Search Results (181)

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

The article analyzes the effects of psychosocial interventions on adherence to tuberculosis (TB) treatment among vulnerable populations in Romania. The study includes 4104 patients from disadvantaged groups (rural, injecting drug users, homeless), beneficiaries of a national multidisciplinary support program. Multivariate analyses conducted on drug-susceptible TB (DS-TB) patients within this cohort identified some predictors of therapeutic success, such as extrapulmonary diagnosis, peer-to-peer educational support, and a higher level of education. At the same time, men, occupationally inactive people and those in the initial phase of treatment at project entry showed lower adherence. The results support the integration of psychosocial interventions in TB management. Full article

Aboriginal and Torres Strait Islander people who inject drugs face persistent health inequities, highlighting the need for programs that meet the needs of these groups. This study explored how intersectional stigma and discrimination affect Aboriginal and Torres Strait Islander people’s access to quality healthcare. Aboriginal and Torres Strait Islander participants aged ≥18 years who had injected drugs within the past 12 months were recruited from two regional needle and syringe programs (NSPs) and a major city NSP in Queensland, Australia. Participants completed a structured survey and yarned with an Aboriginal researcher and non-Indigenous research assistant about their healthcare experiences. Through a process of reflexive and thematic analysis, three major qualitative themes emerged: participants’ social circumstances and mental health challenges made help-seeking difficult and complex; enacted stigma and racism diminished access to health services and the quality of care received; and injecting drug use was associated with disconnection from culture and community. Privileging the expertise and voices of those with lived/living experience is essential for the creation of culturally safe, inclusive, and destigmatising healthcare services for Aboriginal and Torres Strait Islander people who inject drugs. Full article

This study examines the trends, impacts, and challenges of HIV in Bangladesh from 2000 to 2024, with a focus on its epidemiology, demographic distribution, and socioeconomic determinants. Despite maintaining one of the lowest HIV prevalence rates globally (<0.1%), Bangladesh faces a concentrated epidemic among high-risk populations, including people who inject drugs (PWID), men who have sex with men (MSM), sex workers, transgender individuals, and migrant workers. Analysis reveals a steady increase in reported infections, attributed to enhanced diagnostic capacities and public awareness. The 25–49 year age group remains the most affected, accounting for over 65% of cases, underscoring the vulnerability of the economically active population. Gender disparities persist, with males representing the majority of infections but lower ART coverage among females and transgender individuals. While interventions such as PMTCT programs, ART expansion, and targeted awareness campaigns have contributed to improved outcomes, barriers such as stigma, healthcare inequities, and limited rural access hinder progress. The study also evaluates Bangladesh’s progress toward the 95-95-95 targets, highlighting significant strides in treatment and viral suppression but gaps in diagnosis. Future research must address behavioral trends, stigma reduction, and integration of HIV services for marginalized populations. This paper emphasizes the need for evidence-based strategies to ensure equitable healthcare delivery and sustainable progress in combating HIV. Full article

This study aimed to identify and synthesize the success metrics used to assess hepatitis C elimination among people who inject drugs (PWID) through harm reduction strategies. A scoping review was performed by searching across three databases to identify systematic reviews that discussed hepatitis C in PWID within the context of harm reduction. The studies were then analyzed for success metrics used to describe hepatitis C in PWID. The indicators used were prevalence, incidence, screening, treatment uptake, treatment completion, and sustained virologic response. A total of fourteen systematic reviews were included. The most frequently reported indicators were prevalence and incidence, addressed in eight/seven systematic reviews, respectively. In contrast, screening, treatment uptake, and treatment completion were less commonly reported, with only two reviews addressing screening and treatment uptake, and a single review reporting treatment completion. Similarly, sustained virologic response (SVR) was reported in only two systematic reviews. Seven additional indicators were reported. Prevalence and incidence are the dominantly used HCV indicators, while others are often neglected. Inconsistencies in measurements and reporting can be found for all indicators. This study reports a gap regarding indicators beyond prevalence and incidence, inconsistent measurement approaches, and a lack of standardized frameworks. Full article

Hepatitis C virus (HCV) remains a global health challenge, contributing to chronic liver disease and hepatocellular carcinoma. In Thailand, HCV prevalence has declined from ~2% in the 1990s due to universal blood screening, harm reduction, and expanded treatment. This narrative review draws on diverse sources—including PubMed and Scopus databases, international and national health websites, government reports, and local communications—to compile epidemiological data, genotype distribution, and elimination strategies, with a focus on Phetchabun province, Thailand, as a model for achieving the World Health Organization’s (WHO) hepatitis C elimination targets. National surveys in 2004, 2014, and 2024 show a prevalence drop from 2.15% to 0.56%. However, HCV persists among high-risk groups, including people who inject drugs, people living with HIV, patients undergoing maintenance hemodialysis, and prisoners. Thailand’s National Health Security Office has expanded treatment access, including universal screening for those born before 1992. The Phetchabun Model, launched in 2017, employs a decentralized test-to-treat strategy. By April 2024, 88.64% (288,203/324,916) of the target population was screened, and 4.88% were anti-HCV positive. Among those tested, 72.61% were HCV-RNA positive, and 88.17% received direct-acting antivirals (i.e., SOF/VEL), achieving >96% sustained virological response. The Phetchabun Model demonstrates a scalable approach for HCV elimination. Addressing testing costs, improving access, and integrating microelimination strategies into national policy are essential to achieving the WHO’s 2030 goals. Full article

Lipoprotein (a) [Lp(a)] has been recognized as an independent, inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, thus representing a major target of residual CV risk. Currently, no drug has been officially approved for lowering Lp(a) levels, and in clinical practice, Lp(a) is mainly used to (re)define CV risk, particularly in individuals at borderline CV risk and people with a family history of premature coronary heart disease, according to various guidelines. Specific Lp(a)-targeted antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) agents have been developed to produce substantial Lp(a) reductions via the inhibition of apo(a) synthesis in the liver. These drugs are conjugated to N-acetylgalactosamine (GalNAc) to ensure their binding to asialoglycoproteins, which are specifically expressed on the surface of the hepatocytes. Such drugs include pelacarsen (an injectable ASO) and olpasiran, zerlasiran, and lepodisiran (injectable siRNA agents). Muvalaplin represents another therapeutic option to lower Lp(a) levels, since it is an oral selective small molecule inhibitor of Lp(a) formation, thus potentially exerting certain advantages in terms of its clinical use. The present narrative review summarizes the available clinical data on the efficacy and safety of these investigational Lp(a)-lowering therapies, as reported in phase 1 and 2 trials. The effects of these drugs on other [aside from Lp(a)] lipid parameters are also discussed. The phase 3 CV trial outcomes are ongoing for some of these agents (i.e., pelacarsen, olpasiran, and lepodisiran) and are briefly mentioned. Overall, there is an urgent need for evidence-based guidelines on Lp(a) reduction in daily clinical practice, following the results of the phase 3 CV trials, as well as for establishing the ideal Lp(a) quantification method (i.e., using an apo(a) isoform-independent assay with appropriate calibrators, reporting the Lp(a) level in molar units). Full article

The number of people living with HIV in Kazakhstan increased from 11,000 to 35,000 between 2010 and 2021, with emerging antiretroviral therapy (ART) resistance posing a challenge to effective treatment. Unsafe injection practices among people who inject drugs (PWID), the stigma against men who have sex with men, sex work, drug possession, HIV transmission, HIV exposure, and the non-disclosure of HIV status create obstacles to effective prevention and care. Our recent studies with people living with HIV (PLWH) in Kazakhstan have revealed the prevalence of mutations in HIV that may confer resistance to certain ART components currently being administered in the country. Additionally, subtype A6- and CRF02_AG-infected PLWH displayed the occurrence of certain distinct subtype-specific DRMs. Subtype A6 exhibited a tendency for the DRMs A62V, G190S, K101E, D67N, and V77I, whereas CRF02_AG was more associated with S162A, K103N, and V179E. Both subtypes had a comparable frequency of the M184V mutation and displayed similar patterns in the distribution of Q174K. Based on our findings, we recommend that DRM screening and subtype diagnosis before the initiation of ART will improve treatment efficiency while preventing the emergence of further DRMs in Kazakhstan. Full article

Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions. Full article

Background/Objective: Cabotegravir (CAB), available as an oral tablet and as a long-acting (LA) nanosuspension for intramuscular injection, is approved as a combination therapy for the treatment, and as a monotherapy for the prevention, of HIV-1 infection. People living with HIV may receive multiple concomitant medications, with the associated risk of drug–drug interactions (DDIs). CAB is an inhibitor of OAT1/OAT3 renal transporters and a substrate of the UDP-glucuronosyltransferase enzymes UGT1A1 and 1A9, in vitro. While the effect of induction of UGT1A1/UGT1A9 on CAB exposure had been investigated in the clinic, the effect of the risk of DDIs with CAB via inhibition of these enzymes, or as an inhibitor of OAT1/OAT3 transporters, had not been evaluated. Methods: A physiologically-based pharmacokinetic (PBPK) model was developed and verified for orally dosed CAB to investigate the DDI risks associated with CAB, using a matrix approach to extensively qualify the PBPK platform and the substrates and/or inhibitors of either OAT1/OAT3 or UGT1A1/UGT1A9. The effect of uncertainties in in vitro inhibition values for OAT1/OAT3 was assessed via sensitivity analysis. Results: A mean increase of less than 25% in systemic exposure for OAT1/OAT3 substrates was predicted, with the potential for an increase of up to 80% based on the sensitivity analysis. On co-dosing with UGT1A1/UGT1A9 inhibitors, the predicted mean increase in CAB exposure was within 11%. Conclusions: PBPK modelling indicated that clinically relevant DDIs are not anticipated with OAT1/3 substrates or UGT1A1/1A9 inhibitors and CAB. With maximal exposure of the LA formulation of CAB being lower than the oral, the results of these simulations can be extrapolated to LA injectable dosing. Full article

Xylazine, commonly called “tranq” or “sleep cut”, is a strong α2-adrenergic agonist used in veterinary practice as a sedative, analgesic, and muscle-relaxing agent. It has never been approved by the Food and Drug Administration for human use, but its use by people is on the rise. In the last decades, due to its low cost and ease of availability, it has often been illicitly used due to its abuse potential as a drug for attempted sexual assault and intended poisoning. In addition, xylazine’s presence in the human body has also been related to domestic accidental events. Generally, it is combined with multiple other drugs, typically by intravenous injection, potentiating the doping effects. Xylazine’s mechanism of action is different from that of other illicit opioids, such as heroin and fentanyl, and it has no known antidote approved for use in humans. The combination with fentanyl prolongs the euphoric sensation and may heighten the risk of fatal overdose. Furthermore, it may cause adverse effects, including central nervous system (CNS) and respiratory depression, bradycardia, hypotension, and even death. Recent reports of xylazine misuse have risen alarmingly and describe people who become “zombies” because of the drug’s harmful effects on the human body, including serious wound formation that could even lead to limb amputation. This paper is an extensive review of the existing literature about xylazine and specifically deals with the chemistry, pharmacokinetics, pharmacodynamic, and toxicological aspects of this compound, highlighting the most recent studies. Full article

Globally, 50 million people are infected with hepatitis C virus (HCV), many of whom are people who inject drugs. These individuals face healthcare barriers, necessitating innovative diagnostic tools. This study evaluated the impact of cobas plasma separation cards (PSCs) for dry plasma collection in Barcelona’s outpatient drug addiction centers (CAS). From February to December 2021, nine CASs were invited to implement PSC for HCV screening; three centers participated, allowing for the assessment of its impact on HCV detection. Of the 679 clients screened, 54 (8%) provided finger-prick blood samples via PSC due to their refusal or inability to undergo venipuncture. Overall, 100 (14.7%) clients tested positive for HCV antibodies, with 24 (24%) confirmed as HCV-RNA positive. Among venipuncture clients, 9.1% had positive antibodies, with 15.8% showing active infection. In contrast, 79.6% of PSC clients had positive antibodies and 34.9% had detectable HCV RNA, contributing to 62.5% of the active infections detected. The odds ratio was 26.3, indicating that refusal or inability to undergo venipuncture correlated with a significantly higher burden of active HCV infection. The findings highlight PSC as a valuable alternative for diagnosing HCV in people with substance use disorders, addressing accessibility barriers and improving linkage to care in high-risk populations. Full article

The availability of highly effective direct-acting antivirals (DAAs) that cure individuals infected with HCV has changed completely the natural history of HCV infection and chronic hepatitis C. In sustained responders to DAAs, the most common clinical-pathologic outcome has become liver disease regression, cirrhosis re-compensation, and the de-listing of transplant candidates. However, careful scrutiny of liver disease cofactors and outcome predictors in treated patients is mandatory for an appropriate personalized surveillance of the residual risk for hepatocellular carcinoma. Since successful treatment with DAAs does not confer protective immunity against HCV reinfection, an effective vaccine is critically needed to control HCV infection. Meanwhile, it is mandatory to enhance universal access to DAAs, to test asymptomatic high-risk groups who are the main source of transmission, and to screen people who inject drugs (PWID), men who have sex with men (MSM), and sex workers, and to assure safe medical procedures with the provision of disposable needle and syringes. Full article

Background: Injecting drug use is a global public health challenge with multifaceted consequences, not only for people who inject drugs (PWIDs) but also for society at large. Their vulnerability necessitates a deeper exploration of their health information needs, aiming to leverage evidence-based research to shape effective interventions for their well-being. Method: This study employed a qualitative method to gain insights into disease conditions and health information needs of PWIDs. Through purposive and snowball sampling, 71 in-depth interviews were conducted and thematically analyzed. Results: This study included 43 males and 28 females, predominantly aged 26–35 (59.2%), who had low socioeconomic status. The most reported disease conditions varied and included malaria, infections, and diabetes. Findings revealed a complex understanding of their disease conditions and management practices. Participants emphasized a critical need for access to reliable and comprehensive health information, while also highlighting the significant barriers they face in obtaining this information. Additionally, their preference for receiving health information in video formats, written articles, and through outreach programs underscored their desire for knowledge to make informed decisions. As co-creators and stakeholders in their health, participants expressed a clear demand for sustainable and free healthcare, mosquito nets, and regular outreach programs. Conclusions: While drug use presents a significant public health issue, effective interventions for PWIDs require a multifaceted approach that begins with understanding their perspectives and actively involving them as co-creators of their health solutions. Abandoning this population contradicts the Sustainable Development Goals’ mandate to ensure no one is left behind. Thus, all stakeholders must prioritize inclusive and participatory approaches to address the complex health information needs of PWIDs. Full article

Highly effective direct-acting antiviral (DAA) therapies for hepatitis C (HCV) have been available in Australian prisons since 2016. To address treatment interruption following release from prisons, the Queensland Injector’s Health Network (QuIHN) launched a Prison Transition Service (PTS) in south-east Queensland, Australia. Presently, the factors associated with continuity of post-release HCV care are poorly understood. The objective of this qualitative study was to explore the barriers and facilitators to HCV treatment among people recently released from prisons among PTS clients and stakeholders. Qualitative interviews were conducted with 27 participants, namely, 13 clients and 14 stakeholders (health and community support workers) of the PTS. We conducted thematic analysis using the framework of person-, provider-, and system-level barriers and facilitators. Person-level barriers included competing priorities post-release, while facilitators included self-improvement after treatment completion, preventing transmission to family, and social support. Provider-level treatment barriers included enacted stigma, limited prison health service capacity, and post-release health system challenges. Systemic barriers included stigma relating to HCV, injecting drug use, incarceration, and limited availability of harm reduction services. Policy changes and investment are required to expand HCV treatment in south-east Queensland prisons to facilitate patient navigation into community care. In terms of reducing stigma among health staff and the general community towards people with HCV, a history of incarceration and/or who inject drugs is crucial for improving treatment rates. Strategies such as peer-led or nurse-practitioner-led models of care may help improve treatment completion. Continuity of HCV treatment post-release from prisons is essential for Australia to meet the WHO’s 2030 HCV elimination target. Full article