Long-term outcomes of catheter ablation for atrial fibrillation in octogenarians.

BACKGROUND AND AIMS: Catheter ablation is superior to pharmacological therapy in controlling atrial fibrillation (AF). There are few data on the long-term outcome of AF ablation in octogenarian patients. This analysis aims to evaluate the outcome of AF ablation in octogenarians vs. younger patients. METHODS: In this retrospective study in 13 centres in the UK, France, and Switzerland, the long-term outcomes of 473 consecutive octogenarian patients undergoing ablation for AF were compared to 473 matched younger controls (median age 81.3 [80.0, 83.0] vs. 64.4 [56.5, 70.7] years, 54.3% vs. 35.1% females; p-value for both < 0.001). The primary endpoint was the recurrence of atrial arrhythmia after a blanking period of 90 days within 365 days of follow-up. RESULTS: Acute ablation success as defined as isolation of all pulmonary veins was achieved in 97% of octogenarians. Octogenarians experienced more procedural complications (11.4% vs 7.0%, p = 0.018). The median follow-up time was 281 [106, 365] days vs. 354 [220, 365] days for octogenarians vs. non-octogenarians (p < 0.001). Among octogenarians, 27.7% (131 patients) experienced a recurrence of atrial arrhythmia, in contrast to 23.5% (111 patients) in the younger group (odds ratio 1.49; 95% confidence interval 1.16-1.92; p = 0.002). In a multivariable regression model including gender, previous AF ablation, vascular disease, chronic kidney disease, CHA2DS2-VASc score, left atrial dilatation, and indwelling cardiac implantable electronic device, age above 80 remained an independent predictor of recurrence of arrhythmia. CONCLUSION: Ablation for AF is effective in octogenarians, but is associated with slightly higher procedural complication rate and recurrence of atrial arrhythmia than in younger patients.

Fungicide resistance in Botrytis cinerea and identification of Botrytis species associated with blueberry in Michigan.

Botrytis blossom blight and fruit rot, caused by Botrytis cinerea, is a significant threat to blueberries, potentially resulting in substantial economic losses if not effectively managed. Despite the recommendation of various cultural and chemical practices to control this pathogen, there are widespread reports of fungicide resistance, leading to decreased efficacy. This study aimed to characterize the resistance profile of B. cinerea isolated from blighted blossoms and fruit in 2019, 2020 and 2022 (n = 131, 40, and 37 for the respective years). Eight fungicides (fludioxonil, thiabendazole, pyraclostrobin, boscalid, fluopyram, fenhexamid, iprodione, and cyprodinil) were tested using conidial germination at specific discriminatory doses. Additionally, 86 isolates were phylogenetically characterized using the internal transcribed spacer regions (ITS) and the protein coding genes: glyceraldehyde-3-phosphate dehydrogenase (G3PDH), heat-shock protein 60 (HSP60), and RNA polymerase II second largest subunit (RPB2). This revealed higher fungicide resistance frequencies in 2020 and 2022 compared to 2019. Over all 3 years, over 80% of the isolates were sensitive to fludioxonil, fluopyram, and fenhexamid. Pyraclostrobin and boscalid showed the lowest sensitivity frequencies (<50%). While multi-fungicide resistance was observed in all the years, none of the isolates demonstrated simultaneous resistance to all tested fungicides. Botrytis cinerea was the most prevalent species among the isolates (74) with intraspecific diversity detected by the genes. Two isolates were found to be closely related to B. fabiopsis, B. galanthina, and B. caroliniana and 10 isolates appeared to be an undescribed species. This study reports the discovery of a potentially new species sympatric with B. cinerea on blueberries in Michigan.

Role of impedance drop and lesion size index (LSI) to guide catheter ablation for atrial fibrillation.

BACKGROUND: When using lesion size index (LSI) to guide catheter ablation, it is unclear what combination of power, contact force and time would be preferable to use and what LSI target value to aim for. This study aimed at identifying desirable ablation settings and LSI targets by using tissue impedance drop as indicator of lesion formation. METHODS: Consecutive patients, undergoing their first left atrial (LA) catheter ablation for atrial fibrillation, with radiofrequency energy (RF) powers of 20, 30 and 40 W were enrolled. Tissue impedance, contact force (CF), Force Time Integral (FTI) and LSI values were continuously recorded during ablation and sampled at 100 Hz. Mean CF and Contact Force Variability (CFV) were calculated for every lesion. The effect of RF power, ablation time, CF and CFV on impedance drop and LSI were assessed. RESULTS: A total of 3258 lesions were included in the analysis. For any target LSI value, use of higher RF powers translated into progressively higher impedance drops. The impact of lower CF and higher CFV on impedance drop was more relevant when using lower powers. Target LSI values corresponding to maximum impedance drop were identified depending on RF power, mean CF and CFV used. CONCLUSIONS: Even in the context of an LSI-guided ablation strategy, use of lower or higher powers might lead to different lesion sizes. Different LSI targets might be needed depending on the combination of RF power, CF and CFV used for ablation. Incorporating indicators of catheter stability, like CFV, in the LSI formula could improve the predictive value of LSI for lesion size. Studies with clinical outcomes are required to confirm the clinical relevance of these findings.

Piloting Home Produce Delivery to Improve Food Security, Budget, and Diet in Families with Children: A Mixed-Methods Study.

BACKGROUND: Few children in food insecure (FI) households meet dietary recommendations for fruit and vegetables ("produce"). Barriers include affordability, accessibility, and desirability. Home produce delivery may reduce FI, increase produce consumption, and decrease budget tradeoffs. OBJECTIVE: Evaluate the acceptability and potential impact of delivering produce through home visiting programs on FI, diet, and budget tradeoffs. METHODS: In this prospective pre/post mixed methods study, 51 parents engaged in home visiting programs were enrolled. Participants completed pre- and post-program surveys on FI (18-item Food Security Scale), produce consumption, and budget tradeoffs. Pre- and post-surveys were compared using McNemar's test and weighted kappas. Interview guides were based on Social Cognitive Theory and a previously published framework. Interviews were conducted in English or Spanish; thematic analysis was completed. RESULTS: Twenty-nine (56.9%) participants completed both surveys. Most were female (96.3%) and Hispanic (79.3%) (Table 1). Food security improved in the post-period, with more participants reporting high food security (pre: 6.9%, post: 31.0%) and fewer reporting very low food security (pre: 20.7%, post: 6.9%, p<0.01) (Table 2). Budgetary tradeoffs decreased in the post-program period (pre: 71.4%, post: 48.1%, p=0.03). Fifteen participants were interviewed. Themes included 1) saved money, 2) increased fruit and vegetable consumption, and 3) interest in future participation. CONCLUSION: This pilot study found that an intervention for delivery of produce through home visiting programs was acceptable to participants and resulted in potential improvements in FI and household budgets. This supports future studies to further explore the impact of this novel intervention. WHAT'S NEW: In this prospective mixed-methods pilot, home delivered produce was acceptable and feasible with potentially improved food security and household budgets; evidence of potential change in produce consumption was mixed. Changes in budget tradeoffs is a novel outcome in food programs.

How to: assess patient suitability for unlicensed phage therapy in the United Kingdom.

BACKGROUND: Bacteriophage (phage) therapy is a promising alternative antimicrobial approach which has the potential to transform the way we treat bacterial infections. The antibiotic resistance crisis is driving renewed interest in phage therapy. There are currently no licenced phage therapy medicinal products and phage therapy is used in small but growing patient numbers on an unlicensed basis. OBJECTIVES: This article provides guidelines on the assessment of patient suitability for unlicensed phage therapy for clinicians in the United Kingdom. SOURCES: This article builds on Health Improvement Scotland's recommendation for the consideration of phage therapy in difficult-to-treat infection and the experience of the author group who have collectively assessed the suitability of 30 patients for phage therapy. CONTENT: In the UK, unlicensed medicines, including phages, may be considered to meet special clinical needs. The use of unlicensed medicines is governed by national legislation and local NHS Trust policies. Phages can be used in any NHS Trust and decisions about suitability should be made via existing local clinical management pathways. This article sets out guidelines to support local clinical teams in the assessment of patient suitability for phage therapy. Clinical and microbiological considerations are presented, including allergy and pregnancy.

Risk factors for raised left ventricular filling pressure by cardiovascular magnetic resonance: Prognostic insights.

BACKGROUND: Cardiovascular magnetic resonance (CMR) imaging shows promise in estimating pulmonary capillary wedge pressure (PCWP) non-invasively. At the population level, the prognostic role of CMR-modelled PCWP remains unknown. Furthermore, the relationship between CMR-modelled PCWP and established risk factors for cardiovascular disease has not been well characterized. OBJECTIVE: The main aim of this study was to investigate the prognostic value of CMR-modelled PCWP at the population level. METHODS: Employing data from the imaging substudy of the UK Biobank, a very large prospective population-based cohort study, CMR-modelled PCWP was calculated using a model incorporating left atrial volume, left ventricular mass and sex. Logistic regression explored the relationships between typical cardiovascular risk factors and raised CMR-modelled PCWP (≥15 mmHg). Cox regression was used to examine the impact of typical risk factors and CMR-modelled PCWP on heart failure (HF) and major adverse cardiovascular events (MACE). RESULTS: Data from 39 163 participants were included in the study. Median age of all participants was 64 years (inter-quartile range: 58 to 70), and 47% were males. Clinical characteristics independently associated with raised CMR-modelled PCWP included hypertension [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.44-1.70, P < 0.001], body mass index (BMI) [OR 1.57, 95% CI 1.52-1.62, per standard deviation (SD) increment, P < 0.001], male sex (OR 1.37, 95% CI 1.26-1.47, P < 0.001), age (OR 1.33, 95% CI 1.27-1.41, per decade increment, P < 0.001) and regular alcohol consumption (OR 1.10, 95% CI 1.02-1.19, P = 0.012). After adjusting for potential confounders, CMR-modelled PCWP was independently associated with incident HF [hazard ratio (HR) 2.91, 95% CI 2.07-4.07, P < 0.001] and MACE (HR 1.48, 95% CI 1.16-1.89, P = 0.002). CONCLUSIONS: Raised CMR-modelled PCWP is an independent risk factor for incident HF and MACE. CMR-modelled PCWP should be incorporated into routine CMR reports to guide HF diagnosis and further management.

Understanding the deficiency in inertial confinement fusion hohlraum x-ray flux predictions using experiments at the National Ignition Facility.

The predicted implosion performance of deuterium-tritium fuel capsules in indirect-drive inertial confinement fusion experiments relies on precise calculations of the x-ray drive in laser-heated cavities (hohlraums). This requires accurate, spectrally dependent simulations of laser to x-ray conversion efficiencies and x-ray absorption losses to the hohlraum wall. A set of National Ignition Facility experiments have identified a cause for the long-standing hohlraum "drive deficit" as the overprediction of gold emission at ∼2.5 keV in nonlocal thermodynamic equilibrium coronal plasma regions within the hohlraum. Reducing the emission and absorption opacity in this spectral region by ∼20% brings simulations into agreement with measured x-ray fluxes and spectra.

Perspectives on Online Resources for People Experiencing Pain: A Qualitative Study.

BACKGROUND: Innovations in technology offer potential solutions to address pain care inequities. To maximize impacts, greater understanding is needed regarding preferences and priorities of people experiencing or treating pain. OBJECTIVES: This study conducted focus groups to investigate the perspectives of people with pain and healthcare workers regarding online resources for pain management. Researchers asked about barriers to current pain management and what resources would be most desired in an online format to meet needs. METHODS: Participants were a randomly selected sub-sample of adults from a northwestern region of the United States who participated in an online, survey-based study. Eligible participants identified as either a person who had received treatment for pain or a healthcare worker who cared for people with pain. Of the 199 survey respondents, 30 participated in one of three focus group sessions. Focus groups were conducted using videoconferencing technology, then recorded, transcribed, and analyzed using thematic analysis. RESULTS: Focus group participants included 22 adults who identified as a person treated for pain of any type and 8 healthcare workers. Themes relating to eHealth use reflected desires for (1) freely accessible and vetted pain management information in one place, (2) reliable information tailored to need and pain type, and (3) easy-to-use resources. Findings revealed that some effective pain management resources do exist, yet obstacles including inflexible and inequitable healthcare practices and lack of knowledge about options may limit access to these resources. CONCLUSION: Including preferences of user groups can assist in creating resources that are likely to be useful for those with pain and their caregivers. Innovations are needed to address persisting gaps in care.

Light Activated Release of Nitrile Ligands from trans-Ru(L)(PPh3)2(nitrile) Complexes.

A series of trans-RuL(PPh3)2(nitrile) and {RuL(PPh3)2}.2-µ-(nitrile)-based complexes [where L = 2,2'-(3,4-diphenyl-pyrrole-2,5-diyl)dipyridine (dpp), di(pyridin-2-yl)isoindoline-1,3-diimine (bpi), or 4-(4-methoxyphenyl)-6-phenyl-2,2'-bipyridine (Pbpy); and nitrile = 1,4-dibenzontirile, 4-ethynylbenzonitrile, or dicyanamide] were synthesized and characterized, and their electrochemical and photochemical behaviors were investigated. Those complexes that contained a significant nitrile contribution to their 3MLLCT show a release of their nitrile ligand (when L = dpp or Pbpy and the nitrile ligand = 4-dibenzontirile, or 4-ethynylbenzonitrile) with dissociation constants up to 8.09 × 10-4 s-1.

Messages About Tobacco and Alcohol Co-users.

OBJECTIVE: People who use both alcohol and combustible tobacco have an increased risk of developing cancer. Few interventions have been developed to inform people about the risks of co-use. This study developed and tested messages about the risks of alcohol and combustible tobacco co-use among adults. METHOD: In June-July 2021, we surveyed 1,300 U.S. adults who used both alcohol and combustible tobacco products within the past 30 days. After reporting their awareness of diseases caused by tobacco and alcohol co-use, participants were randomly assigned to four between-subjects experiments that manipulated specific cancer health effects vs. the word "cancer"; cancer health effects vs. noncancer health effects; different descriptions of co-use (e.g., Using alcohol and tobacco…, Drinking alcohol and smoking tobacco…); and co-use vs. single-use messages. Participants saw one message for each experiment and rated each message using a validated perceived message effectiveness (PME) scale. RESULTS: Awareness of health effects caused by alcohol and tobacco co-use ranged from moderately high for throat cancer (65.4%) to moderately low for colorectal cancer (23.1%). Messages about cancer health effects increased PME more than messages about non-cancer health effects (B=0.18, p=0.01). Messages about some specific cancers-including oral cancer (B=-0.20, p=0.04) and colorectal cancer (B=-0.22, p=0.02) decreased PME more than messages with only the word "cancer." No significant differences were identified for descriptions of co-use or co-use vs. single-use messages. CONCLUSIONS: Messages about some cancer health effects of co-using alcohol and tobacco may be effective when communicating the harms of both drinking alcohol and using tobacco.

Mapping TB incidence across districts in Uganda to inform health program activities.

BACKGROUND: Identifying spatial variation in TB burden can help national TB programs effectively allocate resources to reach and treat all people with TB. However, data limitations pose challenges for subnational TB burden estimation. METHODS: We developed a small-area modeling approach using geo-positioned prevalence survey data, case notifications, and geospatial covariates to simultaneously estimate spatial variation in TB incidence and case notification completeness across districts in Uganda from 2016-2019. TB incidence was estimated using 1) cluster-level data from the national 2014-2015 TB prevalence survey transformed to incidence, and 2) case notifications adjusted for geospatial covariates of health system access. The case notification completeness surface was fit jointly using observed case notifications and estimated incidence. RESULTS: Estimated pulmonary TB incidence among adults varied >10-fold across Ugandan districts in 2019. Case detection increased nationwide from 2016 to 2019, and the number of districts with case detection rates >70% quadrupled. District-level estimates of TB incidence were five times more precise than a model using TB prevalence survey data alone. CONCLUSION: A joint spatial modeling approach provides useful insights for TB program operation, outlining areas where TB incidence estimates are highest and health programs should concentrate their efforts. This approach can be applied in many countries with high TB burden.

CONTEXTE: L'identification des variations spatiales de la charge de morbidité de la TB peut aider les programmes nationaux de lutte contre la TB à allouer efficacement les ressources pour atteindre et traiter toutes les personnes atteintes de TB. Cependant, les limites des données posent des problèmes pour l'estimation de la charge de morbidité infranationale. MÉTHODES: Nous avons développé une approche de modélisation à petite échelle en utilisant des données d'enquête de prévalence géolocalisées, des notifications de cas et des covariables géospatiales pour estimer simultanément la variation spatiale de l'incidence de la TB et l'exhaustivité de la notification des cas dans les districts de l'Ouganda de 2016 à 2019. L'incidence de la TB a été estimée à l'aide 1) des données au niveau des grappes de l'enquête nationale sur la prévalence de la TB de 2014­2015, transformées en incidence, et 2) des notifications de cas ajustées pour tenir compte des covariables géospatiales de l'accès au système de santé. La surface de complétude des notifications de cas a été ajustée conjointement à l'aide des notifications de cas observés et de l'incidence estimée. RÉSULTATS: L'incidence estimée de la TB pulmonaire chez les adultes a été multipliée par >10 dans les districts ougandais en 2019. La détection des cas a augmenté à l'échelle nationale entre 2016 et 2019, et le nombre de districts avec des taux de détection des cas >70% a quadruplé. Les estimations de l'incidence de la TB au niveau des districts étaient cinq fois plus précises qu'un modèle utilisant uniquement les données de l'enquête sur la prévalence de la TB. CONCLUSION: Une approche conjointe de modélisation spatiale fournit des informations utiles pour le fonctionnement des programmes de lutte contre la TB, en décrivant les domaines où les estimations de l'incidence de la TB sont les plus élevées et où les programmes de santé devraient concentrer leurs efforts. Cette approche peut être appliquée dans de nombreux pays où la charge de morbidité de la TB est élevée.

On-Demand Thio-Succinimide Hydrolysis for the Assembly of Stable Protein-Protein Conjugates.

Chemical post-translational protein-protein conjugation is an important technique with growing applications in biotechnology and pharmaceutical research. Maleimides represent one of the most widely employed bioconjugation reagents. However, challenges associated with the instability of first- and second-generation maleimide technologies are yet to be fully addressed. We report the development of a novel class of maleimide reagents that can undergo on-demand ring-opening hydrolysis of the resulting thio-succinimide. This strategy enables rapid post-translational assembly of protein-protein conjugates. Thio-succinimide hydrolysis, triggered upon application of chemical, photochemical, or enzymatic stimuli, allowed homobifunctional bis-maleimide reagents to be applied in the production of stable protein-protein conjugates, with complete temporal control. Bivalent and bispecific protein-protein dimers constructed from small binders targeting antigens of oncological importance, PD-L1 and HER2, were generated with high purity, stability, and improved functionality compared to monomeric building blocks. The modularity of the approach was demonstrated through elaboration of the linker moiety through a bioorthogonal propargyl handle to produce protein-protein-fluorophore conjugates. Furthermore, extending the functionality of the homobifunctional reagents by temporarily masking reactive thiols included in the linker allowed the assembly of higher order trimeric and tetrameric single-domain antibody conjugates. The potential for the approach to be extended to proteins of greater biochemical complexity was demonstrated in the production of immunoglobulin single-domain antibody conjugates. On-demand control of thio-succinimide hydrolysis combined with the facile assembly of chemically defined homo- and heterodimers constitutes an important expansion of the chemical methods available for generating stable protein-protein conjugates.

Evaluation of deep-learning TSE images in clinical musculoskeletal imaging.

In this study, we compared the fat-saturated (FS) and non-FS turbo spin echo (TSE) magnetic resonance imaging knee sequences reconstructed conventionally (conventional-TSE) against a deep learning-based reconstruction of accelerated TSE (DL-TSE) scans. A total of 232 conventional-TSE and DL-TSE image pairs were acquired for comparison. For each consenting patient, one of the clinically acquired conventional-TSE proton density-weighted sequences in the sagittal or coronal planes (FS and non-FS), or in the axial plane (non-FS), was repeated using a research DL-TSE sequence. The DL-TSE reconstruction resulted in an image resolution that increased by at least 45% and scan times that were up to 52% faster compared to the conventional TSE. All images were acquired on a MAGNETOM Vida 3T scanner (Siemens Healthineers AG, Erlangen, Germany). The reporting radiologists, blinded to the acquisition time, were requested to qualitatively compare the DL-TSE against the conventional-TSE reconstructions. Despite having a faster acquisition time, the DL-TSE was rated to depict smaller structures better for 139/232 (60%) cases, equivalent for 72/232 (31%) cases and worse for 21/232 (9%) cases compared to the conventional-TSE. Overall, the radiologists preferred the DL-TSE reconstruction in 124/232 (53%) cases and stated no preference, implying equivalence, for 65/232 (28%) cases. DL-TSE reconstructions enabled faster acquisition times while enhancing spatial resolution and preserving the image contrast. From these results, the DL-TSE provided added or comparable clinical value and utility in less time. DL-TSE offers the opportunity to further reduce the overall examination time and improve patient comfort with no loss in diagnostic accuracy.

Two cases of silent subcutaneous implantable cardioverter defibrillator electrode displacement.

We describe two cases of secondary prevention subcutaneous implantable cardioverter defibrillator (S-ICD) implantation and subsequent S-ICD electrode displacement which initially went undetected. One presentation was a result of a coincidental chest x-ray for respiratory exacerbation and another with an untreated episode highlighted via remote monitoring, both patients were booked to clinic for further investigation. Our findings highlighted had there been a comparison of the existing subcutaneous electrogram (S-ECG) to captured S-ECGs at time of implant the electrode displacement would have been detected beforehand. This underpins the importance of introducing the simple management strategy into routine follow-up.

Microglia protect against age-associated brain pathologies.

Microglia are brain-resident macrophages that contribute to central nervous system (CNS) development, maturation, and preservation. Here, we examine the consequences of permanent microglial deficiencies on brain aging using the Csf1rΔFIRE/ΔFIRE mouse model. In juvenile Csf1rΔFIRE/ΔFIRE mice, we show that microglia are dispensable for the transcriptomic maturation of other brain cell types. By contrast, with advancing age, pathologies accumulate in Csf1rΔFIRE/ΔFIRE brains, macroglia become increasingly dysregulated, and white matter integrity declines, mimicking many pathological features of human CSF1R-related leukoencephalopathy. The thalamus is particularly vulnerable to neuropathological changes in the absence of microglia, with atrophy, neuron loss, vascular alterations, macroglial dysregulation, and severe tissue calcification. We show that populating Csf1rΔFIRE/ΔFIRE brains with wild-type microglia protects against many of these pathological changes. Together with the accompanying study by Chadarevian and colleagues1, our results indicate that the lifelong absence of microglia results in an age-related neurodegenerative condition that can be counteracted via transplantation of healthy microglia.

Antidepressant-associated diagnostic change from major depressive to bipolar disorder.

BACKGROUND: Anticipating diagnostic change from major depressive (MDD) to bipolar disorder (BD) can support better prognosis and treatment, especially of depression but is challenging and reported research results are inconsistent. We therefore assessed clinical characteristics associated with diagnostic change from MDD to BD with antidepressant treatments. METHODS: We compared characteristics of 3212 initially MDD patients who became (hypo)manic during antidepressant treatment to those with stable MDD diagnoses as well as with cases of stable, spontaneous BD, using standard bivariate and multivariate statistics. RESULTS: Among MDD patients, 6.69% [CI: 5.85-7.61] changed to BD, mostly type II (BD2, 76.7%). BD-converters had higher rates of familial mood disorders (74.1% vs. 57.1%) or BD (33.7% vs. 21.0%) and 2.8-years younger onset than stable MDD patients. They also had more prior depressive recurrences/year, years-of-illness, mood-stabilizer treatment, divorces, fewer children, more suicide attempts and drug-abuse, and higher intake cyclothymia, YMRS and MDQ scores. Predictors independently associated with diagnostic conversion were: more familial BD, depressions/year, unemployment, cyclothymic temperament, suicidal ideation or acts, and fewer children. BD-converters vs. spontaneous BD cases had significantly more suicide attempts, BD2 diagnoses, and affected relatives. Converting to vs. spontaneous BD1 was associated with more ADHD, more suicidal ideation or behavior, MDI course, and younger onset; converting to vs. spontaneous BD2 had more episodes/year, unemployment, ADHD, substance abuse, suicidal ideation or attempts, and more relatives with BD. CONCLUSIONS: Few (6.69%) initially MDD subjects converted to BD, most (76.7%) to BD2. Independent predictive associations with diagnostic change included: familial BD, more depressions/year, unemployment, cyclothymic temperament, suicidal behavior and fewer children. Notably, several characteristics were stronger among those changing to BD during antidepressant treatment vs. others with spontaneous BD.

Evaluating the effect of direct-acting antiviral agent treatment scale-up on Hepatitis C virus prevalence among people who inject drugs in UK.

BACKGROUND: There is limited empirical work assessing the effectiveness of treatment as prevention (TasP) in reducing HCV prevalence among people who inject drugs (PWID). Here, we used survey data from the UK during 2010-2020, to evaluate the impact of direct-acting antiviral agent (DAA) treatment scale-up, which started in 2015, on HCV prevalence among PWID. METHODS: We fitted a logistic regression to time/location specific data on prevalence from the Needle Exchange Surveillance Initiative in Scotland and Unlinked Anonymous Monitoring programme in England. For each post-intervention year and location, we quantified the effect of TasP as the difference between estimated prevalence and its counterfactual (prevalence in the absence of scale-up). Progress to elimination was assessed by comparing most recent prevalence against one in 2015. RESULTS: In 2015, prevalence ranged from 0.44 to 0.71 across the 23 locations (3 Scottish, 20 English). Compared to counterfactuals, there was an absolute reduction of 46% (95% credible interval [32%,59%]) in Tayside in 2020, 35% ([24%,44%]) in Glasgow in 2019, and 25% ([10%,39%]) in the Rest of Scotland in 2020. The English sites with highest estimated absolute reductions in 2021 were South Yorkshire (45%, [29%,58%]), Thames Valley (49%, [34%,59%]) and West London (41%, [14%,59%]). Compared to 2015, there was 80% probability that prevalence had fallen by 65% in Tayside, 53% in Glasgow and 36% in the Rest of Scotland. The English sites with highest % prevalence decrease compared to 2015, achieved with probability 80%, were Chesire & Merseyside (70%), South Yorkshire (65%) and Thames Valley (71%). Higher treatment intensity was associated with higher reductions in prevalence. CONCLUSION: Conclusion. Real-world evidence showing substantial reductions in chronic HCV associated with increase of HCV treatment scale-up in the community thus supporting the effectiveness of HCV treatmen as prevention in people who inject drugs.

Sustainable Calcite Scale Inhibitors via Oxidation of Lignosulfonates.

Deposition of inorganic scales in wells, flow lines, and equipment is a major problem in the water treatment, geothermal, or upstream oil and gas industries. Deployment of scale inhibitors has been adopted worldwide for oilfield scale prevention. Commercial synthetic scale inhibitors such as polymeric carboxylates and sulfonates or nonpolymeric phosphonates offer good scale inhibition performance but often suffer from one or more limitations including biodegradability, calcium compatibility, and thermal stability. Lignin-based biomaterials such as sodium lignosulfonates are natural, sustainable, and widely available polymers that are accepted for use in environmentally sensitive areas. Here we show that, although lignosulfonates perform relatively poorly as calcite scale inhibitors in dynamic tube blocking tests, oxidized lignosulfonates show a much improved inhibition effect by a factor of 20-fold. The oxidized lignosulfonates are easy to prepare in a 1-step reaction and show excellent calcium compatibility and thermal stability, useful for downhole squeeze treatments in high temperature wells. This present study unequivocally establishes oxidized lignosulfonates as a new class of sustainable green scale inhibitors, thereby bridging the gap between materials derived directly from nature and the classic synthetic polymeric scale inhibitors.