Intravenous Drug Research Articles

Heartfelt Impact: A Descriptive Analysis of Ceftaroline-Containing Regimens in Endocarditis due to Methicillin-Resistant Staphylococcus aureus.

Infective endocarditis (IE) due to methicillin-resistant Staphylococcus aureus (MRSA) is characterized by frequent treatment failure to first-line agents and high mortality, necessitating use of alternative management strategies. Ceftaroline fosamil (CPT) is a cephalosporin antibiotic with activity against MRSA but without regulatory approval for the indication of IE. This study describes clinical experience with CPT-based regimens utilized in MRSA-IE. This is a retrospective, observational, descriptive analysis of patients from two major urban medical centers in Detroit, Michigan from 2011 to 2023. Included adult patients (≥ 18years) had ≥ 1 positive blood culture for MRSA, met definitive clinical criteria for IE, and received CPT for ≥ 72h. The primary outcome was treatment failure, defined as a composite of 30-day all-cause mortality from index culture or failure to improve or resolve infectious signs/symptoms after CPT initiation. Seventy patients were included. The median (interquartile range [IQR]) age was 51 (34-63) years and 45.7% were male. Persons with injection drug use (PWID) made up 55.7% of the cohort and right-sided IE was the most prevalent subtype (50.0%). CPT was frequently employed second-line or later, often in combination with vancomycin (10.0%) or daptomycin (72.9%). Overall, 31.4% experienced treatment failure and 30-day all-cause mortality occurred in 15.7%. These findings illustrate the challenges posed by MRSA-IE, including frequent treatment failures, and highlight the utilization of CPT as salvage therapy. Comparative studies are needed to more clearly define its role in MRSA-IE.

Perceived patient navigator services and characteristics to address barriers to linkage to hepatitis C care among people released from provincial prison in Quebec, Canada

BackgroundPatient navigation increases linkage to hepatitis C virus (HCV) care following release from prison; however, little is known about the services patient navigators should provide to maximize linkage to care. We aimed to identify perceived barriers and facilitators to linkage to HCV care post-release, and to determine patient navigator services and characteristics best suited to address barriers to linkage to care among people released from prison. MethodsTen semi-structured interviews were conducted with adult (age ≥ 18 years) men living with chronic HCV, released from the largest Quebec provincial prison, and linked to HCV care by a patient navigator. Interviews were guided by the Socio-Ecological Model (SEM) and aimed to explore the multi-level barriers and facilitators to linkage to HCV care post-release. Interviews were audio-recorded, transcribed, and analyzed using a deductive, thematic approach. ResultsThe median age of participants was 54 years. Barriers to linkage to HCV care included competing priorities post-release (e.g., substance use, mental health issues, unstable housing), stigma (related to HCV, injection drug use, and incarceration), and lack of transportation. Facilitators included social support, established relationships with existing healthcare providers, prior cure with direct-acting antivirals, and HCV-related health literacy and knowledge. Perceived essential patient navigator services to enhance linkage included pre-release discharge appointments, housing assistance, and facilitated transportation to HCV appointments. Ensuring a consistent, non-judgemental, and empathetic patient navigator were considered important characteristics; lived experiences of incarceration and/or HCV were not felt to be essential for a patient navigator. ConclusionsInterventions that seek to improve linkage to HCV care for people following release from prison should address many levels (individual, interpersonal, and policy) of the SEM. While people experience several competing priorities post-release, having an empathetic and consistent patient navigator, regardless of their lived experiences of HCV and/or incarceration, may improve linkage to HCV care post-release.

Current Trends in HIV Infection in the Republic of Crimea

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection.

Characteristics of attrition within the SuperMIX cohort of people who inject drugs: a multiple event discrete-time survival analysis

BackgroundCompared to the general population, people who inject drugs have poor health and wellbeing. Longitudinal studies can provide insight into factors driving these worse health outcomes but are subject to methodological challenges, such as cohort attrition. The aim of this study was to assess and characterise attrition in a prospective cohort of people who inject drugs in Victoria, Australia.MethodsUsing annually collected self-reported data from The Melbourne Injecting Drug User Cohort Study (SuperMIX) from September 2008 to January 2021, we estimated the incidence of participants being lost-to-follow-up (LTFU), with an episode of being LTFU defined as participants not undertaking a follow-up interview within two years of their last interview. We utilised a multiple event discrete-time survival analysis on participant period-observation data to estimate the associations between key factors and LTFU. Key areas of exposure measurement in analyses were sociodemographic, drug use and mental health.ResultsA total of n = 1328 SuperMIX participants completed a baseline interview, with n = 489 (36.8%) LTFU, i.e. not completing a follow-up interview in the following two years. Increased attrition was observed among SuperMIX participants who were: born outside Australia, younger than 30 years, reporting having completed fewer years of education, not residing in stable accommodation, not in stable employment and not on opioid agonist therapy (OAT).ConclusionsThe attrition rate of the SuperMIX cohort has largely been stable throughout the duration of the study. Higher attrition rates among individuals at greater sociodemographic disadvantage and not on OAT suggest that additional efforts are required to retain these participants. Findings also suggest that SuperMIX might not be capturing data on adverse health and wellbeing outcomes among subpopulations at high risk of harm.

A rare cutaneous manifestation of systemic sclerosis

A 43-year-old male with a history of intravenous drug use and alcohol consumption presented to the emergency department with three-month history of failure to thrive. The patient exhibited a constellation of constitutional symptoms including cough, weight loss, fatigue, decreased appetite, nausea and vomiting. The skin examination revealed multiple subcutaneous hyperpigmented, indurated plaques and nodules on the trunk and arms. Laboratory evaluation revealed abnormal autoimmune tests, anaemia, elevated inflammatory markers and radiological evidence of interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). An excisional biopsy from a skin lesion demonstrated dermal sclerosis consistent with scleroderma. The patient was diagnosed with diffuse systemic scleroderma with cutaneous findings consistent with nodular or keloidal scleroderma variant. This case highlights a rare cutaneous variant of systemic scleroderma called nodular or keloidal scleroderma.

Bipolar disorder in people with HIV: A nationwide, population-based matched case-control and matched cohort study.

To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings. Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts. Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios (HRs) among PWH for bipolar disorder and receipt of lithium. We included 5322 PWH and 53,220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection (aOR: 1.9, 95% confidence interval (CI): 1.2-3.0), especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (HR: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder, but not to the same degree as PWH and not of receipt of lithium. Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.

Cost-effectiveness of oral versus injectable disease modifying therapies in relapsing multiple sclerosis: a systematic review analysis

BackgroundMultiple sclerosis (MS) is a chronic and progressive neurological autoimmune disease that affects the central nervous system. There are two types of drugs used to treat this disease: injectable and oral drugs. The present study aimed at systematically reviewing the cost effectiveness of oral versus injectable drugs.MethodsThe researchers searched the PubMed, Scopus, and Web of Science databases to find relevant studies. After removing the duplicates, two authors independently assessed the records. The studies that had conducted full economic evaluations of oral versus injectable drugs in MS patients were included. The Quality of Health Economic Studies (QHES) tool was also used to assess the quality of the studies.ResultsThirty studies that had conducted the economic analysis of oral versus injectable therapies in MS patients were included in this review. The QHES scores for all records were generally high (≥ 77) and they were of good quality. The lowest and highest levels of incremental net monetary benefit were respectively obtained through the comparison of Fingolimod and Alemtuzumab (-1,419,333) and the comparison of Teriflunomide and Interferon β-1a (1,792,810). The amount of INMB (incremental net monetary benefit) in the comparisons between oral and injectable drugs showed that the highest and lowest amount of INMB calculated between) Fingolimod and injectable drugs, respectively, compared to (interferon β-1a) 98,253 and (Ocrelizumab) -212,417, the highest amount in dimethyl fumarate is also against (peginterferon β-1a) 191,470 and the lowest against (alemtuzumab) -124,333, Teriflunomide against injectable drugs is the highest against (peginterferon β-1a) 89,956 and the lowest (Ocrelizumab) − 194,169, as well as Cladribine compared to injectable drugs, the highest was compared to (interferon β-1a) 236,430 and the lowest (Ocrelizumab) was 23,965.ConclusionA large number of health economic evaluations of disease-modifying therapies (DMTs) in MS were available at the international level, the comparison of which was difficult and sometimes contradictory. However, despite the difference in the results, Cladribine tablets were cost-effective in all studies compared with injectable drugs. In addition, the present study could be of great importance for policymakers and other beneficiaries regarding the cost-effectiveness of the aforementioned drugs.

Drug-use-associated infective endocarditis in Denmark

Abstract Introduction Infective endocarditis (IE) has high mortality and the incidence is rising. Intravenous drug use is a risk factor for IE and poses challenges in clinical care. Amid the opioid crisis in many countries, rates of drug-use-associated IE (DU-IE) are increasing. While drug use in Denmark has remained stable the last decade, little is understood about the features and prognostic impact of DU-IE in developed nations not facing a current opioid crisis. Further, with multiple preventive measures deployed in local Danish regions, data on the evolution of DU-IE are warranted. Purpose To examine the temporal evolution, baseline characteristics, and long-term rates of all-cause mortality and IE recurrence in patients with DU-IE compared with patients with non-DU-IE. Methods This nationwide cohort study identified all first-time IE-patients (1999-2018) and categorized them in 1) patients with DU-IE, and 2) patients with non-DU-IE. Drug use was defined using ICD-8/10 codes or treatment for opioid use disorder. Patients were followed from the date of discharge, and absolute one-year rates of mortality and IE recurrence were examined with Kaplan-Meier estimates and the cumulative incidence function, respectively. Outcomes were compared with a multivariable adjusted Cox model. Results We identified 8,843 patients with IE: 407 (4.6%) with DU-IE (61% male, median age 44 years) and 8,436 (95.4%) with non-DU-IE (66% male, median age 72 years). While the absolute number of DU-IE increased, the proportion of DU-IE decreased from 5.9% in 1999-2003 (n=87) to 3.8% in 2014-2018 (n=114). Patients with DU-IE had a higher proportion of bloodstream infection with Staphylococcus aureus (49.4% vs 26.7%, p<0.001); conversely, they had a lower proportion of bloodstream infections with Streptococcusspecies (14.4% vs. 26.2%, p<0.011). Patient with DU-IE had lower in-hospital mortality compared with non-DU-IE (15.5% vs. 20.9%, p<0.001). Among those surviving admission, the one-year cumulative incidence of all-cause mortality was 16.9% in DU-IE and 17.3% in non-DU-IE (p=0.82), yet in adjusted analysis, DU-IE was associated with a higher one-year mortality rate (HR 1.64 [95% CI:1.23-2.21]) (Figure). The one-year cumulative incidence of IE recurrence was 12.8% in DU-IE and 4.3% in non-DU-IE, which corresponded to an adjusted HR of 3.39 (95% CI:2.35-4.88) in DU-IE. Conclusion While an increase in the absolute number of patients with DU-IE was observed, the proportion among all IE-patients was on the decline in Denmark until 2018—which contrasts with other countries where physicians currently battle collateral damage of the opioid crisis. Although drug use was associated with lower in-hospital mortality, it was striking that even though patient with DU-IE was almost 30 years younger, they still had higher rates of all-cause mortality and a more than three-fold increase in IE recurrence one year following discharge.

Microdosing of alteplase leads to thrombolysis in an in vitro flow model of cardiac microvascular obstruction

Abstract Background Cardiac microvascular obstruction (MVO) is a frequent injury of the myocardial microcirculation after successful recanalisation of the occluded coronary artery in myocardial infarction. At least in part, MVO is caused by embolised microthrombi of less than 200 µm diameter [1]. MVO leads to hypoperfusion of the myocardium and negatively affects patient outcomes. However, there is no effective treatment for MVO [2, 3]. Thrombolytic drugs are a promising approach, but they are difficult to deliver to the MVO area, and an increased risk of bleeding limits their use. In a previous study using an in vitro fluidic multi-scale model for MVO [4, 5], it was shown that controlled flow infusion (CFI) with a novel drug-delivering catheter could be used to effectively deliver highly concentrated intracoronary microdoses of a thrombolytic drug to the MVO area [6]. We now aim to investigate how such locally administered drug microdoses can induce thrombolysis as a possible therapeutic approach for MVO treatment. Methods A microfluidic chip (Fig.1) was used to study thrombolysis under flow using different microdoses of the thrombolytic drug alteplase. The chip consists of a tapered straight channel, which traps injected porcine microthrombi without causing complete channel occlusion (Fig. 1A). To mimic intracoronary CFI (consisting of temporary balloon occlusion of a coronary vessel for 90 seconds while drug is injected distally through a catheter) in vitro, microthrombi were incubated (without flow) directly in the chip for 90 seconds with various microdoses of alteplase (Fig. 2A, C). The chip was subsequently perfused with porcine plasma for 25 min (matched for physiological shear stress of 30 dyn/cm²). Conventional intravenous (IV) drug infusion (10 mg dose) resulting in a low systemic alteplase concentration, was mimicked by perfusing microthrombi with porcine plasma containing 2 µg/ml alteplase (Fig. 2B, C). Results Thrombolysis after CFI was concentration dependent, with the lowest microdose (0.3 mg) achieving 24% lysis of the thrombus area and the highest microdose (1.5 mg) achieving 60% lysis. In contrast, conventional IV drug infusion (corresponding to 10 mg alteplase IV dose) only achieved 10% lysis and was not significantly higher than the control perfused with pure porcine plasma. Conclusion Our findings suggest that intracoronary CFI is more efficient at achieving porcine microthrombus lysis than the current standard of IV bolus infusion (2 µg/ml alteplase in the circulating blood). Intracoronary CFI microdosing of fibrinolytic drugs using a drug-delivering catheter is a promising therapeutic approach for treating embolising MVO with a reduced systemic drug burden. Importantly, our intracoronary CFI approach achieves locally 6–40 times higher drug concentrations than a conventional IV drug infusion while reducing the total drug dose 60–300 times (Fig. 2C).

The Waiting 4 Surgery study: burden of in-hospital care

Abstract Introduction Patients with coronary artery and valvular diseases with surgical indication represent a significant proportion of hospitalizations. The Waiting 4 Surgery study (W4S) aims to better study this group of patients, their burden of hospital care and identify those with event-free admissions. Purpose In this work, we analyze both the economical and hospital-care burden of this group of patients. Methods Retrospective study of consecutive patients admitted between 2019 and 2021 with coronary artery and/or aortic valve diseases waiting for coronary artery bypass graft (CABG), aortic valve replacement (AVR; surgical or percutaneous) or both. Total admission time and the cost associated with the hospitalization were analyzed. For event-free hospitalization, the following events were considered: death, re-infarction, cardiac pulmonary arrest (CPA), stroke, ventricular tachycardia, acute heart failure (AHF), rest chest pain and reintroduction of intravenous (IV) drugs. We performed a secondary cost analysis for patients with event-free hospitalization after the first 5 days of admission. Results Total of 184 patients were included, mean age 67.9 years, 70.1% male, 71.2% submitted to CABG and 20.7% to AVR (6.5% to both). During admission 23.9% of patients reintroduced IV drugs, 20.1% had chest pain, 5.4% had AHF and 2.2% had CPA. No deaths, strokes of re-infarctions were observed. The total time of hospitalization was 3 259 patients/days, representing an occupation rate of 18.6% and a total cost of 1 898 447€ (10 318€/patient and 632 816€/year). Mean admission time was 17.6 days. Total cost for CABG and AVR patients was 1 479 613€ and 594 562€, respectively. Total of 115 patients had an event-free hospitalization (62.5%). The total time of event-free hospitalization was 1 650 patients/days, representing an occupation rate of 9.42% and a total cost of 979 710€ (6 575€/patient and 326 570€/year). Mean event-free admission time was 14.3 days. Total cost for CABG and AVR in event-free patients was 863 155€ and 223 258€, respectively. Conclusion The W4S study demonstrates the impact patients waiting for surgery represent in hospital care: a very high economic and logistic burden. The majority of patients showed an event-free admission, and identifying such patients for early discharge and ambulatory management together with surgical centers should be a priority.

Efficacy and safety of ultrasound guided stellate ganglion block: developing new clinical indications beyond electrical storm

Abstract Background Percutaneous stellate ganglion block (PSGB) is recommended by the latest European guidelines for patients with drug and ventricular tachycardia (VT) ablation refractory electrical storm (ES). Yet, due to the strong antiarrhythmic potential, combined with the good safety profile, we’ve recently used it for to the prophylaxis of ventricular arrhythmias (VAs) in high-risk patients and the prophylaxis/treatment of atrial arrhythmias in patients with acute heart failure (HF). Purpose To describe our single-center experience with PSGB usage outside the conventional indication of ES. Methods We hereby describe our single center experience with PSGB from 2/2021 to 2/2024. Results 56 patients (87% male, mean age 64 ± 12 years) received a total of 91 PSGB performed with the lateral, ultrasound (US) guided technique. Most of the procedures consisted of a single bolus anesthetic injection of lidocaine plus ropivacaine, 27% in an additional continuous infusion, mainly with ropivacaine. All procedures except for 3 in a single patient who had previously received left cardiac sympathetic denervation, were performed on the left side. Most of the patients (61%) suffered ischemic cardiomyopathy (CMP), including 11 with an acute coronary syndrome; the rest had non-ischemic CMP. 63 PSGB (69%) were performed in patients with impending or manifested cardiogenic shock (SCAI classification B or more). Mean LVEF was 24 ± 12%. Most of the procedures (n=80, 88%) were performed due to ongoing refractory VAs, yet 6 (6%) aimed to prevent major VAs in high-risk patients, mostly in the setting of recent ES (within 1 month) and need for Levosimendan to support cardiac output, in one case due to recent stereotactic VT ablation, to prevent early VAs in the phase of acute radiation induced microvascular damage. All 6 were effective in preventing clinically significant VAs. Additionally, 5 single bolus PSGBs (5%) were performed due to atrial arrhythmias with high ventricular rate despite intravenous drugs in the setting of acute HF. Specifically, 3 patients had atrial fibrillation (AF), 1 patient runs of ectopic atrial tachycardia (AT) and 1 patient 2:1 atrial flutter. Left-sided PSGB significantly reduced (≥25% reduction) ventricular rate during AF and AT but not during the single case of 2:1 atrial flutter, in 2/3 AF cases a cardioversion into sinus rhythm occurred within 40 minutes from PSGB. Only 1 (1%) major complication occurred (respiratory arrest), that was quickly and effectively treated with lipid emulsion, while minor complications were observed in 11% of PSGBs (mostly transient left arm weakness). Conclusions Our data suggest that US-guided PSGB usage, thanks to its feasibility at bed-side and good safety profile, may expand, beyond ES, to not only VAs prevention in high-risk settings, but also to prophylaxis/treatment of atrial arrhythmias in critically ill patients with acute heart failure requiring concomitant inotropic support.

Scoping Review of Pre-Exposure Prophylaxis and Post-Exposure Prophylaxis in HIV Prevention in Türkiye

Abstract Background Pre-Exposure Prophylaxis (PrEP) is a medical -antiretroviral- prevention method that reduces the risk of HIV transmission during sexual intercourse or injection drug use. Post-exposure prophylaxis (PEP) refers to taking medicine after risky exposure. The European Centre for Disease Prevention and Control (ECDC) has recommended the integration of PrEP into the existing HIV prevention packages since 2015. In Türkiye, first PrEP Guideline was published in 2022. The aim of this study is to evaluate the literature gap on the PrEP and PEP for HIV prevention research in Türkiye. Methods This study was conducted in October 2023. Searches were performed using the keywords ‘HIV, AIDS’ and ‘Pre-exposure prophylaxis, PrEP, Post-exposure prophylaxis, PEP’ in PubMed, Web of Science, Scopus, TRDizin, and Dergipark for all years. ‘Türkiye, Turkey, Turkish’ were added into the keywords in international indexes, without using country filters. Inclusion criteria were research on PrEP or PEP for HIV, research conducted in or using data from Türkiye, publications in English/Turkish. Exclusion criteria were non-HIV topics, non-Turkish data, non-English/Turkish publications. Lists were merged, duplicates were removed. Inclusion-exclusion criteria were conducted at title and abstract level. Full texts of the included articles examined for bibliometric characteristics, study types, and key results. Results 1014 publications yielded, 993 evaluated, and 17 fully reviewed. Four discussed Türkiye’s PrEP practices (2018-2023); three analyzed PEP regimens; three were reviews on PrEP/PEP in Türkiye (2016-2022). Two original research articles explored PrEP awareness among Türkiye’s men having sex with men (2022) and infectious disease physicians’ attitudes toward PrEP (2020). Studies showed gaps in PrEP information and service access. Conclusions There are limited studies published on PrEP and PEP in HIV prevention in Türkiye. This study highlights the need for local research on the topic. Key messages • Evaluation of Pre-Exposure Prophylaxis (PrEP) and Post-Exposure Prophylaxis (PEP) publications highlights gaps in HIV prevention research. • Limited literature on PrEP and PEP in HIV prevention emphasizing the need for further studies and improved access to PrEP information.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Substance use and risk behaviour patterns among people who inject drugs

Abstract Background Substance use and injecting drug use in particular are related to health damages, reduced quality of life and life expectancy. Injecting drug use is a risk factor for acquiring infectious diseases among people who inject drugs (PWID). The aim of the study was to assess the risk behavior related to the use of intravenous psychoactive substances among PWID in Lithuania. Methods In 2023 a cross sectional study using respondent driven sampling (RDS) of active intravenous drug users (n = 370) was conducted in 5 different sites across Lithuania. RDS is a sampling methodology based on peer-referral in underserved populations that cannot be sampled randomly. Descriptive statistical and regression analyses were conducted using SPSS 23.0. Results 78% of the sample were males, 22% - females. Age mean is 40.6 years, SD-7.7. The first injecting drug was used at the age of 18 (mode). 69% of PWID received drug dependance treatment at least once in life. 70% of the PWID in harm reduction services are also in the substitution therapy programmes. Fentanyl is the main substance for every second respondent which is injected 3 times a day and commonly used with alcohol (64%). 79% of PWID during the last injection used sterile needles and syringes. 45% of respondents reported overdosing during the last 12 months and half of all PWID had naloxone for death prevention. Nearly 70% were tested for TB and syphilis during the last 12 months. Conclusions PWID are mainly males who began injecting drugs at 18 years. Unsafe injecting behaviour (frequency and mode), using alcohol were related to lower participation in health care services for PWID. Main messages • Lower participation in health care services is related to behavioural risk factors. • Ongoing research is needed to assess the factors determining engagement into healthcare of PWID.

Hemodynamic effects of intra-aortic balloon pump in patients with advanced heart failure and cardiogenic shock waiting heart transplant

Abstract Background The use of intra-aortic ballon pump (IABP) as a bridge therapy in patients with advanced heart failure (HF) and cardiogenic shock (CS) waiting heart transplant (HTx) remains under debate. IABP can be an available device to improve hemodynamic conditions of these patients until HTx. Purpose Evaluate the hemodynamic effects of IABP and its efficacy in patients with advanced HF and CS waiting HTx. Methods We retrospectively analyzed from a single center intensive care unit, between 2009 and 2020, patients with advanced HF with optimized intravenous drugs that required IABP placement before HTx. Changes in oxygen central venous saturation (ScvO2), arterial lactate, renal function, and use of vasoactive drugs before and 96 hours after IABP insertion were evaluated. Patients with acute myocardial infarction and implant of ventricular assist device before HTx were excluded. Results A total of 199 patients (mean age 46,5 ± 12 years) were included. Median time of IABP onset to HTx was 20 days. Mean left ventricle ejection fraction was 23,5 ± 5,9%, 53,7% of patients had moderate to severe right ventricular dysfunction and the most frequent etiology was Chagas disease (47,2%, n=94). Before the IABP placement, 97,47% of patients were using dobutamine, 19,29% milrinone, 58,08% nitroprusside and 17,7% norepinephrine. Clinical and laboratory data were compared before and 96 hours after IABP therapy. ScvO2 increased from 49,9% to 66,85% (p<0,001), lactate decreased from 21,91 mg/dl to 12,6 mg/dl (p<0,001), creatinine decreased from 2,04 mg/dL to 1,72 mg/dL (p=0,301) and urine output increased from 1690,12 mL/24h to 2193,12 mL/24h (p<0,001). These differences were maintained until the day before HTx. Use of nitroprusside increased from 58,08 to 63,59% (p=0,154), and the use of norepinephrine decreased from 17,7% to 6,63% (p<0,001). Conclusion IABP improves tissue perfusion, renal function, and hemodynamic status in patients with advanced HF and CS and can be an effective method of circulatory support as a bridge therapy to HTx.Laboratory data pre and post-IABPVasoactive Drugs pre and post-IABP

Responsive Hydrogel-Based Drug Delivery Platform for Osteoarthritis Treatment

Osteoarthritis (OA) is the most prevalent chronic joint disorder and is a major cause of disability among the elderly population. The degeneration and damage of articular cartilage associated with OA can result in a diminished range of motion in joints, subsequently impacting fundamental activities such as ambulation, standing, and grasping objects. In severe cases, it may culminate in disability. Traditional pharmacological treatments are often accompanied by various side effects, while invasive surgical procedures increase the risk of infection and thrombosis. Consequently, identifying alternative new methods for OA treatment remains a formidable challenge. With advancements in responsive hydrogel drug delivery platforms, an increasing number of strategies have emerged to enhance OA treatment protocols. Injectable response hydrogel drug delivery platforms show many advantages in treating OA, including improved biocompatibility, prolonged drug release duration, elevated drug loading capacity and enhanced sensitivity. This article reviews the recent progress of injectable responsive hydrogel drug delivery platform for OA treatment over the past few years. These innovative methodologies present new strategies and directions for future OA treatment while summarizing a series of challenges faced during the clinical transformation of injectable response hydrogel drug delivery platforms. Overall, injectable responsive hydrogel drug delivery platforms show great potential in treating OA, especially regarding improving drug retention time and stimulus-responsive release at the lesion sites. These innovative methods provide new hope for future OA treatment and point the way for clinical applications.

"We're Not Gonna Aid You in Shooting Up": Stigma's Relationship to Harm Reduction in People Who Inject Drugs.

Harm reduction, when applied to drug use, prioritizes improving patient-centered health outcomes and reducing drug-related harm. In order for harm reduction strategies to be adopted by people who inject drugs (PWID), they need to be promoted, accessible, and accepted in that population and the community-at-large. While PWID face stigma at multiple levels, less is known about how stigma influences uptake and acceptance of harm reduction services and strategies among PWID. We aim to characterize the stigmatizing experiences PWID have had related to harm reduction and the role of stigma in influencing their acceptance and adoption of harm reduction services and strategies. A qualitative study using in-person, semi-structured interviews. We recruited hospitalized participants, age 18 and over, with a history of injection drug use. We developed an interview guide asking about various aspects of stigma and participants' experiences with naloxone, syringe service programs, fentanyl test strips, HIV and hepatitis C testing, and any other harm reduction strategies. Key themes were generated using a thematic analysis. We reached thematic saturation at 16 participants. PWID reported multi-level stigma related to harm reduction from themselves, the public, the healthcare system, and the legal and carceral systems. Themes were grouped into four main categories: internalized, interpersonal, intervention, and structural stigma. Stigma across all of these domains negatively impacted the ability of PWID to access harm reduction resources. Positive, non-stigmatizing experiences from others, such as syringe service programs and peer navigators, countered historically negative experiences and promoted greater education and comfort about using harm reduction resources among PWID. To expand the reach of harm reduction services, it is critical to develop interventions that can reduce the stigma against PWID and harm reduction.

Predictors of treatment outcomes for Hepatitis C infection in a nationwide elimination program in Iceland: The treatment as prevention for Hepatitis C (TraP HepC) study

BackgroundLimited data exists about treatment outcomes in nationwide hepatitis C virus (HCV) elimination programs where injection drug use (IDU) is the main mode of transmission. In 2016 Iceland initiated the HCV elimination program known as Treatment as Prevention for Hepatitis C (TraP HepC). Factors associated with HCV cure in this population are examined. MethodsUnrestricted access was offered to direct acting antiviral agents (DAAs). Testing and harm reduction was scaled up and re-treatments were offered for those who did not attain cure. Cure rates for the first 36 months were assessed and factors associated with failure to achieve cure analysed using multivariable logistic regression. ResultsTreatment was initiated for 718; 705 consented for the study. Median age was 44 years (IQR 35–56), history of IDU reported by 593 (84.1 %), recent IDU by 234 (33.2 %); 48 (6.8 %) were homeless. Of 705 patients, 635 achieved cure (90.1 %) during the first treatment. A total of 70 (9.9 %) patients initiated two or more treatments, resulting in 673 participants cured (95.5 %). By multivariable analysis, homelessness was the only statistically significant independent factor associated with not achieving cure (OR 2.67, 95 % CI 1.32–5.41) after first treatment attempt. ConclusionBy reengagement in care and prompt retreatment when needed, a cure rate of 95.5 % was achieved. Unstable housing, a potentially actionable factor is associated with poor outcome.

Impact of smoking habits on cardiovascular and neoplastic events and all-cause death in people living with HIVfrom the STOPSHIV cohort.

The study aimed to assess the impact of smoking exposure on major clinical events (MCE) in a real-life setting of people living with HIV (PWH). Observational longitudinal multicentre cohort study from Italy. Consecutive 983 PWH were enrolled in "STOP Smoking in HIV people" (STOPSHIV) projects and followed from July 2014 until September 2023. The observed MCE defined as cardiovascular (CV) events, neoplastic diseases or death for any reason was assessed according smoking status and related variables (number of cigarettes smoked daily, pack-years, Fagerström test) in participants. The association between exposure variables and the event was evaluated using the Cox proportional hazard model (hazard ratios, HR, and 95% CI). Over 6997.6 person-years of follow-up (PYFU), we found a total of 49 CV events, 61 neoplastic events, and 47 deaths. The overall incidence rate of MCE was 17.6 /1000 PYFU (95% confidence interval 14.7-21.0). All-cause death rate was 6.7 (95% CI 5.0-8.9)/1000 PYFU. In a multivariate analysis, older age (HR 1.07, CI 1.05-1.09), high Fagerström Test for Nicotine Dependence (HR 1.09, CI 1.03-1.15), a low nadir CD4 <200 cells/mm3 (HR 1.63, CI 1.10-1.41), history of previous neoplasm (HR 2.41; CI 1.34-4.43) and intravenous drug use as risk factor for HIV infection (HR 2.36; CI 1.52-3.68) were independent predictors of any MCE. Non-AIDS clinical conditions are the most observed clinical events in PWH from Italy. Smoking exposure significantly increases the risk of MCE in PWH and a high Fagerström Test for Nicotine Dependence is a predictor of MCE.

Locally Advanced Splenic Flexure Tumor With Invasion And Formation Of Splenic Abscess

Introduction: Splenic abscesses are rare, with an incidence of 0.14-0.70% in autopsies, affecting mainly men and immunosuppressed patients. Symptoms include fever, abdominal pain, nausea, and vomiting. Splenic invasion by colon cancer at the splenic flexure is uncommon. We report a case of cancer at the splenic flexure resulting in a splenocolic fistula and splenic abscess. Case Description: A 43-year-old man, with a history of injectable drug use, presented with diffuse abdominal pain. Tests revealed leukocytosis, thrombocytopenia, and elevated bilirubins and liver enzymes. A CT scan identified thickening in the colon and a splenic abscess. Total splenectomy and left colectomy with colon-colonic anastomosis were performed. Discussion: Splenic abscesses are rare and, when associated with colonic neoplasms, present a diagnostic and therapeutic challenge. This case highlights the importance of aggressive surgical intervention to treat tumor invasions and associated complications.