drug users. All patients survived the procedure, and there were no procedural complications. The average length of stay was 26.8 ± 18.5 days (range, 1-96 days). Most preoperative positive blood cultures showed Staphylococcus aureus (80.3%), with postoperative cultures converting to negative in 103 (70.1%) of 147 procedures. Tricuspid regurgitation remained unchanged after 95 (50.8%) procedures and worsened after 40 (21.4%) procedures. ConclusionsPercutaneous vacuum-assisted aspiration system provides a safe alternative to urgent tricuspid valve surgical procedures for removal of vegetations, especially in patients with endocarditis. Initial vegetation debulking can expedite clearance of blood cultures while avoiding major cardiac surgery operations and implantation of prosthetic valves in these high-risk patients.

Broken needles: A hidden and underreported risk among intravenous drug users.

Broken needles: A hidden and underreported risk among intravenous drug users.

Heart failure — An unexplored risk factor for infective endocarditis after pacemaker implantation

BackgroundWith the widespread use of permanent pacemakers (PPM), and increased mortality associated with pacemaker endocarditis, it is essential to evaluate comorbidities that could potentially increase the risk of infective endocarditis (IE). Heart failure (HF), a common comorbidity, has not been well studied as an independent risk factor for development of IE in individuals with PPM. MethodsThe US National Inpatient Sample database was used to sample individuals with PPM. Patients with concomitant implantable cardioverter defibrillator, acute heart failure, history of endocarditis, intravenous drug use, prosthetic heart valves, or central venous catheter infection were excluded. Propensity matching was performed to match patients with and without HF. Pre- and post-match logistic regression was performed to assess HF as an independent risk factor for IE. A subgroup analysis was performed comparing IE rates between patients with HF with reduced (HFrEF) vs preserved (HFpEF) ejection fraction. ResultsOut of 333,571 patients with PPM included in the study, 121,862 (37 %) had HF. HF patients were older and had a higher prevalence of females. All comorbidities except for dental disease and cancer were more prevalent in the HF group. Patients with HF were 1.30 times more likely to develop IE [OR: 1.30 (1.16–1.47); p < 0.001]. The two cohorts were then matched for age, gender, and 20 comorbidities using a 1:1 propensity score matching algorithm. After matching, HF was still independently associated with increased risk of IE [OR: 1.62 (1.36–1.93); p < 0.001]. In our sub-group analysis, HFrEF and HFpEF patients had similar IE rates. ConclusionIn PPM population, HF was associated with an increased risk of IE compared to those without HF. We hypothesize that HF being a low-flow and high-inflammatory state might have contributed to this increased risk. Larger studies are required to corroborate our findings and evaluate the need for antimicrobial prophylaxis for this population.

Evolution of Intravenous Medication Errors and Preventive Systemic Defenses in Hospital Settings-A Narrative Review of Recent Evidence.

Intravenous drug administration has been associated with severe medication errors in hospitals. The present narrative review is based on a systematic literature search, and aimed to describe the recent evolution in research on systemic causes and defenses in intravenous medication errors in hospitals. This narrative review was based on Reason's theory of systems-based risk management. A systematic literature search covering the period from June 2016 to October 2021 was conducted on Medline (Ovid). We used the search strategy and selection criteria developed for our previous systematic reviews. The included articles were analyzed and compared to our previous reviews. The updated search found 435 articles. Of the 63 included articles, 16 focused on systemic causes of intravenous medication errors, and 47 on systemic defenses. A high proportion (n = 24, 38%) of the studies were conducted in the United States or Canada. Most of the studies focused on drug administration (n = 21/63, 33%) and preparation (n = 19/63, 30%). Compared to our previous review of error causes, more studies (n = 5/16, 31%) utilized research designs with a prospective risk management approach. Within articles related to systemic defenses, smart infusion pumps remained most widely studied (n = 10/47, 21%), while those related to preparation technologies (n = 7/47, 15%) had increased. This narrative review demonstrates a growing interest in systems-based risk management for intravenous drug therapy and in introducing new technology, particularly smart infusion pumps and preparation systems, as systemic defenses. When introducing new technologies, prospective assessment and continuous monitoring of emerging safety risks should be conducted.

Exposure to potentially lethal weapons and drugs among U.S. adolescents with recent depressive symptoms or suicidality in the Adolescent Behaviors and Experiences Survey.

The scope of lethal means exposure (i.e. guns, intravenous drugs, prescription drugs) relative to depressive symptoms and suicidality in adolescents is not well described. Using the Adolescent Behaviors and Experiences Survey (ABES), we found lethal means exposure increased in a dose dependent manner with increasing depressive symptoms, adjusting for age, sex, race, and ethnicity. Adolescent males were more than 6 times more likely to have exposure to guns and intravenous drugs compared to adolescent females.

Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry

BackgroundIn recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings.MethodsWe conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use.ResultsWe interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment.ConclusionIn a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Perspectives on Injectable HIV Pre-Exposure Prophylaxis: A Qualitative Study of Health Care Providers in the United States.

The introduction of injectable HIV pre-exposure prophylaxis (PrEP) has the potential to significantly change the biomedical HIV prevention landscape. However, effective implementation will require health care providers to adopt, prescribe, and administer injectable PrEP within clinical settings. This study qualitatively examined challenges and benefit of injectable PrEP implementation from the perspective of health care providers. From April to August 2022, we conducted 19 in-depth interviews with current PrEP-prescribing health care providers in New York State, including 3 physician assistants, 5 physicians, and 11 nurse practitioners. Interviews were audio-recorded, transcribed verbatim, and thematically analyzed to report semantic-level themes regarding injectable PrEP implementation. More than half of participants (61%) were aware of injectable PrEP; only 21% had experience prescribing it. Qualitative findings highlighted five themes. Three themes represented implementation challenges, including speculative concerns about side effects, appointment compliance, and practical and logistical considerations. The remaining two themes described benefits of injectable PrEP relative to oral PrEP, which included greater convenience and enhanced privacy. Findings from this qualitative study make significant applied contributions to the sparse knowledge on health care provider perspectives of injectable PrEP post-US Food and Drug Administration approval and their concerns and considerations regarding implementation in real-world clinical settings.

Primary Hyperaldosteronism: A Rare Potential Risk Factor for Acute Aortic Dissection, an Interesting Case Report

Primary hyperaldosteronism is overproduction of aldosterone from the adrenal cortex with wide electrolyte imbalance and cardiovascular complications like aortic dissection. While the association between primary hyperaldosteronism and aortic dissection has been a subject of interest, the exact relationship and potential causative mechanisms remain unclear. We present here a 51-year-old male with no significant past medical history who came to the emergency department with severe chest pain, sudden-onset radiating to the back, shortness of breath (SOB), and diaphoresis. A chest-to-abdominal Computed Tomography (CT) angiography showed a small tear in the inner lining of the aortic arch, just below the left subclavian artery. The descending aorta had a large mural thrombosis up to the T7 level. The pressure was controlled with intravenous drugs, and then oral antihypertensive drugs and electrolytes were corrected. The patient was recommended to go outside where cardiovascular surgery is available and is now doing well in cardiology outpatient follow-up with well-controlled blood pressure.

Radiotherapy Combined with a Radiosensitizer for Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Carcinoma In Situ Bladder Cancer: An Open-label, Single-arm, Multicenter, Phase 2 European Organisation for Research and Treatment of Cancer Trial

Radical cystectomy with pelvic lymph node dissection and urinary diversion is the standard of care for patients with bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). However, many patients are unwilling or unable to undergo such major surgery associated with high morbidity and a negative impact on quality of life. Chemoradiotherapy is an established treatment option for muscle-invasive bladder cancer. However, it has not been investigated adequately in NMIBC until now. The European Organisation for Research and Treatment of Cancer (EORTC) 2235 study (NCT06310369) is designed as a multicenter, prospective, international, phase 2 trial of moderate hypofractionated radiotherapy combined with a radiosensitizer in BCG-unresponsive NMIBC patients with carcinoma in situ (CIS) who are not eligible for or declined to undergo radical cystectomy. Patients who have received nadofaragene firadenovec or TAR-200 are eligible. The primary endpoint is the 6-mo complete response (CR) rate defined by the absence of CIS proven by a control biopsy of the bladder. The secondary endpoints include overall survival, progression-free survival, durability of CR, grade 3–4 adverse events rate, patients’ quality of life, and organ preservation rate. Patient summaryIntravesical instillation of bacillus Calmette-Guérin is the standard treatment of non–muscle-invasive, also coined as superficial, bladder cancer. In case the cancer recurs, even superficially, there is no other proven treatment than a radical cystectomy—the surgical removal of the bladder. Although the surgical technique has improved dramatically over the past few years, it remains contraindicated in patients with severe comorbidities. In addition, because it affects the quality of life, patients may reject this option. This study will assess the efficacy of external beam radiotherapy, a robust alternative to surgery in muscle-invasive bladder cancer. Radiotherapy will be administered 5 d a week for 4 wk. It will be associated with a “radiosensitizer,” an intravenous or oral drug, during the radiotherapy treatment. The study will measure the proportion of patients remaining recurrence free at 6 mo and thereafter. It will also evaluate the safety of the treatment and its impact on quality of life.

Overview of approved psychiatric medications 2008-2023: A systematic review

Objective: The purpose of this systematic review is to enumerate the psychiatric medications approved by the Food and Drug Administration (FDA) over the past 15 years, from 2008 to 2023, and describe their mechanism of action, approved indications, dosing ranges, and adverse effects. Methods: Studies published from 2008 to 2023 were identified from the PubMed database, using the keywords: ‘psychiatric’ OR ‘psychopharm*” AND ‘medic*’ OR ‘pharm*’. An independent focused analysis was conducted, and a consensus was reached on the studies for approved medications to be included in this systematic review. Key findings were derived from the full-text and tables of the selected studies. Results: From 2008-2023, the FDA approved 118 medications including: 26 for Schizophrenia, 12 for Bipolar Disorders, 16 for Depressive Disorders, two for Anxiety Disorders, one for Feeding and Eating disorders, 13 for Sleep-Wake Disorders, five for Sexual Dysfunctions, 16 for Substance Use Disorders, six for Neurocognitive Disorders, and 18 for Neurodevelopmental Disorders (specifically, Attention-Deficit/Hyperactivity Disorder, ADHD), in addition to three for Psychiatric Medication-Related Movement Disorders. It is important to note that 37 out of the 118 medications were New Drug Application (NDA) approvals by the FDA, i.e., they have not been previously approved for another indication. We also noted that nine medications were discontinued by the manufacturer, with no reported safety or effectiveness concerns. Over the past fifteen years, several novel treatment approaches and modalities have been introduced, such as monoclonal antibodies for the treatment of Alzheimer’s Disease, very long-acting injectable antipsychotic drugs, targeting the glutamate neurochemical system for depression and depressive symptoms in other disorders, medications for conditions without any previously approved medicines (e.g., Binge Eating Disorder), and tablets with sensors to monitor treatment adherence. Of note, no new medications were approved from 2008-2023 for: Anxiety Disorders (with the exception of two extended-release preparations of previously approved agents), Obsessive-Compulsive Disorder, Trauma- and Stressor-Related Disorders, Dissociation Disorders, Somatic Symptom Disorders, and Disruptive, Impulse-Control, and Conduct Disorders. Conclusion: Approved psychiatric medications from 2008-2023 show substantial promise in the treatment of psychiatric conditions. More than 100 psychiatric medications were approved over the past 15 years for the major psychiatric conditions including a combination of newly introduced medications and new indications and drug formulations for already approved medications. It behooves psychiatric clinicians to keep up to date with this ever evolving and fast changing field. As the overview article, this manuscript will be followed by in-depth, disorder-based descriptions of approved medications, as well as those currently under development in Phase III.

Physicochemical compatibility of caffeine citrate and caffeine base injections with parenteral medications used in neonatal intensive care settings

PurposeTo investigate the physicochemical compatibility of caffeine citrate and caffeine base injections with 43 secondary intravenous (IV) drugs used in Neonatal Intensive Care Unit (NICU) settings.MethodsCaffeine citrate (20 mg/mL or 10 mg/mL) or caffeine base injection (10 mg/mL) were mixed in a volume ratio of 1:1 with the secondary drug solution to simulate Y-site co-administration procedures in NICUs. Physical compatibility was evaluated based on visual observation for 2 h, against a black and white background and under polarised light, for changes in colour, precipitation, haze and evolution of gas. Chemical compatibility was determined from caffeine concentration measurements, using a validated high-performance liquid chromatography assay.ResultsSix of the 43 secondary drugs tested (aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine) were physically incompatible with caffeine citrate undiluted injection (20 mg/mL), at their high-end, clinically relevant concentrations for NICU settings. However, when tested at lower concentrations, hydrocortisone (1 mg/mL) was physicochemically compatible, whereas furosemide (0.2 mg/mL) was physically incompatible with caffeine citrate. The six drugs which showed physical incompatibility with caffeine citrate 20 mg/mL injection were also physically incompatible with caffeine citrate 10 mg/mL solution. All 43 secondary drugs tested were physicochemically compatible with caffeine base injection.ConclusionsMost secondary test drugs, except aciclovir, amphotericin (liposomal), furosemide, hydrocortisone, ibuprofen and ibuprofen lysine, were physicochemically compatible with caffeine citrate injection. Caffeine base injection was physicochemically compatible with all 43 test drugs tested.

Monitoring Progress Towards the Elimination of Hepatitis C as a Public Health Threat in Norway: A Modelling Study Among People Who Inject Drugs and Immigrants.

The global incidence target for the elimination of hepatitis C among people who inject drugs (PWID) is <2/100. In Norway, the hepatitis C epidemic is concentrated in PWID. Immigrants are the second most important risk group for chronic infection. We modelled the incidence of hepatitis C among active PWID, and the prevalence of chronic infection among active PWID, ex-PWID, and immigrants in Norway to 2022. We built a stochastic compartmental model, which was informed using data from national data sources, literature, and expert opinion. We report median values with 95% credible intervals (CrI). The model estimated 30 (95% Crl, 13-52) new infections among active PWID in 2022, or 0.37/100 (95% Crl, 0.17-0.65), down from a peak of 726 (95% Crl, 506-1067) in 2000. Across all groups, the model estimated 3202 (95% Crl, 1273-6601) chronically infected persons in 2022. Results were robust in sensitivity analyses. Norway provides an example of the feasibility of hepatitis C elimination in a setting with a concentrated epidemic, high coverage of harm reduction services, and no treatment restrictions. Continued momentum is needed to further reduce the transmission and burden of hepatitis C in Norway.

Design and Synthesis of New GS-6207 Subtypes for Targeting HIV-1 Capsid Protein.

HIV-1 capsid protein (CA) is the molecular target of the recently FDA-approved long acting injectable (LAI) drug lenacapavir (GS-6207). The quick emergence of CA mutations resistant to GS-6207 necessitates the design and synthesis of novel sub-chemotypes. We have conducted the structure-based design of two new sub-chemotypes combining the scaffold of GS-6207 and the N-terminal cap of PF74 analogs, the other important CA-targeting chemotype. The design was validated via induced-fit molecular docking. More importantly, we have worked out a general synthetic route to allow the modular synthesis of novel GS-6207 subtypes. Significantly, the desired stereochemistry of the skeleton C2 was confirmed via an X-ray crystal structure of the key synthetic intermediate 22a. Although the newly synthesized analogs did not show significant potency, our efforts herein will facilitate the future design and synthesis of novel subtypes with improved potency.