Predictive health monitoring: Leveraging artificial intelligence for early detection of infectious diseases in nursing home residents through discontinuous vital signs analysis.

This research addresses the problem of detecting acute respiratory, urinary tract, and other infectious diseases in elderly nursing home residents using machine learning algorithms. The study analyzes data extracted from multiple vital signs and other contextual information for diagnostic purposes. The daily data collection process encounters sampling constraints due to weekends, holidays, shift changes, staff turnover, and equipment breakdowns, resulting in numerous nulls, repeated readings, outliers, and meaningless values. The short time series generated also pose a challenge to analysis, preventing the extraction of seasonal information or consistent trends. Blind data collection results in most of the data coming from periods when residents are healthy, resulting in excessively imbalanced data. This study proposes a data cleaning process and then builds a mechanism that reproduces the basal activity of the residents to improve the classification of the disease. The results show that the proposed basal module-assisted machine learning techniques allow anticipating diagnostics 2, 3 or 4 days before doctors decide to start treatment with antibiotics, achieving a performance measured by the area-under-the-curve metric of 0.857. The contributions of this work are: (1) a new data cleaning process; (2) the analysis of contextual information to improve data quality; (3) the generation of a baseline measure for relative comparison; and (4) the use of either binary (disease/no disease) or multiclass classification, differentiating among types of infections and showing the advantages of multiclass versus binary classification. From a medical point of view, the anticipated detection of infectious diseases in institutionalized individuals is brand new.

Histological Findings in the Eyes of Abcc6 Knockout Rat Model of Pseudoxanthoma Elasticum.

Purpose: To describe the ocular findings of murine pseudoxanthoma elasticum (PXE) models with ATP-binding cassette subfamily C member 6 (Abcc6) gene knockout. Methods: This experiment was conducted in four Abcc6-/- rats and compared with six wild-type Abcc6+/+ control rats. The animals underwent necropsy at 6 months of age. Histological examination of the eyes was performed. Results: Histological examination of eight eyes from four Abcc6-/- rats revealed multiple nodular foci of calcification in the uvea, sclera, and conjunctiva, focally in perivascular distribution, as well as linear and nodular calcification of Bruch's membrane. Calcific foci were not associated with inflammation in the knockout rats. There was no evidence of calcification in control eyes. Discussion: The Abcc6-/- rat model shows that PXE can affect multiple ocular tissues beyond the calcification in Bruch's membrane noted in human eyes. Nodular calcific foci probably correspond to comet lesions seen in patients with PXE. The presence of ectopic calcium without inflammation distinguishes it from inflammatory calcium deposition in atherosclerosis. Further studies are needed to determine why PXE does not cause inflammatory infiltration. Translational Relevance: The Abcc6-/- murine model may be suitable for studying ocular PXE pathophysiology and ectopic calcification and developing effective therapies.

Pseudoxanthoma elasticum-associated angioid streaks near a scleral buckle.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

New forays into measurement of ocular biomechanics.

PURPOSE OF REVIEW: The field of corneal biomechanics has rapidly progressed in recent years, reflecting technological advances and an increased understanding of the clinical significance of measuring these properties. This review will evaluate in-vivo biomechanical properties obtained by current technologies and compare them regarding their relevance to established biomechanical properties obtained by gold-standard ex-vivo techniques normally conducted on elastic materials. RECENT FINDINGS: Several new technologies have appeared in recent years, including vibrational optical coherence tomography (VOCT) and the corneal indentation device (CID). These techniques provide promising new opportunities for minimally invasive and accurate measurements of corneal viscoelastic properties. SUMMARY: Alterations in corneal biomechanics are known to occur in several corneal degenerative diseases and after refractive surgical procedures. The measurement of corneal biomechanical properties has the capability to diagnose early disease and monitor corneal disease progression. Several new technologies have emerged in recent years, allowing for more accurate and less invasive measurements of corneal biomechanical properties, most notably the elastic modulus.

Genetic analysis of ocular tumour-associated genes using large genomic datasets: insights into selection constraints and variant representation in the population.

BACKGROUND: Large genomic databases enable genetic evaluation in terms of haploinsufficiency and prevalence of missense and synonymous variants. We explored these parameters in ocular tumour-associated genes. METHODS: A curated list of ocular tumour-associated genes was assessed using the genomic databases Genome Aggregation Database (gnomAD) and DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) and compared with breast and lung cancer-associated gene lists. Haploinsufficiency was determined based on specific criteria: probability of loss of function index ≥0.9 in gnomAD, upper CI O/E limit <0.35 for loss of function variants in gnomAD and/or a DECIPHER pHaplo ≥0.86. UniProt was used for further gene characterisation, and gene ontology Protein Analysis THrough Evolutionary Relationships was explored for common biological pathways. In addition, we identified genes with under-representation/over-representation of missense/synonymous variants. RESULTS: Fifty-seven genes were identified in association with ocular and extraocular tumours.Regarding haploinsufficiency, 41% of genes met the criteria for negative selection, with 57% categorised as tumour-suppressing and 39% as oncogenic. Most genes were involved in regulatory processes. Regarding triplosensitivity, 33% of genes reached significance and 83% of these were haploinsufficient. Analysis of variants revealed under-representation of missense variants in 23% of genes and over-representation of synonymous variants in 5% of genes. Ocular tumour-associated genes exhibited higher scores for haploinsufficiency and triplosensitivity compared with breast and lung cancer-associated genes. Pathway analysis revealed significant enrichment in cellular proliferation, differentiation and division. Encoded proteins of ocular tumour-associated genes were generally longer than the median of the UniProt database. CONCLUSION: Our findings highlight the importance of negative selection in ocular tumour genes, supporting cranial gene conservation. This study provides insights into ocular tumourigenesis and future research avenues.

Challenging the Limits of Binarization: A New Scheme Selection Policy Using Reinforcement Learning Techniques for Binary Combinatorial Problem Solving.

In this study, we introduce an innovative policy in the field of reinforcement learning, specifically designed as an action selection mechanism, and applied herein as a selector for binarization schemes. These schemes enable continuous metaheuristics to be applied to binary problems, thereby paving new paths in combinatorial optimization. To evaluate its efficacy, we implemented this policy within our BSS framework, which integrates a variety of reinforcement learning and metaheuristic techniques. Upon resolving 45 instances of the Set Covering Problem, our results demonstrate that reinforcement learning can play a crucial role in enhancing the binarization techniques employed. This policy not only significantly outperformed traditional methods in terms of precision and efficiency, but also proved to be extensible and adaptable to other techniques and similar problems. The approach proposed in this article is capable of significantly surpassing traditional methods in precision and efficiency, which could have important implications for a wide range of real-world applications. This study underscores the philosophy behind our approach: utilizing reinforcement learning not as an end in itself, but as a powerful tool for solving binary combinatorial problems, emphasizing its practical applicability and potential to transform the way we address complex challenges across various fields.

Detection of TTR Amyloid in the Conjunctiva Using a Novel Fluorescent Ocular Tracer.

Background: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Methods: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. Results: AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. Conclusions: AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. Translational Relevance: AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.

El uso diario de la profilaxis preexposición para el VIH en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en España: prevalencia y factores asociados / Daily use of HIV pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Spain: Prevalence and associated factors

Objetivo: Estimar la prevalencia de uso diario de profilaxis preexposición (PrEP) frente al VIH 6 meses después de aprobarse su financiación pública en España e identificar los factores asociados en una muestra nacional de hombres gais, bisexuales y otros hombres que tienen sexo con hombres (GBHSH). Material y métodos: Se analizaron 4.692 hombres GBHSH no diagnosticados de VIH reclutados mediante un cuestionario online difundido a nivel nacional a través de apps y webs de contacto gay entre mayo y julio de 2020. Se estimó la proporción de participantes que usaban PrEP diaria y se identificaron factores asociados mediante regresión de Poisson con variancia robusta. Resultados: El 2,8% (IC 95% 2,3-3,3) de los participantes refirió usar PrEP diariamente. El uso diario de PrEP se asoció de forma independiente con: haber sido reclutado en programas comunitarios, ser mayor de 30 años, residir en grandes ciudades, vivir abiertamente su vida sexual con hombres, haber tenido relaciones anales sin preservativo con más de 10 parejas sexuales, haber consumido drogas para sexo, especialmente drogas chemsex, y haber sido diagnosticado de alguna infección de transmisión sexual. Conclusión: Transcurridos 6 meses desde la aprobación de la PrEP en España, se observa una baja prevalencia de uso diario en una muestra nacional de hombres GBHSH. Es necesario promover el acceso, la demanda y el interés por la PrEP, especialmente entre los hombres GBHSH jóvenes, residentes en ciudades pequeñas y medianas y los que ocultan sus relaciones con otros hombres.(AU)

Objective: We aim to estimate the prevalence of daily HIV pre-exposure prophylaxis (PrEP) use 6 months after public funding approval in Spain and identify associated factors in a national sample of gay, bisexual and other men who have sex with men (GBMSM). Material and methods: We analysed 4692 HIV-undiagnosed GBMSM men recruited via an online questionnaire distributed nationally via gay contact apps and websites between May and July 2020. We estimated the proportion of participants using daily PrEP and identified associated factors using Poisson regression with robust variance. Results: Daily PrEP use was reported by 2.8% (95% CI 2.3-3.3) of all participants. Daily PrEP use was independently associated with being recruited into community programmes, being older than 30 years, living in a large city, living with men, having condomless anal intercourse with more than 10 sexual partners, using drugs for sex, especially chemsex drugs, and being diagnosed with a sexually transmitted infection. Conclusion: Six months after PrEP was approved in Spain, the prevalence of daily use is low in a national sample of GBMSM men. There is a need to promote access, demand and interest in PrEP, especially among young GBMSM men, those living in small and medium-sized cities, and those who hide their relationships with other men.(AU)

Excess Mortality During 2020 in Spain: The Most Affected Population, Age, and Educational Group by the COVID-19 Pandemic.

OBJECTIVE: The objective of this work was to study mortality increase in Spain during the first and second academic semesters of 2020, coinciding with the first 2 waves of the Covid-19 pandemic; by sex, age, and education. METHODS: An observational study was carried out, using linked populations and deaths' data from 2017 to 2020. The mortality rates from all causes and leading causes other than Covid-19 during each semester of 2020, compared to the 2017-2019 averages for the same semester, was also estimated. Mortality rate ratios (MRR) and differences were used for comparison. RESULTS: All-cause mortality rates increased in 2020 compared to pre-covid, except among working-age, (25-64 years) highly-educated women. Such increases were larger in lower-educated people between the working age range, in both 2020 semesters, but not at other ages. In the elderly, the MMR in the first semester in women and men were respectively, 1.14, and 1.25 among lower-educated people, and 1.28 and 1.23 among highly-educated people. In the second semester, the MMR were 1.12 in both sexes among lower-educated people and 1.13 in women and 1.16 in men among highly-educated people. CONCLUSION: Lower-educated people within working age and highly-educated people at older ages showed the greatest increase in all-cause mortality in 2020, compared to the pre-pandemic period.

Reliability and accuracy of artificial intelligence ChatGPT in providing information on ophthalmic diseases and management to patients.

PURPOSE: To assess the accuracy of ophthalmic information provided by an artificial intelligence chatbot (ChatGPT). METHODS: Five diseases from 8 subspecialties of Ophthalmology were assessed by ChatGPT version 3.5. Three questions were asked to ChatGPT for each disease: what is x?; how is x diagnosed?; how is x treated? (x = name of the disease). Responses were graded by comparing them to the American Academy of Ophthalmology (AAO) guidelines for patients, with scores ranging from -3 (unvalidated and potentially harmful to a patient's health or well-being if they pursue such a suggestion) to 2 (correct and complete). MAIN OUTCOMES: Accuracy of responses from ChatGPT in response to prompts related to ophthalmic health information in the form of scores on a scale from -3 to 2. RESULTS: Of the 120 questions, 93 (77.5%) scored ≥ 1. 27. (22.5%) scored ≤ -1; among these, 9 (7.5%) obtained a score of -3. The overall median score amongst all subspecialties was 2 for the question "What is x", 1.5 for "How is x diagnosed", and 1 for "How is x treated", though this did not achieve significance by Kruskal-Wallis testing. CONCLUSIONS: Despite the positive scores, ChatGPT on its own still provides incomplete, incorrect, and potentially harmful information about common ophthalmic conditions, defined as the recommendation of invasive procedures or other interventions with potential for adverse sequelae which are not supported by the AAO for the disease in question. ChatGPT may be a valuable adjunct to patient education, but currently, it is not sufficient without concomitant human medical supervision.

Osteogenic organoid for bone regeneration: Healing of bone defect in congenital pseudoarthrosis of the tibia.

BACKGROUND: Congenital pseudoarthrosis of the tibia (CPT) is an uncommon disease associated with failure to achieve bone union and recurrent fractures. There is evidence showing that CPT is associated with decreased osteogenesis. Based on the capacity of mesenchymal stromal cells (MSCs) to induce osteogenesis, we develop an osteogenic organoid (OstO) constituted by these cells, and other components of the bone niche, for inducing bone formation in a child diagnosed with CPT. AIM: To evaluate the capacity of an OstO to induce bone formation in a patient with CPT. METHODS: The OstO was fabricated with allogeneic bone marrow MSCs from a healthy donor, collagen microbeads (CM) and PRP clot. The CM and PRP function as extracellular matrix and scaffolds for MSC. The OstO was placed at the site of non-union. Internal and external fixation was placed in the tibia. Radiological evaluation was performed after MSCs transplantation. RESULTS: After 4 months of MSCs transplantation, radiographic imaging showed evidence of osteogenesis at the site of CPT lesion. The tibia showed bone consolidation and complete healing of the non-union CPT lesion after 6 months. Functional improvement was observed after 1 year of MSC transplantation. CONCLUSIONS: The OstO is a bone-like niche which promote osteogenesis in patients with failure in bone formation, such as CPT. To our knowledge, these results provide the first evidence showing CPT healing induced by an OstO constituted by allogeneic MSCs. Future studies incorporating a larger number of patients may confirm these results.

Daily use of HIV pre-exposure prophylaxis among gay, bisexual and other men who have sex with men in Spain: Prevalence and associated factors. / El uso diario de la profilaxis preexposición para el VIH en hombres gais, bisexuales y otros hombres que tienen sexo con hombres en España: prevalencia y factores asociados.

OBJECTIVE: We aim to estimate the prevalence of daily HIV pre-exposure prophylaxis (PrEP) use 6 months after public funding approval in Spain and identify associated factors in a national sample of gay, bisexual and other men who have sex with men (GBMSM). MATERIAL AND METHODS: We analysed 4692 HIV-undiagnosed GBMSM men recruited via an online questionnaire distributed nationally via gay contact apps and websites between May and July 2020. We estimated the proportion of participants using daily PrEP and identified associated factors using Poisson regression with robust variance. RESULTS: Daily PrEP use was reported by 2.8% (95% CI 2.3-3.3) of all participants. Daily PrEP use was independently associated with being recruited into community programmes, being older than 30 years, living in a large city, living with men, having condomless anal intercourse with more than 10 sexual partners, using drugs for sex, especially chemsex drugs, and being diagnosed with a sexually transmitted infection. CONCLUSION: Six months after PrEP was approved in Spain, the prevalence of daily use is low in a national sample of GBMSM men. There is a need to promote access, demand and interest in PrEP, especially among young GBMSM men, those living in small and medium-sized cities, and those who hide their relationships with other men.

RIDGE-SHAPED PERIPAPILLA.

PURPOSE: To report a case of peripapillary subretinal fluid associated with a ridge-shaped morphology surrounding the optic disk, which we termed ridge-shaped peripapilla. METHODS: Case report. RESULTS: A 6-year-old girl with mild-to-moderate myopia was referred for an abnormal fundus appearance of the left eye. Fundus examination of the left eye showed a vertical whitish elevation just temporal to the disk with pigment clumping. Spectral domain optical coherence tomography of the left eye showed an elevation of the fundus at the temporal edge of the disk with thinning of the choroid overlying the thickened scleral protrusion and a serous subretinal fluid. Fluorescein angiography of the left eye showed a hyperfluorescent area without leakage at the temporal edge of the disk, indicative of retinal pigment epithelium atrophy. There was no sign of choroidal neovascularization. Based on the fluorescein angiography and optical coherence tomography findings, the protrusion of the sclera seemed to result in overlying choroidal thinning with choroidal blood flow disturbances, and consequent retinal pigment epithelium atrophy, leading to the subretinal fluid. CONCLUSION: This case highlights an unusual presentation of ridge-shaped peripapilla, characterized by inward convexity of the peripapillary area with a ridge-shaped morphology and localized thickening of the peripapillary sclera, in eyes with myopia.

Instances of ocular findings in transgender patients undergoing hormonal therapy.

Purpose: To describe the ophthalmological manifestations in transgender patients on gender-affirming hormone therapy. Methods: A retrospective chart review study was conducted. Female-to-male (FTM) and male-to-female (MTF) transgenders on gender-affirming hormone therapy evaluated at a single center were included. Candidates were collected using a phrase-identifying search tool within the electronic medical record system. Descriptive analyses were conducted to report the demographics, hormonal therapies, clinical findings, and visual outcomes. Results: A total of 17 patients were included, seven were FTM, and ten were MTF transgenders. The median age was 26.0 years (range; 20.0-30.0) in the FTM group and 35.0 years (range; 23.0-67.0) in the MTF group. Testosterone therapy in FTM patients comprised 30-60 mg of intramuscular injections weekly or 50 mg of transdermal gel daily. MTF patients used mainly 2-4 mg of estradiol and 100-300 mg of spironolactone tablets daily. A total of 27 eyes were affected, 12 in FTM and 15 in MTF patients. The median visual acuity was 20/25 in FTM (range; 20/20-20/60) and 20/25 in MTF (range; 20/20-20/400). The most common diagnoses in FTM patients were neurologic (71.4 %), particularly idiopathic intracranial hypertension, while MTF transgenders presented mainly with chorioretinal diseases (40.0 %). Compliance with medical recommendations and follow-up appointments was seen in 71.4 % of FTM and 50.0 % of MTF patients. At the last visit, the median visual acuity was 20/50 (range; 20/20-20/70) in FTM and 20/25 (range; 20/20-20/70) in MTF patients. Conclusions and importance: Transgenders presented a variety of ocular findings. A cause-and-effect association cannot be stated, yet eye specialists must be cognizant of these findings to provide appropriate treatment.

Association of Circulating Antiretinal Antibodies With Clinical Outcomes in Retinitis Pigmentosa.

Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.

Random Allelic Expression in Inherited Retinal Disease Genes.

Inherited retinal diseases (IRDs) are a significant contributor to visual loss in children and young adults, falling second only to diabetic retinopathy. Understanding the pathogenic mechanisms of IRDs remains paramount. Some autosomal genes exhibit random allelic expression (RAE), similar to X-chromosome inactivation. This study identifies RAE genes in IRDs. Genes in the Retinal Information Network were cross-referenced with the recent literature to identify expression profiles, RAE, or biallelic expression (BAE). Loss-of-function intolerance (LOFI) was determined by cross-referencing the existing literature. Molecular and biological pathways that are significantly enriched were evaluated using gene ontology. A total of 184 IRD-causing genes were evaluated. Of these, 31 (16.8%) genes exhibited RAE. LOFI was exhibited in 6/31 (19.4%) of the RAE genes and 18/153 (11.8%) of the BAE genes. Brain tissue exhibited BAE in 107/128 (83.6%) genes for both sexes. The molecular pathways significantly enriched among BAE genes were photoreceptor activity, tubulin binding, and nucleotide/ribonucleotide binding. The biologic pathways significantly enriched for RAE genes were equilibrioception, parallel actin filament bundle assembly, photoreceptor cell outer segment organization, and protein depalmitoylation. Allele-specific expression may be a mechanism underlying IRD phenotypic variability, with clonal populations of embryologic precursor cells exhibiting RAE. Brain tissue preferentially exhibited BAE, possibly due to selective pressures against RAE. Pathways critical for cellular and visual function were enriched in BAE, which may offer a survival benefit.

Hypomorphic variants in inherited retinal and ocular diseases: A review of the literature with clinical cases.

Hypomorphic variants decrease, but do not eliminate, gene function via a reduction in the amount of mRNA or protein product produced by a gene or by production of a gene product with reduced function. Many hypomorphic variants have been implicated in inherited retinal diseases (IRDs) and other genetic ocular conditions; however, there is heterogeneity in the use of the term "hypomorphic" in the scientific literature. We searched for all hypomorphic variants reported to cause IRDs and ocular disorders. We also discuss the presence of hypomorphic variants in the patient population of our ocular genetics department over the past decade. We propose that standardized criteria should be adopted for use of the term "hypomorphic" to describe gene variants to improve genetic counseling and patient care outcomes.

Incarceration history is associated with HIV infection among community-recruited people who inject drugs in Europe: A propensity-score matched analysis of cross-sectional studies.

AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.

A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses.

Introduction: Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM. Methods: We developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-ß) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNß-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNß-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective. Results: 12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses. Discussion: Our study found that VSV-IFNß -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNß-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.