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Gold nanoparticles (AuNPs) are highly attractive for applications in the field of biosensing, particularly for colorimetric nucleic acid detection. Their unique optical properties, which are highly sensitive to changes in their environment, make them ideal candidates for developing simple, rapid, and cost-effective assays. When functionalized with oligonucleotides (Au-nanoprobes), they can undergo aggregation or dispersion in the presence of complementary sequences, leading to distinct color changes that serve as a visual signal for detection. Aggregation-based assays offer significant advantages over other homogeneous assays, such as fluorescence-based methods, namely, label-free protocols, rapid interactions in homogeneous solutions, and detection by the naked eye or using low-cost instruments. Despite promising results, the application of Au-nanoprobe-based colorimetric assays in complex biological matrices faces several challenges. The most significant are related to the colloidal stability and oligonucleotide functionalization of the Au-nanoprobes but also to the mode of detection. The type of functionalization method, type of spacer, the oligo-AuNPs ratio, changes in pH, temperature, or ionic strength influence the Au-nanoprobe colloidal stability and thus the performance of the assay. This review elucidates characteristics of the Au-nanoprobes that are determined for colorimetric gold nanoparticles (AuNPs)-based nucleic acid detection, and how they influence the sensitivity and specificity of the colorimetric assay. These characteristics of the assay are fundamental to developing low-cost, robust biomedical sensors that perform effectively in biological fluids.

Background: Hepatitis C (HCV) is a curable chronic infection, but lack of treatment uptake contributes to ongoing morbidity and mortality. State and national strategies for HCV elimination emphasize the pressing need for people with HCV to receive treatment., Objective: To identify provider-perceived barriers that hinder the initiation of curative HCV treatment and elimination of HCV in the USA., Approach: Qualitative semi-structured interviews with 36 healthcare providers who have evaluated patients with HCV in New York City, Western/Central New York, and Alabama. Interviews, conducted between 9/2021 and 9/2022, explored providers' experiences, perceptions, and approaches to HCV treatment initiation. Transcripts were analyzed using hybrid inductive and deductive thematic analysis informed by established health services and implementation frameworks., Key Results: We revealed four major themes: (1) Providers encounter professional challenges with treatment provision, including limited experience with treatment and perceptions that it is beyond their scope, but are also motivated to learn to provide treatment; (2) providers work toward building streamlined and inclusive practice settings-leveraging partnerships with experts, optimizing efficiency through increased access, adopting inclusive cultures, and advocating for integrated care; (3) although at times overwhelmed by patients facing socioeconomic adversity, increases in public awareness and improvements in treatment policies create a favorable context for providers to treat; and (4) providers are familiar with the relative advantages of improved HCV treatments, but the reputation of past treatments continues to deter elimination., Conclusions: To address the remaining barriers and facilitators providers experience in initiating HCV treatment, strategies will need to expand educational initiatives for primary care providers, further support local infrastructures and integrated care systems, promote public awareness campaigns, remove prior authorization requirements and treatment limitations, and address the negative reputation of outdated HCV treatments. Addressing these issues should be considered priorities for HCV elimination approaches at the state and national levels., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: This research aims to investigate the influence of environmental factors on the treatment efficacy of ocular lubricants in patients from urban areas with dry eye disease (DED)., Methods: A phase IV clinical trial, which included 173 patients from major cities in Mexico, was randomly assigned to use ocular lubricants four times a day for 30 days. Ocular Surface Disease Index (OSDI), noninvasive tear film break-up time (NIBUT), ocular staining, and conjunctival hyperemia (CH) among other factors like weather, and air pollution as covariates were analysed., Results: After 30 days, OSDI score decreased by 14.8 points ( p <0.001), and NIBUT increased by 2.9 seconds ( p < 0.001), with longer values observed in patients recruited in autumn and winter (additional 1.8 seconds, p < 0.05) compared to those recruited in spring. Patients living in cities with cooler weather and high humidity, but low air quality had higher OSDI and conjunctival stain scores of up to 4.4 and 0.3 points, respectively, as compared to those living in cities with similar pollution and humidity levels but with higher temperatures ( p -values= 0.019 and 0.050). Patients with moderate CH had an increase of up to 0.8 points in their corneal stain score ( p < 0.010). We also found that ozone levels were related to the predicted changes in OSDI and NIBUT., Conclusion: This study demonstrated the impact of environmental factors on the signs and symptoms of DED and suggests that patients residing in cities with inadequately controlled air pollution can benefit from using ocular lubricants to alleviate their symptoms., Trial Registration: Trial is registered at clinicaltrials.gov (NCT04702776)., Competing Interests: PMV, GGS, ROJF, SQJ, ASR and OOM are employees of Laboratorios Sophia, S.A. de C.V. The sponsor provided support in the form of salaries for the authors. This does not alter adherence to the Good Publication Practice guidelines for pharmaceutical companies (GPP3) policies on sharing data and materials. The authors report no other conflicts of interest in this work., (© 2024 Muñoz-Villegas et al.)

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers., (© 2024 John Wiley & Sons Ltd.)

The emergency department (ED) has increasingly become an important public health partner in non-targeted hepatitis C virus (HCV) testing and referral to care efforts. HCV has traditionally been an infection associated with the Baby Boomer generation; however, recent exacerbation of the opioid epidemic has resulted in a growing number of younger cohorts, namely Millennials, also impacted by HCV. Examination of this age-related demographic shift, including subsequent linkage success and linkage barriers, from the perspective of an ED-based testing and linkage programme may have implications for future population and health systems interventions. A retrospective descriptive chart review was performed, inclusive of data from August 2015 through December 2020. We compared the quantity of positive HCV screening antibody (Ab) and confirmatory (RNA) tests and further considered linkage rates and correlative demographics (e.g. gender, race). Patient barriers to HCV care linkage (e.g. substance misuse, lack of health insurance, homelessness) were also evaluated. The data set was disaggregated by birth cohort to include Silent Generation (SG) (1928-45), Baby Boomer (BB) (1946-64), Generation X (Gen X) (1965-80), Millennial (1981-96) and Generation Z (1997-2012). Descriptive statistics and chi-square analysis were performed. Overall, 83,817 patients were tested for HCV (50.6% of eligible); 6187 (7.4%) were HCV Ab positive, and 2665 were HCV RNA positive (3.2%). RNA-positive individuals were more likely to be white (70.4%) and male (67.7%); generational distribution was similar (BB 33.3%, Gen X 32.0% and Millennials 32.7%). Amongst Ab-positive patients, white (45.5%), male (47.2%) and Millennial (49.7%) individuals were most likely to be RNA-positive. Overall, 28.1% of the RNA-positive cohort successfully linked to care; linkage to care rates were significantly higher in older generations (38.1% in BB vs. 17.8% in Millennials) (p < .00001). Over 90% were identified as having at least one linkage to care barrier. Younger generations (Gen X and Millennials) were disproportionately impacted by linkage barriers, including incarceration, lack of health insurance, history of mental health and substance use disorders, as well as history of or active injection drug use (IDU) (p < .00001). Older generations (SG and BB) were more likely to be impacted by competing medical comorbidities (p < .00001). The ED population represents a particularly vulnerable, at-risk cohort with a high prevalence of HCV and linkage to care barriers. While past HCV-specific recommendations and interventions have focused on Baby Boomers, this data suggests that younger generations, including Gen X and Millennials, are increasingly affected by HCV and face disparate social risk and social need factors which impede definitive care linkage and treatment., (© 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Gold nanoparticles (AuNPs) exhibit improved optical and spectral properties compared to bulk materials, making them suitable for the detection of DNA, RNA, antigens, and antibodies. Here, we describe a simple, selective, and rapid non-cross linking detection assay, using approx. 35 nm spherical Au nanoprobes, for a common mutation occurring in exon 19 of the epidermal growth factor receptor (EGFR), associated with non-small-cell lung cancer cells. AuNPs were synthesized based on the seed-mediated growth method and functionalized with a specific 16 bp thiolated oligonucleotide using a pH-assisted method. Both AuNPs and Au nanoprobes proved to be highly stable and monodisperse through ultraviolet-visible spectrophotometry, dynamic light scattering (DLS), and electrophoretic light scattering (ELS). Our results indicate a detection limit of 1.5 µg mL -1 using a 0.15 nmol dm -3 Au nanoprobe concentration. In conclusion, this work presents an effective possibility for a straightforward, fast, and inexpensive alternative for the detection of DNA sequences related to lung cancer, leading to a potential platform for early diagnosis of lung cancer patients.

Background: Catheter implantation techniques for peritoneal dialysis (PD) have advanced significantly in recent years. We aimed to analyze the survival and associated complications of catheters inserted using a new technique that is guided by ultrasound and fluoroscopy and requires minimal tissue dissection. The procedure was performed by nephrologists in the outpatient basis, we compared these results of the minimally invasive insertion with traditional implantation using trocars., Methods: A total of 152 PD catheters were placed in 152 patients with stage 5 chronic kidney disease; 62.5% of the patients were men, with a mean age of 56.6 ± 18.5 years. The following two methods were used: minimally invasive insertion (MI group, n  = 73) and trocar insertion (T group, n  = 79). Patients in both the groups were followed prospectively for 26 months from the date of the first implantation., Results: Gender, age, and prevalence of diabetes mellitus were not significantly different between the groups, while the body mass index, presence of obesity, and abdominal scars from previous surgeries were higher in the MI group ( p  = 0.021). The incidence of catheter dysfunction was lower in the MI group compared to group T (6.8% vs 20.3%; p  = 0.019). Exit site infection was also lower with the new technique (4.1% vs . 18.9%; p  = 0.005). Further, the cumulative incidence of peritonitis also reduced with MI ( p  = 0.034). Finally, the overall catheter survival at 1 year was 89%, which has been shown as higher in group MI (95% vs 82% in group T; p  = 0.025)., Conclusion: The MI technique for catheter insertion showed low complication rates and excellent catheter survival as compared to traditional implantation methods; thus, it may be an alternative method for PD catheter placement., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The US government has established a national goal of hepatitis C virus (HCV) elimination by 2030. To date, most HCV elimination planning and activity have been at the state level. Fifteen states presently have publicly available HCV elimination plans. In 2019, Louisiana and Washington were the first states to initiate 5-year funded HCV elimination programs. These states differ on motivation for pursuing HCV elimination and ranking on several indicators. Simultaneously, however, they have emphasized several similar elimination components including HCV screening promotion through public awareness, screening expansion, surveillance enhancement (including electronic reporting and task force development), and harm reduction. The 13 other states with published elimination plans have proposed the majority of the elements identified by Louisiana and Washington, but several have notable gaps. Louisiana's and Washington's comprehensive plans, funding approaches, and programs provide a useful framework that can move states and the nation toward HCV elimination., Competing Interests: Financial Disclosures of Potential and Actual Conflicts of Interest: R.F. has received funds paid to his institution from Gilead Sciences, Inc, Abbvie, Merck & Co, Inc, and a consulting fee from Thera technologies. S.N.K. has received funds paid to his institution from Gilead Sciences, Inc, for research related to hepatitis C and COVID-19. G.L.T. is a member of the Speaker's Bureau for Gilead Sciences, Inc. A.H.T. has received honoraria and funds to his institution from Gilead Sciences. None of the other authors have any conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Introduction: The role of the Emergency Department (ED) as a vital constituent in Hepatitis C (HCV) screening has become increasingly evident. A key component of the ED's role in HCV screening is the ability to effectively link HCV-RNA positive patients to definitive, HCV-specific care, to include direct-acting antiviral (DAA) medication with resultant sustained virologic response (SVR). We sought to consider the rate of HCV-specific linkage, DAA initiation, and SVR obtained in HCV patients identified from an ED screening program., Methods: A retrospective chart review was conducted in February of 2022 of all individuals who participated in an opt-out ED-based HCV screening program between January 2018 and December 2019. Data was disaggregated by race, gender, age/birth cohort, insurance status, and achievement of sustained virologic response (SVR). Bivariate analysis using Pearson's chi-square was utilized to compare outcomes based on insurance status, race, sex, and birth cohort., Results: Of 66,634 individuals screened for HCV during the study period, 885 (1.33%) patients were RNA-positive. Of those individuals, 121 (13.67%) were linked to HCV-specific care. Of those linked, the majority (66.9%) were male, white (66.1%; 33.1% Black), baby boomers or older (53.7%) and publicly insured (57.9%; private insurance 23.1%, self-pay 19%). Among linked patients, 88 (72.7%) started DAA medication. Mirroring linked demographics, majority were male (64.8%), white (64.8%), baby boomers or older (52.3%), and publicly insured (57.6%). White patients initiated on DAA were more likely to obtain SVR (64.9% versus 41.9% Black; p = .04) and uninsured patients were more likely to obtain SVR (82.4% versus 50.7% insured; p = .02). Bivariate consideration of SVR-patients specifically demonstrates that Black patients tended to be older, with significant overrepresentation of Baby boomers (77.5%) as compared to whites (37.5%; p < .0001). Black patients were also more likely to be publicly insured (82.5%) while white patients were more likely to have private insurance (28.8%) or be uninsured (26.3%) than their Black counterparts (12.5% and 5% respectively; p < .05)., Conclusion: An ED-based HCV screening program can result in successful HCV-specific linkage and care, to include DAA initiation and ultimately, SVR. Among linked patients, specific cohort considerations may demonstrate differences in age and insurance status which may have implications on DAA application and adherence, and therefore, individual ability to achieve SVR., Competing Interests: Declaration of Competing Interest LAW reports no conflict of interest. LW reports no conflict of interest. MF reports no conflict of interest. TR reports no conflict of interest. DTH reports no conflict of interest. RF reports no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Early and accurate detection of infection by pathogenic microorganisms, such as Plasmodium, the causative agent of malaria, is critical for clinical diagnosis and ultimately determines the patient's outcome. We have combined a polystyrene-based microfluidic device with an immunoassay which utilises Surface-Enhanced Raman Spectroscopy (SERS) to detect malaria. The method can be easily translated to a point-of-care testing format and shows excellent sensitivity and specificity, when compared to the gold standard for laboratorial detection of Plasmodium infections. The device can be fabricated in less than 30 min by direct patterning on shrinkable polystyrene sheets of adaptable three-dimensional microfluidic chips. To validate the microfluidic system, samples of P. falciparum -infected red blood cell cultures were used. The SERS-based immunoassay enabled the detection of 0.0012 ± 0.0001% parasitaemia in a P. falciparum -infected red blood cell culture supernatant, an ∼7-fold higher sensitivity than that attained by most rapid diagnostic tests. Our approach successfully overcomes the main challenges of the current Plasmodium detection methods, including increased reproducibility, sensitivity, and specificity. Furthermore, our system can be easily adapted for detection of other pathogens and has excellent properties for early diagnosis of infectious diseases, a decisive step towards lowering their high burden on healthcare systems worldwide.

Importance: Direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection is highly effective but remains underused. Understanding disparities in the delivery of DAAs is important for HCV elimination planning and designing interventions to promote equitable treatment., Objective: To examine variations in the receipt of DAA in the 6 months following a new HCV diagnosis., Design, Setting, and Participants: This retrospective cohort study used national Medicaid claims from 2017 to 2019 from 50 states, Washington DC, and Puerto Rico. Individuals aged 18 to 64 years with a new diagnosis of HCV in 2018 were included. A new diagnosis was defined as a claim for an HCV RNA test followed by an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis code, after a 1-year lookback period., Main Outcomes and Measures: Outcome was receipt of a DAA prescription within 6 months of diagnosis. Logistic regression was used to examine demographic factors and ICD-10-identified comorbidities associated with treatment initiation., Results: Among 87 652 individuals, 43 078 (49%) were females, 12 355 (14%) were age 18 to 29 years, 35 181 (40%) age 30 to 49, 51 282 (46%) were non-Hispanic White, and 48 840 (49%) had an injection drug use diagnosis. Of these individuals, 17 927 (20%) received DAAs within 6 months of their first HCV diagnosis. In the regression analyses, male sex was associated with increased treatment initiation (OR, 1.24; 95% CI, 1.16-1.33). Being age 18 to 29 years (OR, 0.65; 95% CI, 0.50-0.85) and injection drug use (OR, 0.84; 95% CI, 0.75-0.94) were associated with decreased treatment initiation. After adjustment for state fixed effects, Asian race (OR, 0.50; 95% CI, 0.40-0.64), American Indian or Alaska Native race (OR, 0.68; 95% CI, 0.55-0.84), and Hispanic ethnicity (OR, 0.81; 95% CI, 0.71-0.93) were associated with decreased treatment initiation. Adjustment for state Medicaid policy did not attenuate the racial or ethnic disparities., Conclusions: In this retrospective cohort study, HCV treatment initiation was low among Medicaid beneficiaries and varied by demographic characteristics and comorbidities. Interventions are needed to increase HCV treatment uptake among Medicaid beneficiaries and to address disparities in treatment among key populations, including younger individuals, females, individuals from minoritized racial and ethnic groups, and people who inject drugs.

Objective: Hepatitis C virus (HCV) co-infection is associated with increased morbidity and mortality in people with HIV (PWH). Sustained virological response (SVR) decreases the risk of HCV-associated morbidity. We compared mortality, risk of AIDS-defining events, and non-AIDS nonliver (NANL) cancers between HCV-co-infected PWH who reached SVR and mono-infected PWH., Design: Adult PWH from 21 cohorts in Europe and North America that collected HCV treatment data were eligible if they were HCV-free at the time of ART initiation., Methods: Up to 10 mono-infected PWH were matched (on age, sex, date of ART start, HIV acquisition route, and being followed at the time of SVR) to each HCV-co-infected PWH who reached SVR. Cox models were used to estimate relative hazards (hazard ratio) of all-cause mortality, AIDS-defining events, and NANL cancers after adjustment., Results: Among 62 495 PWH, 2756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12-0.73] for mortality, 0.85 [0.42-1.74] for AIDS-defining events, and 1.21 [0.86-1.72] for NANL cancer., Conclusion: PWH who reached SVR a short time after HCV acquisition were not at higher risk of overall mortality compared with mono-infected PWH. However, the apparent higher risk of NANL cancers in HCV-co-infected PWH who reached SVR after a DAA-based treatment compared with mono-infected PWH, though compatible with a null association, suggests a need for monitoring of those events following SVR., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ongoing sexual transmission presents a significant barrier to viral hepatitis control. Endemic transmission of hepatitis A virus continues through communities of men with male sex partners, despite vaccine availability. Increased incidence of hepatitis B virus from 2014-2018 prompted expanded vaccination guidelines, but uptake and physician awareness remain poor. Hepatitis C virus while strongly associated with injection drug use, is also transmitted by high-risk sexual contact. Despite universal screening recommendations and curative treatment, incidence continues to increase. Even with safe and highly effective vaccinations or treatments, sexual transmission of viral hepatitides must be addressed to achieve disease elimination., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The development of rapid, reliable, and low-cost methods that enable discrimination among clinically relevant bacteria is crucial, with emphasis on those listed as WHO Global Priority 1 Critical Pathogens, such as carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant or ESBL-producing Klebsiella pneumoniae . To address this problem, we developed and validated a protocol of surface-enhanced Raman spectroscopy (SERS) with silver nanostars for the discrimination of A. baumannii and K. pneumoniae species, and their globally disseminated and clinically relevant antibiotic resistant clones. Isolates were characterized by mixing bacterial colonies with silver nanostars, followed by deposition on filter paper for SERS spectrum acquisition. Spectral data were processed with unsupervised and supervised multivariate data analysis methods, including principal component analysis (PCA) and partial least-squares discriminant analysis (PLSDA), respectively. Our proposed SERS procedure using silver nanostars adsorbed to the bacteria, followed by multivariate data analysis, enabled differentiation between and within species. This pilot study demonstrates the potential of SERS for the rapid discrimination of clinically relevant A. baumannii and K. pneumoniae species and clones, displaying several advantages such as the ease of silver nanostars synthesis and the possible use of a handheld spectrometer, which makes this approach ideal for point-of-care applications.

In Brazil, most hemodialysis (HD) patients are treated by the country's public health system. However, accessibility to healthcare is different for public and private patients. This study aimed to identify the profile of vascular access in a Brazilian HD sample. Additionally, it aimed to examine the influence of public and private health insurance, accessibility to endovascular treatments, and timely arteriovenous access creation on the prevalence of tunneled catheters (TCs), non-tunneled catheters (NTCs), and arteriovenous (AV) access. We conducted a cross-sectional electronic survey across 834 centers. Centers were inquired about the number of patients with public and private health insurance, the profiles of vascular access, time for AV access creation, accessibility to TC insertion and endovascular treatments, and the availability of peritoneal dialysis and kidney transplantation. Logistic regression and multilevel logistic regression were performed to evaluate possible interactions between the independent variables. A total of 7,973 patients across 47 HD centers were included in the survey. Public health patients accounted for 77% of the study sample. The overall vascular access profiles of the public and private insurance groups were significantly different ( p  < 0.001). For patients with public health insurance, the prevalence of any catheter was 25%, while that for private patients was 31.8% ( p  < 0.001). The prevalence of TCs was more common in private patients (15.3% vs. 23.1%, p  < 0.001). AV accesses were more common in public health patients (75% vs. 68.2%, p  < 0.001), as were fistulas (72.4% vs. 63.1%, p  < 0.001). AV grafts were more prevalent among patients with private insurance (2.6 vs. 5.1%, p  < 0.001). The availability of endovascular treatments increased the chance of having a TC by 2.3-fold (OR = 2.33, 95% CI = 1.30-4.18); however, it did not reduce the chance of having any catheter. A high chance of having a catheter was found when the time to AV access creation exceeded 60 days. The differences between public and private patients may be explained by underpayments and the decreased accessibility to care infrastructure in the public system, especially for endovascular treatments. In this sample, public health patients had a decreased risk of having a TC over an NTC. Differences in care accessibility and insurance type might influence the type of vascular access., Competing Interests: RP received speaker honoraria from Baxter Healthcare and BD. TM is employed by the Pontifícia Universidade Católica do Paraná and is a recipient of scholarships from the Brazilian Council for Research CNPq, received consulting fees from AstraZeneca and Baxter Healthcare and speaker honoraria from Astra Zeneca, Lilly-Boehringer, Baxter, and Takeda. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Franco, Chula, de Moraes and Campos.)

Hepatitis C virus (HCV) surveillance is a critical component of a comprehensive strategy to prevent and control HCV infection and HCV-related chronic liver disease. The emergency department (ED) has been increasingly recognized as a vital partner in HCV testing and linkage. We sought to consider active RNA HCV viremia over time in patients participating in an ED-based testing programme as a measure of local HCV surveillance and as a barometer of ED-testing programme impact. We performed a retrospective analysis of individuals participating in our ED-based HCV testing programme between 2015 and 2021. Chi-square tests were used to compare the demographic characteristics of HCV antibody positive tests with active viremia to those without active viremia. Cox proportional hazard models were used to estimate the trend in active viremia risk over time in the overall study population as well as in key subpopulations of interest. Of 5456 HCV antibody positive individuals, 3102 (56.8%) had active viremia. In the overall study population, we found that the risk of active viremia decreased by 4.8% per year during the study period (RR: 0.95, 95% CI: 0.93-0.97|p < .0001). Baby boomers experienced a 9% decrease in active viremia risk per year over the study period while non-baby boomers only had a 2% decrease in risk per year (p = .0009). Compared with insured patients, uninsured patients had a smaller decrease in risk of active HCV viremia per year (p = .003). No significant differences in the risk of active viremia over time were observed for gender (p = .4694) or by primary care provider status (p = .2208). In conclusion, this ED-based testing and linkage programme demonstrates significantly decreased active HCV viremia over time. It also highlights subpopulations, specifically non-baby boomers and uninsured patients, who may benefit from focused interventions to improve access to and adoption of definitive HCV care., (© 2022 John Wiley & Sons Ltd.)

Objectives: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection., Design: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing., Methods: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV., Results: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant., Conclusions: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART., (© 2021 British HIV Association.)

Introduction: Arteriovenous fistulas (AVF) are the first choice vascular access for hemodialysis. However, they present a high incidence of venous stenosis leading to thrombosis. Although training in interventional nephrology may improve accessibility for treatment of venous stenosis, there is limited data on the safety and efficacy of this approach performed by trained nephrologists in low-income and developing countries., Methods: This study presents the retrospective results of AVF angioplasties performed by trained nephrologists in a Brazilian outpatient interventional nephrology center. The primary outcome was technical success rate (completion of the procedure with angioplasty of all stenoses) and secondary outcomes were complication rates and overall AVF patency., Findings: Two hundred fifty-six angioplasties were performed in 160 AVF. The technical success rate was 88.77% and the main cause of technical failure was venous occlusion (10%). The incidence of complications was 13.67%, with only one patient needing hospitalization and four accesses lost due to the presence of hematomas and/or thrombosis. Grade 1 hematomas were the most frequent complication (8.2%). The overall patency found was 88.2 and 80.9% at 180 and 360 days after the procedure, respectively., Conclusion: Our findings suggest that AVF angioplasty performed by trained nephrologists has acceptable success rates and patency, with a low incidence of major complications as well as a low need for hospitalization.

Background: End-stage liver disease (ESLD) is a leading cause of non-AIDS-related death among people with HIV (PWH). Factors that increase the progression of liver disease include comorbidities and HIV-specific factors, but we currently lack a tool to apply this evidence into clinical practice., Methods: We developed and validated a risk prediction model for ESLD among PWH who received care in 12 cohorts of the North American AIDS Cohort Collaboration on Research and Design between 2000 and 2016 and had fibrosis-4 index > 1.45. The first occurrence of ascites, variceal bleed, spontaneous bacterial peritonitis, or hepatic encephalopathy was verified by standardized medical record review. The Bayesian model averaging was used to select predictors among biomarkers and diagnoses and the Harrell C statistic to assess model discrimination., Results: Among 13,787 PWH in the training set, 82% were men and 54% were Black with a mean age of 48 years. Three hundred ninety ESLD events occurred over a mean 5.4 years. Among the ESLD cases, 52% had hepatitis C virus, 15% hepatitis B virus, and 31% alcohol use disorder. Twelve factors together predicted ESLD risk moderately well (C statistic 0.79, 95% confidence interval: 0.76 to 0.81): age, sex, race/ethnicity, chronic hepatitis B or C, and routinely collected laboratory values reflecting hepatic impairment (serum albumin, aspartate aminotransferase, total bilirubin, and platelets) and lipid metabolism (triglycerides, high-density lipoprotein, and total cholesterol). Our model performed well in the test set (C statistic 0.81, 95% confidence interval: 0.76 to 0.86)., Conclusion: This model of readily accessible clinical parameters predicted ESLD in a large diverse population of PWH., Competing Interests: E.R.C. has received research grants paid to UC Reagents from Gilead Sciences and Merck & Co., Inc., and has been on an advisory board for Gilead Sciences. M.K. reports grants for investigator-initiated studies from ViiV Healthcare, AbbVie, Merck, and Gilead Sciences and consulting fees from ViiV Healthcare, Merck, AbbVie, and Gilead Sciences. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women., (Copyright © 2021 Elsevier Inc. All rights reserved.)

A new avenue has opened up for applications of surface-enhanced Raman spectroscopy (SERS) in the biomedical field, mainly due to the striking advantages offered by SERS tags. SERS tags provide indirect identification of analytes with rich and highly specific spectral fingerprint information, high sensitivity, and outstanding multiplexing potential, making them very useful in in vitro and in vivo assays. The recent and innovative advances in nanomaterial science, novel Raman reporters, and emerging bioconjugation protocols have helped develop ultra-bright SERS tags as powerful tools for multiplex SERS-based detection and diagnosis applications. Nevertheless, to translate SERS platforms to real-world problems, some challenges, especially for clinical applications, must be addressed. This review presents the current understanding of the factors influencing the quality of SERS tags and the strategies commonly employed to improve not only spectral quality but the specificity and reproducibility of the interaction of the analyte with the target ligand. It further explores some of the most common approaches which have emerged for coupling SERS with microfluidic technologies, for biomedical applications. The importance of understanding microfluidic production and characterisation to yield excellent device quality while ensuring high throughput production are emphasised and explored, after which, the challenges and approaches developed to fulfil the potential that SERS-based microfluidics have to offer are described., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Cutaneous leishmaniasis (CL) is a parasitic disease that produces chronic skin ulcers. Although it has a worldwide presence, it is a neglected disease that still requires novel tools for its management. In order to study the use of optical tools in CL, this article presents a preliminary study of the correlation between CL histopathological and optical parameters. Optical parameters correspond to absorption and scattering coefficients obtained from diffuse reflectance spectra of treated CL in golden hamsters. Independently, histopathological data were collected from the same hamsters. As a result, after Spearman correlation and the Kruskal-Wallis test, inverse correlation was found between absorption/scattering optical parameters and inflammatory histopathological values, such as the scattering parameter related to the diameter of fibroblasts with the histopathological parameters of fibrosis, polymorphonuclear neutrophils, lymphocytes, plasmocytes, hyperplasia, and Leishmania , and the absorption parameter oxygen saturation showed a relation with the granulation tissue histopathological parameter. These correlations agree with the expected behavior of tissue composition during the healing process in CL. The results correspond to a proof of concept that shows that optical diffuse reflectance-based tools and methods could be considered as an alternative to assist in CL diagnosis and treatment follow-up.

Objective: To analyze the effects of neuromuscular electrical stimulation of the femoral quadriceps associated or not with whey protein supplementation on the electromyographic activity and body mass distribution in volunteers undergoing anterior cruciate ligament reconstruction., Methods: 24 volunteers were randomly divided into three groups: basal control, whey protein in association with neuromuscular electrical stimulation, and neuromuscular electrical stimulation alone., Results: In the postoperative evaluation, during the mini squat, the basal group showed a decrease in the electromyographic activity of the vastus medialis (p = 0.005, eyes open; p = 0.003, eyes closed), vastus lateralis (p = 0.005, eyes open; p = 0.020; eyes closed) and rectus femoris (p = 0.075, eyes open; p = 0.074, eyes closed) and of body mass distribution in the injured limb (p < 0.001, eyes open; p < 0.001, eyes closed), and in the healthy limb (p < 0.001, eyes open; p < 0.001, eyes closed)., Conclusion: The early use of neuromuscular electrical stimulation of the quadriceps femoris maintained the electromyographic activity of the vastus medialis and vastus lateralis muscles and prevented asymmetries in body mass distribution 15 days after anterior cruciate ligament reconstruction. Level of Evidence I, High quality randomized trial. , Competing Interests: All authors declare no potential conflict of interest related to this article.

The development of robust and sensitive point-of-care testing platforms is necessary to improve patient care and outcomes. Surface-enhanced Raman scattering (SERS)-based immunosensors are especially suited for this purpose. Here, we present a highly sensitive and selective SERS immunoassay, demonstrating for example the detection of horseradish peroxidase (HRP), in a sandwich format. The strength of our biosensor lies in merging: (i) SERS-immunotags based on gold nanostars, allowing exceptional intense SERS from attached Raman probes, covalent attachment of anti-HRP antibodies by a simple chemical method providing exceptional antigen binding activity; (ii) the ease of preparation of the capture platform from a regenerated cellulose-based hydrogel, a transparent material, ideal for microfluidics applications, with low background fluorescence and Raman signal, particularly suited for preserving high activity of the covalently bound anti-HRP antibodies. The sandwich complexes formed were characterised by atomic force microscopy, and by scanning electron microscopy coupled with electron diffraction spectroscopy; and (iii) the robustness of the simple Classical Least Squares method for SERS data analysis, resulting in superior discrimination of SERS signals from the background and much better data fitting, compared to the commonly used peak integral method. Our SERS immunoassay greatly improves the detection limits of traditional enzyme-linked immunosorbent assay approaches, and its performance is better or comparable to those of existing SERS-based immunosensors. Our approach successfully overcomes the main challenges of application at point-of-care, including increasing reproducibility, sensitivity, and specificity, associated with an environmentally friendly and robust design. Also, the proposed design withstands several cycles of regeneration, a feature absent in paper-SERS immunoassays and this opens the way for sensitive multiplexing applications on a microfluidic platform.

Objective: Despite the Centers for Disease Control and Prevention (CDC) and U.S. Preventive Services Task Force (USPSTF) recommending universal hepatitis C virus (HCV) screening in pregnancy Society for Maternal-Fetal Medicine (SMFM) and American College of Obstetricians and Gynecologists (ACOG) continue to endorse risk-based screening for HCV in pregnancy. We hypothesized that universal screening is associated with increased HCV diagnosis and postpartum linkage to HCV care compared with risk-based screening., Study Design: This retrospective cohort study included pregnant women screened for HCV at a single tertiary-care center. We defined two cohorts: women managed with risk-based (January 2014-October 2016) or universal HCV screening (November 2016-December 2018). Screening was performed with ELISA antibody testing and viremia confirmed with HCV ribonucleic acid (RNA) polymerase chain reaction (PCR). Primary outcomes were the rate of HCV screen positivity and postpartum linkage to care., Results: From 2014 to 2018, 16,489 women delivered at our institution, of whom 166 screened positive for HCV. A total of 7,039 pregnant women were screened for HCV: 266 with risk-based and 6,773 with universal screening; 29% (76/266) were positive HCV antibody screening (HCVAb + ) in the risk-based cohort and 1.3% (90/6,773) in the universal cohort. HCVAb+ women in the risk-based cohort were more likely to have a positive drug screen. Only 69% (62/90) of HCVAb+ women in the universal cohort met the criteria for risk-based testing. Of the remaining 28 women, 6 (21%) had active viremia (HCV RNA + ). Of the 166 HCVAb+ women, 64% (103/166) were HCV RNA + -51 of 266 (19%) in the risk-based and 52 of 6,773 (0.8%) in the universal cohort. Of HCVAb+ women, 75% (125/166) were referred postpartum for HCV evaluation and 27% (34/125) were linked to care. Only 9% (10/103) of women with viremia initiated treatment within 1 year of delivery., Conclusion: Universal HCV screening in pregnancy identified an additional 31% of HCVAb+ women compared with risk-based screening. Given low rates of HCV follow-up and treatment regardless of screening modality, further studies are needed to address barriers to postpartum linkage to care., Key Points: · Ideal screening for HCV in pregnancy is unknown.. · We explore screening strategies in pregnancy to linkage to HCV care.. · Regardless of screening strategy there is low rates of postpartum linkage to HCV care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Eradication of hepatitis C virus (HCV) in HIV disease decreases liver and non-liver-related morbidity and mortality. Elevated markers of monocyte/macrophage activation (soluble CD163 and sCD14) are associated with excess non-AIDS morbidity and mortality in HIV. We examined the effect of HCV eradication on these markers in relation to change in hepatic fibrosis., Design: A nested substudy within a longitudinal observational cohort., Methods: We studied 126 HIV/HCV-coinfected women successfully treated for HCV, with undetectable HCV RNA at least 12 weeks after therapy completion. sCD163 and sCD14 were measured in serum collected before and after HCV eradication. Results were correlated with changes in markers of hepatic fibrosis., Results: Mean age of participants was 56.3 years, mean CD4+ cell count was 615, and 72% had suppressed HIV RNA. After treatment, sCD163 and sCD14 levels significantly decreased from pre-treatment levels in unadjusted analyses. After adjusting for age, race, hepatic fibrosis status, baseline HCV RNA, CD4 count and HIV RNA status, cigarette smoking, and alcohol use, the decreases in sCD163 and sCD14 remained significant. Decrease in pre-treatment to post-treatment sCD163 were significantly positively correlated with changes in FIB-4 (r = 0.250, P = 0.005) and APRI (r = 0.262, P = 0.003); similarly decrease in sCD14 was significantly positively correlated with changes in FIB-4 (r = 0.333, P = 0.0001) and APRI (r = 0.457, P < 0.0001)., Conclusion: HCV eradication is associated with significant reductions in monocyte/macrophage activation markers that correlate with reductions in markers of hepatic fibrosis. These findings support broad access to and early initiation of HCV treatment in order to decrease immune activation and improve health in HIV-infected persons., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic hepatitis C virus (HCV) infection continues to be transmitted to hemodialysis (HD) patients within HD facilities globally. The goal of the World Health Organization to micro-eliminate HCV infection from the HD population by the year 2030 is not on target to be achieved. Obstacles to eliminate HCV in HD settings remain daunting due to a complex system created by a confluence of guidelines, legislation, regulation, and economics. HCV prevalence remains high and seroconversion continues among the HD patient population globally as a result of the HD procedure. Preventive strategies that effectively prevent HCV transmission, treatment-as-prevention, and rapid referral to treatment balanced with kidney transplant candidacy should be added to the current universal precautions approach. A safer system must be designed before HCV transmission can be halted and eliminated from the HD population., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

The Fistula First Breakthrough Initiative, founded in 2003, was responsible for changing the access profile in the United States, increasing the prevalence of arteriovenous fistulas (AVFs) by 50% and reducing that of arteriovenous grafts (AVGs). However, the concept that AVFs are always the best access for all patients has been challenged. Discussion points are: (1) the questionable survival benefit of AVFs over AVGs, if one takes into account the high rates of primary AVF failure; (2) the potential benefits of using AVGs for greater primary success; and (3) the questionable benefit of AVFs over AVGs in patients with shorter survival, such as the elderly. The high rate of primary failure and maturation procedures leads to prolonged use of catheters, and it is one of the weaknesses of the fistula first strategy. AVGs proved to be better than AVFs as a second access after the failure of a first AVF, and in patients with non-ideal vessels, with greater primary success and reduced catheter times. AVGs appear to have a similar survival to AVFs in patients older than 80 years, with less primary failures and interventions to promote maturation. The most recent KDOQUI guidelines suggest an individualized approach in access planning, taking into account life expectancy, comorbidities and individual vascular characteristics, with the aim of chosing adequate access for the right patient, at the right time, for the right reasons.

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable "light-to-heat" conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model.

Background: Direct-acting antiviral (DAA) therapy among hepatitis C virus (HCV)-infected kidney transplant recipients is associated with short-term improvement in protein/creatinine (P/C) ratios, but how HCV cure affects long-term graft outcomes remains unknown., Methods: This is a retrospective follow-up study of 59 HCV-infected patients who underwent kidney transplant at the University of Alabama at Birmingham between 2007-2015 who were followed until the end of 2017. We examined the association of DAA-induced HCV cure with graft failure or death by survival analyses (Kaplan-Meier, Cox regression)., Results: Mean age was 55 years, 73% were African American, and 68% were male. Median baseline creatinine was 1.4 mg/dL, P/C ratio was 0.5, and estimated glomerular filtration rate (eGFR) was 59 mL/min. Of those who received DAA, 24 (83%) achieved cure. The remaining 5 DAA patients (17%) did not have documented evidence of sustained virologic response (SVR). Overall, 19 (32%) patients experienced graft failure or death; with lower incidence in treated patients than untreated (4 vs 15 events; 2.6 vs 10.3 per 100 person-years [cHR 0.19, 95% CI: 0.06-0.66]). When adjusted for age, sex, race, and proteinuria, the association remained strong and invariant across time-varying (aHR 0.30, 95% CI: 0.08-1.10), time-averaged (aHR 0.28, 95% CI: 0.07-1.07), and time-varying-cumulative (aHR 0.32, 95% CI: 0.08-1.21) proteinuria metrics., Conclusions: DAAs therapy was associated with improved graft survival and reduced mortality. While not statistically significant, the association was strong, and these single-center findings warrant larger studies to demonstrate the benefits of HCV treatment in this population., Competing Interests: The authors do not have any conflicts of interest to report., (© Pathogens and Immunity 2020.)

Background: The effectiveness of hepatitis C testing and linkage-to-care (LTC) is poorly characterized in low-resource jurisdictions facing gaps in harm reduction, including illegality of syringe exchange services. Effectiveness of a community-based test/LTC program was evaluated in Alabama., Methods: In 2016-2018, shelters, drug treatment centers (DTCs), AIDS organizations, and Federally Qualified Health Centers (FQHCs) engaged in screening/LTC. A coordinator navigated individuals to confirm viremia and link to substance use treatment or primary care with hepatitis C prescribers., Results: Point-of-care (POC) tested 4293 individuals (10% [427] antibody-positive, 71% [299/419] RNA performed, 80% [241/299] viremia confirmed) and 93% linked to care (225/241). Electronic medical record (EMR)-based reflex strategy screened 4654 (15% [679] antibody positive, 99% [670/679] RNA performed, 64% [433/679] viremia confirmed) and 85% linked to care (368/433). We observed higher odds of RNA confirmation in EMR-based reflex versus POC (OR, 2.07; P < .0001) and higher odds of LTC in EMR-based reflex versus POC (OR, 1.51; P < .0001). Overall, 53% individuals tested were nonbaby boomers., Conclusions: In Alabama, screening at high-risk settings identified significant hepatitis C burden and reflex testing outperformed point-of-care linkage indicators. Colocating testing in DTCs and treatment in FQHCs provided key LTC venues to at-risk younger groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Considering the new coronavirus epidemic (Covid-19), the Brazilian Society of Nephrology, represented by the Peritoneal Steering Committee, in agreement with the and the Dialysis Department, developed a series of recommendations for good clinical practices for peritoneal dialysis (PD) clinics, to be considered during the period of the Covid-19 epidemic. We aim to minimize the disease spread, protecting patients and staff, and ensuring the quality of the treatment provided and adequate follow-up for PD patients. The recommendations suggested at this moment must be adapted to each clinic's reality and the conditions of the structural and human resources, dependent on the adequate financial provision of the public health system for its full implementation.

Vascular accesses for hemodialysis are considered the patient's lifeline and their maintenance is essential for treatment continuity. Following the example of institutions in other countries affected by the Covid-19 pandemic, the Brazilian Society of Nephrology developed these guidelines for healthcare services, elaborating on the importance of carrying out procedures for the preparation and preservation of vascular accesses. Creating definitive accesses for hemodialysis, grafts and arteriovenous fistulas are non-elective procedures, as well as the transition from the use of non-tunneled catheters to tunneled catheters, which cause less morbidity. In the case of patients with suspected or confirmed coronavirus infection, one may postpone the procedures for the quarantine period, to avoid spreading the disease.

Objective: We implemented a nontargeted, opt-out HCV testing and linkage to care (LTC) program in an academic tertiary care emergency department (ED). Despite research showing the critical role of ED-based HCV testing programs, predictors of LTC have not been defined for patients identified through the nontargeted ED testing strategy. In order to optimize health outcomes for patients with HCV, we sought to identify predictors of LTC failure., Methods: This was a retrospective cohort study of adult patients who were tested for HCV in the ED between August 2015 and September 2018 and were confirmed to have chronic HCV infection through RNA testing. We used logistic regression to assess the relationship between candidate predictors and the primary outcome, LTC failure, which was defined as a patient not being seen by an HCV treating provider after discharge from the ED., Results: Of 53,297 patients tested, 1,674 (3.1%) had HCV on confirmatory testing, and 355 (21%) linked to care. Predictors of LTC failure included younger age (OR 0.96, 95% CI 0.95-0.97), white race (OR 1.65, 95% CI 1.23-2.22), homelessness (OR 1.91, 95% CI 1.19-3.08), substance use (OR 1.77, 95% CI 1.34-2.34), and comorbid psychiatric illness (OR 2.16, 95% CI 1.59-2.94). Patients with significant medical comorbidities (OR 0.57, 95% CI 0.41-0.78) or HIV co-infection (OR 0.11, 95% CI 0.03-0.46) were less likely to experience LTC failure., Conclusions: One in five HCV-infected patients identified by ED-based nontargeted testing successfully linked to an HCV treating provider. Predictors of LTC failure may guide the development of targeted interventions to improve LTC success., Competing Interests: Declaration of Competing Interest JAB reports funding from the National Center for the Advancement of Translational Science at the National Institutes of Health (TL1TR001418). JBR reports research funding from Gilead Sciences. RAF reports research funding from Gilead Sciences, Merck & Co., and Janssen Pharmaceutica, and has received consulting fees from AbbVie. SSC reports no conflicts of interest. LAW reports no conflicts of interest. JWG reports research funding from Gilead Sciences. EPH reports research funding from Gilead Sciences., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Identifying persons with hepatitis C virus (HCV) infection has become an urgent public health challenge because of increasing HCV-related morbidity and mortality, low rates of awareness among infected persons, and the advent of curative therapies (1). Since 2012, CDC has recommended testing of all persons born during 1945-1965 (baby boomers) for identification of chronic HCV infection (1); urban emergency departments (EDs) are well positioned venues for detecting HCV infection among these persons. The United States has witnessed an unprecedented opioid overdose epidemic since 2013 that derives primarily from commonly injected illicit opioids (e.g., heroin and fentanyl) (2). This injection drug use behavior has led to an increase in HCV infections among persons who inject drugs and heightened concern about increases in human immunodeficiency virus (HIV) and HCV infection within communities disproportionately affected by the opioid crisis (3,4). However, targeted strategies for identifying HCV infection among persons who inject drugs is challenging (5,6). During 2015-2016, EDs at the University of Alabama at Birmingham; Highland Hospital, Oakland, California; Johns Hopkins Hospital, Baltimore, Maryland; and Boston University Medical Center, Massachusetts, adopted opt-out (i.e., patients can implicitly accept or explicitly decline testing), universal hepatitis C screening for all adult patients. ED staff members offered HCV antibody (anti-HCV) screening to patients who were unaware of their status.* During similar observation periods at each site, ED staff members tested 14,252 patients and identified an overall 9.2% prevalence of positive results for anti-HCV among the adult patient population. Among the 1945-1965 birth cohort, prevalence of positive results for anti-HCV (13.9%) was significantly higher among non-Hispanic blacks (blacks) (16.0%) than among non-Hispanic whites (whites) (12.2%) (p<0.001). Among persons born after 1965, overall prevalence of positive results for anti-HCV was 6.7% and was significantly higher among whites (15.3%) than among blacks (3.2%) (p<0.001). These findings highlight age-associated differences in racial/ethnic prevalences and the potential for ED venues and opt-out, universal testing strategies to improve HCV infection awareness and surveillance for hard-to-reach populations. This opt-out, universal testing approach is supported by new recommendations for hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of positive results for HCV infection is <0.1% (7)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Ricardo Franco reports grants and personal fees from Gilead during the conduct of the study, and personal fees from Abbvie and grants from Merck outside the submitted work. James Galbraith reports grants from Gilead Sciences outside the submitted work. Yu-Hsiang Hsieh reports grants from Gilead Sciences HIV FOCUS program during the conduct of the study. Elissa Schechter-Perkins reports grants from Gilead Sciences during the conduct of the study. Joel Rodgers reports grants from Gilead Sciences during the conduct of the study. Richard Rothman reports grants from Gilead FOCUS during the conduct of the study. Douglas White reports grants from Gilead Sciences during the conduct of the study. No other potential conflicts of interest were disclosed.

Background: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil., Material and Methods: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients' medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12., Results: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall ( P  = 0.03) and in cervical mucosa ( P  = 0.01). HIV+ women had significantly more abnormal cytological findings ( P  = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV ( P  = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa., Conclusion: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Pneumocystis jirovecii pneumonia (PcP) is a major human immunodeficiency virus (HIV)-related illness, rising among immunocompromised non-HIV patients and in developing countries. Presently, the diagnosis requires respiratory specimens obtained through invasive and costly techniques that are difficult to perform in all patients or implement in all economic settings. Therefore, the development of a faster, cost-effective, non-invasive and field-friendly test to diagnose PcP would be a significant advance. In this study, recombinant synthetic antigens (RSA) of P. jirovecii 's major surface glycoprotein (Msg) and kexin-like serine protease (Kex1) were produced and purified. These RSA were applied as antigenic tools in immunoenzymatic assays for detection of specific anti- P. jirovecii antibodies (IgG and IgM) in sera of patients with ( n = 48) and without ( n = 28) PcP. Results showed that only IgM anti- P. jirovecii levels were significantly increased in patients with PcP compared with patients without P. jirovecii infection ( p ≤ 0.001 with both RSA). Thus, two strip lateral flow immunoassays (LFIA), based on the detection of specific IgM anti- P. jirovecii antibodies in human sera samples, were developed using the innovative association of P. jirovecii' s RSA with spherical gold nanoparticles (AuNPs). For that, alkanethiol-functionalized spherical AuNPs with ca. ~40 nm in diameter were synthetized and conjugated with the two RSA (Msg or Kex1) produced. These AuNP-RSA conjugates were characterized by agarose gel electrophoresis (AGE) and optimized to improve their ability to interact specifically with serum IgM anti- P. jirovecii antibodies. Finally, two LFIA prototypes were developed and tested with pools of sera from patients with (positive sample) and without (negative sample) PcP. Both LFIA had the expected performance, namely, the presence of a test and control red colored lines with the positive sample, and only a control red colored line with the negative sample. These results provide valuable insights into the possibility of PcP serodiagnosis at point-of-care. The optimization, validation and implementation of this strip-based approach may help to reduce the high cost of medical diagnosis and subsequent treatment of PcP both in industrialized and low-income regions, helping to manage the disease all around the world., (Copyright © 2019 Tomás, de Almeida, Cardoso, Pinto, Pereira, Franco and Matos.)

Immunoassays using Surface-Enhanced Raman Spectroscopy are especially interesting on account not only of their increased sensitivity, but also due to its easy translation to point-of-care formats. The bases for these assays are bioconjugates of polyclonal antibodies and anisotropic gold nanoparticles functionalized with a Raman reporter. These bioconjugates, once loaded with the antigen analyte, can react on a sandwich format with the same antibodies immobilized on a surface. This surface can then be used for detection, on a microfluidics or immunochromatographic platform. Here, we have assembled bioconjugates of gold nanostars functionalized with 4-mercaptobenzoic acid, and anti-horseradish peroxidase antibodies. The assembly was by simple incubation, and agarose gel electrophoresis determined a high gold nanostar to antibody binding constant. The functionality of the bioconjugates is easy to determine since the respective antigen presents peroxidase enzymatic activity. Furthermore, the chosen antibody is a generic immunoglobulin G (IgG) antibody, opening the application of these principles to other antibody-antigen systems. Surface-Enhanced Raman Spectroscopy analysis of these bioconjugates indicated antigen detection down to 50 µU of peroxidase activity. All steps of conjugation were fully characterized by ultraviolet-visible spectroscopy, dynamic light scattering, ζ -Potential, scanning electron microscopy, and agarose gel electrophoresis. Based on the latter technique, a proof-of-concept was established for the proposed immunoassay.

Cutaneous leishmaniasis (CL) is a neglected tropical disease that requires novel tools for its understanding, diagnosis, and treatment follow-up. In the cases of other cutaneous pathologies, such as cancer or cutaneous ulcers due to diabetes, optical diffuse reflectance-based tools and methods are widely used for the investigation of those illnesses. These types of tools and methods offer the possibility to develop portable diagnosis and treatment follow-up systems. In this article, we propose the use of a three-layer diffuse reflectance model for the study of the formation of cutaneous ulcers caused by CL. The proposed model together with an inverse-modeling procedure were used in the evaluation of diffuse-reflectance spectral signatures acquired from cutaneous ulcers formed in the dorsal area of 21 golden hamsters inoculated with Leishmanisis braziliensis. As result, the quantification of the model's variables related to the main biological parameters of skin were obtained, such as: diameter and volumetric fraction of keratinocytes, collagen; volumetric fraction of hemoglobin, and oxygen saturation. Those parameters show statistically significant differences among the different stages of the CL ulcer formation. We found that these differences are coherent with histopathological manifestations reported in the literature for the main phases of CL formation.

Objectives: This study surveys medical education literature published over the last 25 years (1993-2018) to identify the factors scholars consider deleterious to outpatient teaching for medical students., Methods: This study conducts a review of medical education literature published between 1993 and 2018 using Medline, Lilacs, Ibecs, Cochrane Library, and Scielo databases. The following search terms were utilized: "Education, Medical, Undergraduate" AND "Ambulatory Care" AND "Teaching/methods" OR "Clinical Clerkship" OR "Preceptorship." This study focuses on papers describing deleterious factors for outpatient teaching with medical students and analyzes their results, discussions, and conclusions sections., Results: Of the 363 articles obtained, this study selected 33 for analysis. These papers identify numerous factors as barriers to outpatient education. For didactic purposes, these factors are categorized into four barrier groups: environment-institution, academic staff, students, and patients. Academic staff-related teaching barrier was the most frequently mentioned obstacle. Intense care schedule with little teaching time was considered the most common and relevant barrier to outpatient medical education, followed by inappropriate teaching environment and inadequate supervision model., Conclusions: There is a lack of recent literature on studies focusing on barriers to effective outpatient medical education. Factors identified as harmful to outpatient education have been pointed out by course directors, academic staff, and students in the literature. However, many of these factors remain overlooked by educators, who can use these factors to modify their academic activities for more effective results.

Surface-enhanced Raman Spectrosocopy (SERS) is a highly sensitive form of Raman spectroscopy, with strong selectivity for Raman-active molecules adsorbed to plasmonic nanostructured surfaces. Extremely intense Raman signals derive from "hotspots", generally created by the aggregation of a silver nanospheres colloid. An alternative and cleaner approach is the use of anisotropic silver nanoparticles, with intrinsic "hotspots", allowing a more controlled enhancement effect as it is not dependent on disordered nanoparticle aggregation. Here, a simple SERS-based test is proposed for Portuguese white wines fingerprinting. The test is done by mixing microliter volumes of a silver nanostars colloid and the white wine sample. SERS spectra obtained directly from these mixtures, with no further treatments, are analyzed by principal component analysis (PCA), using a dedicated software. Depending on the duration of the incubation period, different discrimination can be obtained for the fingerprinting. A "mix-and-read" approach, with practically no incubation, allows for a simple discrimination between the three white wines tested. An overnight incubation allows for full discrimination between varieties of wine ( Verde or Maduro ), as well as between wines from different Maduro wine regions. This use of SERS in a straightforward, fast and inexpensive test for wine fingerprinting, avoiding the need for prior sample treatment, paves the way for the development of a simple and inexpensive authenticity assay for wines from specific appellations.

Background: Direct-acting antiviral (DAA) therapy have been shown to be highly successful in clinical trials and observational studies, but less is known about treatment success in patients with a high burden of comorbid conditions, including mental health and substance use disorders. We evaluated DAA effectiveness across a broad spectrum of patients with human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection in routine clinical care, including those with psychosocial comorbid conditions., Methods: The primary end point was sustained virologic response (SVR), defined as HCV RNA not detected or <25 IU/mL ≥10 weeks after treatment. We calculated SVR rates and 95% confidence intervals (CIs) in a modified intent-to-treat analysis. We repeated this analysis after multiply imputing missing SVR values., Results: Among 642 DAA-treated patients, 536 had SVR assessments. The median age was 55 years; 79% were men, 59% black, and 32% white. Cirrhosis (fibrosis-4 index>3.25) was present in 24%, and 17% were interferon treatment experienced; 96% had genotype 1 infection and 432 (81%) had received ledipasvir-sofosbuvir. SVR occurred in 96.5% (95% CI, 94.5%-97.9%). Patients who were black, treatment experienced, or cirrhotic all had SVR rates >95%. Patients with depression and/or anxiety, psychotic disorder, illicit drug use, or alcohol use disorder also had high SVR rates, ranging from 95.4% to 96.8%. The only factor associated with lower SVR rate was early discontinuation (77.8%; 95% CI, 52.4%-93.6%). Similar results were seen in multiply imputed data sets., Conclusions: Our study represents a large multicenter examination of DAA therapy in HIV/HCV-coinfected patients. The broad treatment success we observed across this diverse group of patients with significant comorbid conditions is highly affirming and argues for widespread implementation of DAA therapy.

Progress in the field of biocompatible SERS nanoparticles has promising prospects for biomedical applications. In this work, we have developed a biocompatible Raman probe by combining anisotropic silver nanoparticles with the dye rhodamine 6G followed by subsequent coating with bovine serum albumin. This nanosystem presents strong SERS capabilities in the near infrared (NIR) with a very high (2.7 × 10⁷) analytical enhancement factor. Theoretical calculations reveal the effects of the electromagnetic and chemical mechanisms in the observed SERS effect for this nanosystem. Finite element method (FEM) calculations showed a considerable near field enhancement in NIR. Using density functional quantum chemical calculations, the chemical enhancement mechanism of rhodamine 6G by interaction with the nanoparticles was probed, allowing us to calculate spectra that closely reproduce the experimental results. The nanosystem was tested in cell culture experiments, showing cell internalization and also proving to be completely biocompatible, as no cell death was observed. Using a NIR laser, SERS signals could be detected even from inside cells, proving the applicability of this nanosystem as a biocompatible SERS probe.

Introduction: Hepatocellular carcinoma disproportionately affects minorities. Southern states have high proportions of black populations and prevalence of known risk factors. Further research is needed to understand the role of southern geography in hepatocellular carcinoma disparities. This paper examined racial disparities in hepatocellular carcinoma incidence, demographics, tumor characteristics, receipt of treatment, and all-cause mortality in southern and non-southern cancer registries., Methods: Surveillance Epidemiology and End Results data were probed in 2015 to identify 43,868 patients diagnosed with hepatocellular carcinoma from 2000 to 2012 (5,455 in southern registries [Atlanta, Louisiana, and Rural and Greater Georgia])., Results: Southern registries showed steeper increases of age-adjusted hepatocellular carcinoma incidence (from 2.89 to 5.29cases/100,000 people) versus non-southern areas (from 3.58 to 5.54cases/100,000 people). Blacks were over-concentrated in southern registries (32% vs 10%). Compared with whites, blacks were significantly younger at diagnosis, more likely diagnosed with metastasis, and less likely to receive surgical therapies in both registry groups. After adjustment, blacks had a significantly higher risk of all-cause mortality compared with whites in southern (hazard ratio=1.10, p=0.007) and non-southern areas (hazard ratio=1.08, p<0.001). For overall populations, southern registries had higher risk of all-cause mortality versus non-southern registries (hazard ratio=1.13, p<0.001)., Conclusions: Age-adjusted incidence rates of hepatocellular carcinoma are plateauing overall, but are still rising in southern areas. Race and geography had independent associations with all-cause mortality excess risk among patients with hepatocellular carcinoma. Further studies are needed to understand the root causes of potential mortality risk excess among overall populations with hepatocellular carcinoma living in the South., Supplement Information: This article is part of a supplement entitled African American Men's Health: Research, Practice, and Policy Implications, which is sponsored by the National Institutes of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Hemodialysis vascular access thrombosis is an acute event that can interrupt the dialytic treatment. A timely management can restore access patency, avoiding the use of central venous catheters and their complications., Objective: To present the experience from a Brazilian Interventional Nephrology Center (INC) in the salvage of arteriovenous fistula (AVF) and grafts for hemodialysis., Methods: A retrospective study was performed to evaluate the primary and secondary patencies of 41 hemodialysis accesses with thrombosis confirmed by ultrasound and submitted to endovascular salvage procedures. We considered clinical success the use of the access for at least 3 subsequent hemodialysis sessions. The procedures were done in an outpatient center by interventional nephrologists. Patients were followed for up to 18 months with Doppler every 3 months., Results: Forty-five salvage procedures were performed in 41 accesses of 40 hemodialysis patients with native AVF or grafts. Of these, 90% were AVF, mostly upper arm, and 10% were grafts. Clinical success rate was 60% (27 procedures). Primary patency at 12 months was 39% and secondary was 52%. Gender of the patient, diabetes, and location of the access did not correlate statistically with outcomes. There were 3 major complications (anastomosis rupture, grade 3 hematoma, and anaphylactic shock)., Conclusion: The majority of thrombosed accesses can be successfully treated, maintaining its long-term patency. The need of repeated intervention is frequent.