Search Results (32)

While direct-acting antivirals (DAAs) are available for the treatment of chronic Hepatitis C virus (HCV) patients in Nepal, knowledge of the circulating genotypes/subtypes and drug target gene mutations of HCV is currently unavailable. Here, we describe HCV genotypes/subtypes and identify antiviral target gene mutations in patients at a tertiary care hospital using genome data. A cross-sectional study was conducted from December 2019 to February 2024, where PCR followed by whole genome sequencing was performed to identify HCV genotypes/subtypes and drug target gene mutations. Among all the patients who tested positive for anti-HCV, 70.6% (149/211) were HCV RNA positive, while 68.2% (30/44) were genotype/subtype 3a, followed by 1a (18.2%, 8/44) and others (13.6%, 6/44), including new subtypes 3g and 3i from Nepal. Subtype 3a was also the dominant subtype (≥70%) among intravenous drug users and sexual routes of transmission. We found 70.5% of the samples with resistant mutations in the NS3/4A region, 22.7% in NS5A, and 45.5% in NS5B. Resistant mutations against sofosbuvir, pibrentasvir, velpatasvir, daclatasvir, and dasabuvir were found at 25%, 18%, 16%, 16%, and 2%, respectively, mostly on subtype 3a. The predominant HCV genotype/subtype in our patient group was 3a, and resistance mutations against direct-acting antivirals were found in most untreated patients. 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

Elimination of hepatitis C virus (HCV) without the need for medical intervention, known as spontaneous clearance (SC), occurs at a significantly lower rate than in the case of hepatitis B virus infection and only in selected individuals, such as reportedly in Keith Richards, a guitarist of The Rolling Stones. The present paper provides an updated narrative review of the research devoted to the phenomenon in order to identify and discuss the demographic, lifestyle-related, clinical, viral genotype-related, and host genetic factors underpinning the SC occurrence. The body of evidence indicates that the likelihood of SC is decreased in older individuals, men, Black people, HIV-coinfected subjects, and intravenous drug and alcohol users. In turn, HBV coinfection and specific polymorphism of the genes encoding interferon lambda 3 (particularly at rs8099917) and interferon lambda 4 (particularly at rs12979860) and HLA genes increase the odds of SC. Numerous other host-specific genetic factors could be implicated in SC, but the evidence is limited only to certain ethnic groups and often does not account for confounding variables. SC of HCV infection is a complex process arising from a combination of various factors, though a genetic component may play a leading role in some cases. Understanding factors influencing the likelihood of this phenomenon justifies better surveillance of high-risk groups, decreasing health inequities in particular ethnic groups, and may guide the development of a prophylactic vaccine, which at present is not available, or novel therapeutic strategies. Further research is needed to elucidate the exact mechanisms underlying SC and to explore potential interventions that could enhance this natural antiviral response. Full article

The objective of this study was to analyze the epidemiological links of the human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV-HCV coinfections to less studied types of transmission in certain populations. We performed an observational, prospective study on 903 patients aged between 15–87 years who took part in the Open Test Project. They were divided in two subgroups: general population vs. individuals from prisons who were questioned about multiple risk factors. A chi-square independence test was used to establish correlations between risk factors and results of screening tests. Logistic regression was used to calculate the probability of a reactive screening test based on each independent risk factor and age. HIV was very strongly associated with unprotected sexual intercourse with HIV-positive partners (the strongest association), unprotected sexual intercourse with sex workers, newly diagnosed sexually transmitted diseases (STDs), intravenous drug users (IDUs) and sharing injecting materials. In the case of HCV reactive tests, very strong associations have been established with IDUs (the strongest association), unprotected sex with IDUs and sharing injecting materials. Our study indicates the need for implementing targeted public health programs, tailored to the local epidemiology that can ultimately lead to micro-elimination of hepatitis and HIV infections in this area. Full article

A serological screening was conducted to detect IgG antibodies against Leishmania infantum (L. infantum) in newly diagnosed human immunodeficiency virus (HIV) patients in Greece. The study also examined potential risk factors and the agreement of commercially available serological methods. IgG antibodies against L. infantum were detected using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence antibody test (IFAT), and Western blot (WB). Out of 155 samples, 14 (9.0%) tested positive for IgG antibodies against L. infantum using at least two methods. Statistical analysis showed substantial agreement between WB and IFAT methods (Cohen’s kappa = 0.75) but moderate overall agreement among the three methods (Fleiss’ kappa = 0.42). Additionally, HIV+ intravenous drug users faced 3.55 times (p = 0.025) higher risk of testing positive for L. infantum IgG, positing that anthroponotic transmission between these patients is a plausible hypothesis based on existing literature. Non-invasive and cost-effective techniques are preferred to detect asymptomatic infections, and leishmaniasis screening should be conducted immediately after HIV diagnosis in endemic regions to enable prophylactic treatment for leishmaniasis in addition to antiretroviral therapy. To maximize sensitivity, performing at least two different serological methods for each patient is recommended. Full article

Intravenous therapy is the standard medical procedure that is used for administering medications directly into the vein. The automated drug infusion devices are designed in such a way that they provide exact medication doses with safety measures included. On the other hand, this is why they must be regularly watched by healthcare providers. This paper introduces a cloud-based IoT drug infusion system that was developed to address remote patient care needs. This system enables remote, accurate, and secure management of medication delivery. Its key contributions include allowing healthcare providers to control and monitor IV infusions remotely while maintaining safety features. The system consists of a microcontroller that is responsible for data processing, a control system that oversees infusion rate regulation, and an IoT-based framework that allows for remote monitoring and alerts via a user-friendly web interface. This new approach to care will therefore improve patient care by providing remote management of medications. Full article

Pharmaceutical opioids are intravenously or orally administered analgesics. While they are effective in relieving chronic and acute pain, their narrow window of therapeutic use contributes to the high occurrence of abuse. The associated abuse of this family of drugs can be correlated to the increase in dependency, overdose, and death of users. The negative effects of opioids extend beyond the physical and psychological effects experienced by the user to their unregulated synthesis and sale, which contribute to socioeconomic challenges and are a biproduct of this global public health epidemic. From clinical to point-of-care applications, the detection and real-time monitoring of this family of drug is critical in the fight to decrease abuse and improve use in clinical settings. Chromatographic separations and chromatography–mass spectrometry are traditional methods of opioid analyses, but the high cost, long analysis time, and absence of portability highlight the need for the development of fast, in situ, point-of-care analysis, or of community drug monitoring services. This review highlights recent electrochemical and optical (FTIR, Raman, colorimetric, and fluorescent) advances and biosensors for pharmaceutical and illicit opioid analysis. Specifically, an emphasis is placed on the detection of opioids and their metabolites in biological samples and in vitro cellular assays for clinical diagnosis and forensic applications. The challenges and prospects of the role of electrochemical sensors, biosensors, and optical sensors for opioid analysis in promoting clinical diagnosis, forensic study, point-of-care, and community drug monitoring services to reduce harm are also provided. Full article

Introduction: Synthetic cathinones are a group of novel psychoactive substances used as an alternative to classical recreational drugs. As a result of legal prohibitions on older generations of these compounds, new formulations appeared on the drug market. One of them is metaphedrone (3-methylmethcathinone, 3-MMC), a structural isomer of 4-methylmethcathinone and a psychostimulant drug. Metaphedrone became popular in a large number of countries in a short period of time. The aim: The collection, analysis, and review of relevant research on the subject of metaphedrone in order to present information about the pharmacological, clinical, and toxicological profile of this compound. An assessment of the significance and role of metaphedrone in consumption patterns of novel psychoactive substances among recreational drug users. Methodology: By using search engines like Google Scholar and PubMed, the relevant literature on metaphedrone was looked for and analyzed. The search was not limited to a specific period of time. All information regarding the compound of interest was analyzed and presented. Key results and discussion: All novel psychoactive substances are abused due to their pronounced stimulatory, hallucinogenic, dissociative, and euphoric and/or relaxing characteristics. Users of 3-methylmethcathinone usually opt for this substance for recreational purposes and/or sexual stimulation. Metaphedrone has the potential to cause a psychological dependence to the users. It was determined in relevant studies that most users are from 17 to 50 years of age. Older users usually administer metaphedrone intravenously, while younger ones usually choose snorting and oral ingestion of the drug. In Serbia, metaphedrone is a legally controlled substance. The pharmacodynamic properties make metaphedrone similar to classical recreational drugs. The method of administration, mainly repeated administration in a single session, could be explained using the pharmacokinetic profile of the drug. The most reported symptoms of intoxication were those of a sympathomimetic nature, such as tachycardia, chest pain, hypertension, diaphoresis, and agitation. Most intoxications and fatal outcomes occurred to users who combined several psychoactive substances. The correlation between measured blood concentrations of the drug and outcomes of intoxication was not found. The mechanisms of metaphedrone’s toxicity are not fully understood. Conclusions: There is an increasing trend of abuse of metaphedrone among recreational drugs users. Future studies should focus on pharmacological and toxicological effects of metaphedrone on animals and humans. Full article

Infective endocarditis (IE) is a severe cardiac complication with high mortality rates, especially when surgical intervention is delayed or absent. This review addresses the expanding role of surgery in managing IE, focusing on the variation in surgical treatment rates, the impact of patient demographics, and the effectiveness of different surgical approaches. Despite varying global data, a notable increase in surgical interventions for IE is evident, with over 50% of patients undergoing surgery in tertiary centres. This review synthesizes information from focused literature searches up to July 2023, covering preoperative to postoperative considerations and surgical strategies for IE. Key preoperative concerns include accurate diagnosis, appropriate antimicrobial treatment, and the timing of surgery, which is particularly crucial for patients with heart failure or at risk of embolism. Surgical approaches vary based on valve involvement, with mitral valve repair showing promising outcomes compared to replacement. Aortic valve surgery, traditionally favouring replacement, now includes repair as a viable option. Emerging techniques such as sutureless valves and aortic homografts are explored, highlighting their potential advantages in specific IE cases. The review also delves into high-risk groups like intravenous drug users and the elderly, emphasizing the need for tailored surgical strategies. With an increasing number of patients presenting with prosthetic valve endocarditis and device-related IE, the review underscores the importance of comprehensive management strategies encompassing surgical and medical interventions. Overall, this review provides a comprehensive overview of current evidence in the surgical management of IE, highlighting the necessity of a multidisciplinary approach and ongoing research to optimize patient outcomes. Full article

Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research. Full article

Hepatitis C (HCV) continues to present a global public health challenge, with no vaccine available for prevention. Despite the availability of direct-acting antivirals (DAAs) to cure HCV, it remains prevalent in many regions including the Caribbean. As efforts are made to eliminate HCV from the region, existing barriers, such as the high cost of DAAs and lack of an established database of HCV cases within the Caribbean, must be addressed. This review seeks to assess epidemiologic trends (seroprevalence and genotypic diversity) of HCV in the Caribbean and identify gaps in surveillance of the disease. The literature for the period 1 January 2005 to October 2022 was reviewed to gather country-specific data on HCV across the Caribbean. References were identified through indexed journals accessed through established databases using the following keywords: Caribbean, genotype distribution, and general epidemiologic characteristics. The usage pattern of HCV drugs was determined from information obtained from pharmacists across the Caribbean including Jamaica. The prevalence of HCV in the Caribbean was 1.5%; the region should therefore be considered an area of moderate HCV prevalence. The prevalence of HCV among intravenous drug users (21.9–58.8%), persons living with HIV/AIDS (0.8 to 58.5%), prisoners (32.8–64%), and men who have sex with men (MSM) (0.8–6.9%) was generally higher than in the general population (0.8–2.3%). Genotype 1 (83%) was most prevalent followed by genotypes 2 (7.2%) and 3 (2.1%), respectively. Less than 50% of countries in the Caribbean have reliable or well-curated surveillance data on HCV. Drugs currently being used for treatment of HCV infections across the Caribbean include Epclusa (sofosbuvir/velpatasvir) and Harvoni (ledipasvir/sofosbuvir). Some of these drugs are only available in the private sector and are sourced externally whenever needed. While trends point to a potentially higher prevalence of HCV, it will require well-designed random surveys to obtain better estimates of the infection seroprevalence, supported by strong public health laboratory systems. DAAs that are pan-genotypic should translate into treatments that are affordable, accessible, and available to improve cure rates and reduce the HCV burden in the population. Full article

Hepatitis C Virus (HCV) infection is a leading etiology of liver cirrhosis and its associated complications, namely, decompensated cirrhosis. As such, hepatitis C potentially necessitates liver transplantation and may result in death. Recently, HCV treatment has evolved. Current HCV treatment is effective in curing HCV; some of the agents are pan-genotypic. Numerous countries have adopted an initiative to eliminate HCV. Achieving elimination poses many challenges; it requires improved availability and accessibility of pan-genotypic therapy. Barriers exist at the level of the collective healthcare system and at the level of the individual healthcare providers and patients. Therefore, organized national and local efforts are needed. Surmounting these barriers calls for interventions concerning screening, linkage to care, and treatment delivery. Pertinent barriers include inadequate availability of screening, ill-equipped laboratory testing before treatment, and insufficient access to treatment. Interventions should seek to decentralize laboratory testing and treatment provision, increase funding for resources and personnel, and spread awareness. Special consideration should be allocated to at-risk populations, such as intravenous drug users, refugees, and prisoners. Computerized medical filing and telemedicine have the potential to refine HCV management by enhancing detection, availability, accessibility, and cost-effectiveness. Full article

Background: The care provided in general practice to intravenous drug users (IDUs) with hepatitis C (HCV) extends beyond opioid substitution therapy. An aggregated analysis of HCV service utilization within general practice specifically related to diagnosis and treatment outcomes remains unknown from previous literature. Aims: This study aims to estimate the prevalence of HCV and analyze data related to the diagnosis and treatment-related outcomes of HCV patients with a history of intravenous drug use in the general practice setting. Design and setting: A systematic review and meta-analysis in general practice. Methods: This review included studies published in the following databases: EMBASE, PubMed, and Cochrane Central Register of Controlled Trials. Two reviewers independently extracted data in standard forms in Covidence. A meta-analysis was done using a DerSimonian and Laird random-effects model with inverse variance weighting. Results: A total of 20,956 patients from 440 general practices participated in the 18 selected studies. A meta-analysis of 15 studies showed a 46% (95% confidence interval (CI), 26–67%) prevalence rate of hepatitis C amongst IDUs. Genotype information was available in four studies and treatment-related outcomes in 11 studies. Overall, treatment uptake was 9%, with a cure rate of 64% (95% CI, 43–83%). However, relevant information, such as specific treatment regimens, treatment duration and doses, and patient comorbidities, was poorly documented in these studies. Conclusion: The prevalence of HCV in IDUs is 46% in general practice. Only ten studies reported HCV-related treatment outcomes; however, the overall uptake rate was below 10%, with a cure rate of 64%. Likewise, the genotypic variants of HCV diagnoses, medication types, and doses were poorly reported, suggesting a need for further research into this aspect of care within this patient group to ensure optimal treatment outcomes. Full article

Hepatitis B virus infection occurs in approximately 7% of people living with HIV (PLWH), with substantial regional variation and higher prevalence among intravenous drug users. Early studies on the natural history of HIV/HBV coinfection demonstrated that in coinfected patients, chronic hepatitis B (CHB) has a more rapid progression than in HBV-monoinfected patients, leading to end-stage liver disease complications, including hepatocellular carcinoma. Therefore, the adequate management of CHB is considered a priority in HIV-coinfected patients. Several guidelines have highlighted this issue and have provided recommendations for preventing and treating HBV infection. This article discusses the management of liver disease in patients with HIV/HBV coinfection and summarizes the current and future therapeutic options for treating chronic hepatitis B in this setting. Full article

Molecular epidemiology of hepatitis C virus (HCV) is exceptionally complex due to the highly diverse HCV genome. Genetic diversity, transmission dynamics, and epidemic history of the most common HCV genotypes were inferred by population sequencing of the HCV NS3, NS5A, and NS5B region followed by phylogenetic and phylodynamic analysis. The results of this research suggest high overall prevalence of baseline NS3 resistance associate substitutions (RAS) (33.0%), moderate prevalence of NS5A RAS (13.7%), and low prevalence of nucleoside inhibitor NS5B RAS (8.3%). Prevalence of RAS significantly differed according to HCV genotype, with the highest prevalence of baseline resistance to NS3 inhibitors and NS5A inhibitors observed in HCV subtype 1a (68.8%) and subtype 1b (21.3%), respectively. Phylogenetic tree reconstructions showed two distinct clades within the subtype 1a, clade I (62.4%) and clade II (37.6%). NS3 RAS were preferentially associated with clade I. Phylogenetic analysis demonstrated that 27 (9.0%) HCV sequences had a presumed epidemiological link with another sequence and classified into 13 transmission pairs or clusters which were predominantly comprised of subtype 3a viruses and commonly detected among intravenous drug users (IDU). Phylodynamic analyses highlighted an exponential increase in subtype 1a and 3a effective population size in the late 20th century, which is a period associated with an explosive increase in the number of IDU in Croatia. Full article