Rotational Thromboelastometry as a Diagnostic Tool for Persistent Infection in Two-Stage Exchange Arthroplasty.

Background/Objectives: There is a lack of reliable biomarkers for diagnosis of infection eradication prior to second-stage reimplantation in two-stage exchange arthroplasty for periprosthetic joint infections (PJIs). The aim of this study was to assess the diagnostic accuracy of rotational thromboelastometry (ROTEM) for persistent infection in two-stage exchange arthroplasties. Methods: A pilot, retrospective analysis was performed including 70 patients who underwent a two-stage exchange arthroplasty for PJI. They were categorized as patients without (n = 64) or patients with persistent infection (n = 6) prior to reimplantation. Definition of persistent infection prior to reimplantation was based on the 2018 ICM criteria. Conventional coagulation biomarkers and ROTEM parameters were compared between groups. Results: Higher FIBTEM MCF values were associated with persistent infection (odds ratio [OR], 1.30, 95% confidence interval [CI], 1.04-1.63; p = 0.020), and FIBTEM MCF had the highest diagnostic accuracy for persistent infection prior to second-stage reimplantation (AUC, 0.907; 95% CI, 0.812-1.000). A cut-off value ≥ 18 mm for FIBTEM MCF was found to have 100.0% sensitivity and 73.4% specificity for diagnosing persistent infection prior to second-stage reimplantation. Moreover, the diagnostic accuracy of FIBTEM MCF was higher than that of fibrinogen levels (p = 0.036) and D-dimer (p = 0.006). Conclusions: Our findings indicate that ROTEM parameters have the potential to identify persistent infections before reimplantation in two-stage exchange arthroplasties for PJI. Such coagulation biomarkers could provide guidance regarding the optimal timing for reimplantation. Further studies in larger populations are warranted to validate the diagnostic accuracy of ROTEM parameters for persistent PJI.

Molecular epidemiology of HIV among people who inject drugs after the HIV-outbreak in Athens, Greece: Evidence for a 'slow burn' outbreak.

BACKGROUND: New diagnoses of HIV-1 infection among people who inject drugs (PWID) in Athens, Greece, saw a significant increase in 2011 and a subsequent decline after 2013. Despite this, ongoing HIV-1 transmission persisted from 2014 to 2020 within this population. Our objective was to estimate the time of infection for PWID in Athens following the HIV-1 outbreak, explore the patterns of HIV-1 dispersal over time, and determine the duration from infection to diagnosis. METHODS: Time from HIV-1 infection to diagnosis was estimated for 844 individuals infected within 4 PWID-specific clusters and for 8 PWID infected with sub-subtype A6 diagnosed during 2010-2019. Phylogeny reconstruction was performed using the maximum-likelihood method. HIV-1 infection dates were based on molecular clock calculations. RESULTS: In total 86 of 92 (93.5%) sequences from PWID diagnosed during 2016-2019 were either related to the previously identified PWID-specific clusters (n = 81) or belonged to a new A6 cluster (n = 5). The median time between infection and diagnosis was 0.42 years during the outbreak period and 0.70 years during 2016-2019 (p < 0.001). The proportion of clustered sequences from PWID was very low at 5.3% during the pre-outbreak period (1998-2009), saw an increase to 41.7% one year before the outbreak in 2010, and consistently remained high during the whole period after 2011, spanning the post-outbreak period (2016-2019) with a range from 92.9% to 100%. CONCLUSIONS: The substantial proportion of clustered infections (93.5%) during 2016-2019 implies a persistent 'slow burn' HIV outbreak among PWID in Athens, suggesting that the outbreak was not successfully eliminated. The consistently high proportion of clustered sequences since the onset of the outbreak suggests the persistence of ongoing HIV-1 transmission attributed to injection practices. Our findings underscore the importance of targeted interventions among PWID, considering the ongoing transmission rate and prolonged time from infection to diagnosis.

Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability.

BACKGROUND: Plexins are large transmembrane receptors for the semaphorin family of signalling proteins. Semaphorin-plexin signalling controls cellular interactions that are critical during development as well as in adult life stages. Nine plexin genes have been identified in humans, but despite the apparent importance of plexins in development, only biallelic PLXND1 and PLXNA1 variants have so far been associated with Mendelian genetic disease. METHODS: Eight individuals from six families presented with a recessively inherited variable clinical condition, with core features of amelogenesis imperfecta (AI) and sensorineural hearing loss (SNHL), with variable intellectual disability. Probands were investigated by exome or genome sequencing. Common variants and those unlikely to affect function were excluded. Variants consistent with autosomal recessive inheritance were prioritised. Variant segregation analysis was performed by Sanger sequencing. RNA expression analysis was conducted in C57Bl6 mice. RESULTS: Rare biallelic pathogenic variants in plexin B2 (PLXNB2), a large transmembrane semaphorin receptor protein, were found to segregate with disease in all six families. The variants identified include missense, nonsense, splicing changes and a multiexon deletion. Plxnb2 expression was detected in differentiating ameloblasts. CONCLUSION: We identify rare biallelic pathogenic variants in PLXNB2 as a cause of a new autosomal recessive, phenotypically diverse syndrome with AI and SNHL as core features. Intellectual disability, ocular disease, ear developmental abnormalities and lymphoedema were also present in multiple cases. The variable syndromic human phenotype overlaps with that seen in Plxnb2 knockout mice, and, together with the rarity of human PLXNB2 variants, may explain why pathogenic variants in PLXNB2 have not been reported previously.

Racial Disparities in Infliximab Efficacy for Ulcerative Colitis: Evidence Synthesis and Effect Modification Assessment.

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods to generate race-specific efficacy estimates. Then, we tested the effect modification by race by comparing the race-specific estimates derived from independent evidence syntheses. We computed ratios of relative risks (RRRs) and performed tests of statistical interaction. We analyzed data from five randomized, placebo-controlled trials evaluating IFX as induction and maintenance therapy for adults with moderate-to-severe UC (875 participants; 45% Asians). We found no substantial evidence of racial differences concerning the efficacy of IFX in inducing clinical response (RRR = 0.89, 95% CI: 0.66-1.20; p = 0.44), clinical remission (RRR = 0.58, 95% CI: 0.24-1.44; p = 0.24), and mucosal healing (RRR = 0.99, 95% CI: 0.69-1.41; p = 0.95), or maintaining clinical remission (RRR = 0.81, 95% CI: 0.46-1.42; p = 0.45) and mucosal healing (RRR = 0.84, 95% CI: 0.48-1.46; p = 0.53), between Asian and Caucasian populations. Future clinical studies should expand the participation of racial minorities to comprehensively assess potential racial differences in the effectiveness of advanced therapies, including IFX, in the context of treating UC.

Heterozygous COL17A1 variants are a frequent cause of amelogenesis imperfecta.

BACKGROUND: Collagen XVII is most typically associated with human disease when biallelic COL17A1 variants (>230) cause junctional epidermolysis bullosa (JEB), a rare, genetically heterogeneous, mucocutaneous blistering disease with amelogenesis imperfecta (AI), a developmental enamel defect. Despite recognition that heterozygous carriers in JEB families can have AI, and that heterozygous COL17A1 variants also cause dominant corneal epithelial recurrent erosion dystrophy (ERED), the importance of heterozygous COL17A1 variants causing dominant non-syndromic AI is not widely recognised. METHODS: Probands from an AI cohort were screened by single molecule molecular inversion probes or targeted hybridisation capture (both a custom panel and whole exome sequencing) for COL17A1 variants. Patient phenotypes were assessed by clinical examination and analyses of affected teeth. RESULTS: Nineteen unrelated probands with isolated AI (no co-segregating features) had 17 heterozygous, potentially pathogenic COL17A1 variants, including missense, premature termination codons, frameshift and splice site variants in both the endo-domains and the ecto-domains of the protein. The AI phenotype was consistent with enamel of near normal thickness and variable focal hypoplasia with surface irregularities including pitting. CONCLUSION: These results indicate that COL17A1 variants are a frequent cause of dominantly inherited non-syndromic AI. Comparison of variants implicated in AI and JEB identifies similarities in type and distribution, with five identified in both conditions, one of which may also cause ERED. Increased availability of genetic testing means that more individuals will receive reports of heterozygous COL17A1 variants. We propose that patients with isolated AI or ERED, due to COL17A1 variants, should be considered as potential carriers for JEB and counselled accordingly, reflecting the importance of multidisciplinary care.

Factors Associated with Extended-Spectrum ß-Lactamases and Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections: A Five-Year Retrospective Study.

Klebsiella pneumoniae is one of the leading causes of nosocomial infections. It has been estimated that nosocomial infection by Klebsiella pneumoniae comprises 3-8% of all nosocomial infections. Klebsiella pneumoniae bloodstream infections (BSIs) occur worldwide with varying mortality. Resistant strains, like those producing extended-spectrum beta-lactamases (ESBL) and carbapenemases, are becoming increasingly common, especially in hospital settings, posing therapeutic challenges. In this article, we aimed to study the epidemiology and risk factors of BSIs due to resistant Klebsiella pneumoniae strains in the period 1 January 2014-31 December 2018 at the Nicosia General Hospital, the largest tertiary hospital in Cyprus. Data on demographics, co-morbidities, prior hospitalization, prior intensive care unit (ICU) admission, previous antimicrobial use, nosocomial acquisition of the infection, the presence of a prosthetic device or surgery, and the primary site of infection were retrospectively recorded. Associations between the detection of ESBL Klebsiella pneumoniae BSIs and factors/covariates were examined using logistic regression. This study involved 175 patients with BSI caused by Klebsiella pneumoniae. Of these, 61 BSIs were caused by ESBL strains, 101 by non-ESBL, and 13 by carbapenem-resistant (CR) strains. In univariable analyses, age, sex, heart disease, antimicrobial use during current admission, previous hospitalization (ward or ICU), and primary BSI were associated with the presence of an ESBL strain. Antibiotic use during current admission and heart disease remained statistically significantly associated with ESBL Klebsiella pneumoniae BSI in multivariable models. Antibiotic use during current admission, respiratory infection, and a recent history of surgery were more prevalent among CR Klebsiella pneumoniae BSI patients than among non-CR Klebsiella pneumoniae BSI patients. Our study showed that recent antimicrobial use and heart disease were associated with BSI due to ESBL-producing Klebsiella pneumoniae. This finding could inform clinical practice in hospital settings.

A Pilot Observational Study Evaluating the Diagnostic Capacity of Rotational Thromboelastometry in Periprosthetic Joint Infections.

BACKGROUND: Periprosthetic joint infections (PJIs) are associated with altered hemostatic dynamics; therefore, coagulation laboratory methods such as rotational thromboelastometry (ROTEM) may be valuable in their diagnosis. The aim of this study was to evaluate the diagnostic role of ROTEM in PJI. METHODS: A diagnostic study was conducted including 65 patients who underwent revision total hip arthroplasty or total knee arthroplasty due to PJI (30 patients) or aseptic loosening (35 patients). Preoperative laboratory evaluation included conventional coagulation studies, inflammatory markers, and ROTEM analysis. These parameters were compared between patients with PJI and patients with aseptic loosening. RESULTS: Several ROTEM parameters differed in the patients with PJI, indicating a higher coagulation potential associated with PJI. Specifically, the development of PJI was associated with higher EXTEM maximum clot firmness (MCF) (odds ratio [OR], 1.12 [95% confidence interval (CI), 1.04 to 1.20]; p = 0.001). Among the ROTEM parameters, EXTEM MCF was found to have the highest diagnostic accuracy for PJI (area under the receiver operating characteristic curve, 0.850; sensitivity, 76.6%; specificity, 91.4%), which was comparable with C-reactive protein (CRP) (p = 0.22) and erythrocyte sedimentation rate (ESR) (p = 0.65), but higher than D-dimer (p = 0.037). Moreover, the combined diagnostic accuracy of elevated EXTEM MCF and CRP was improved compared with CRP alone (p = 0.019). CONCLUSIONS: Our results indicate that ROTEM analysis might be helpful for the detection of the hemostatic derangements that are associated with the development of PJI. However, because of the small size of this pilot study, further research is needed to investigate the value of incorporating viscoelastic studies in diagnostic scores for PJI. LEVEL OF EVIDENCE: Diagnostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Ambient climatic factors and term birthweight: A study of critical windows of exposure in the Republic of Cyprus.

BACKGROUND: Reduced birthweight is associated with adverse perinatal and long-term outcomes. A few studies examined the association between climatic factors and birthweight with inconsistent results probably due to differences in exposure assessment, statistical models, climatic parameters, and study populations. METHODS: We obtained data from the Republic of Cyprus birth registry from 2007 to 2020, and matched climatic exposures (i.e., temperature, relative humidity, temperature variability, humidity variability) by the hospital district at birth. We used distributed lag models to examine the association between term birthweight, temperature, humidity, and their variability to identify critical windows. Our models were adjusted for coarse particulate matter level (≤10 µm [PM10), and individual-level covariates. Subgroup analysis was conducted to examine effect modification by maternal age and education. RESULTS: We identified two critical windows of exposure to ambient temperature at early and late pregnancy. The cumulative change of birthweight per 5 °C increases in mean weekly temperature was -57.27 (2%) (95% Confidence Interval [CI]: 99.62 (3.1%), -14.92 (0.5%)) and -79.2 (2.5%) (95%CI: 117.03 (3.5%), -41.52 (1.3%)) grams during weeks 1-8 and weeks 28-37, respectively. There was no significant effect of humidity, temperature variability, or humidity variability on birthweight. Based on subgroup analysis, mothers with post-secondary education were more sensitive to temperature, but the marginal significance of differences in effect estimates may be linked with differences in sample size. CONCLUSION: Our study suggests that higher ambient temperature exposure during early and late pregnancy is associated with lower birthweight in main and subgroup analysis. The findings demonstrate in a country highly impacted by climate change like Cyprus that rising temperatures may be associated with perinatal outcomes in susceptible populations during sensitive windows of exposure.

A novel artificial neural network methodology to produce high-resolution bioclimatic maps using Earth Observation data: A case study for Cyprus.

The aim of this research is to propose a novel methodology that exploits Earth Observation (EO) data to accurately produce high-resolution bioclimatic maps at large spatiotemporal scales. This method directly links EO products (i.e., land surface temperature - LST and Normalized Difference Vegetation Index - NDVI) to air temperature (Tair) and such thermal indices as the Universal Thermal Climate Index (UTCI), and the Physiologically Equivalent Temperature (PET) to produce large-scale high-quality bioclimatic maps at a spatial resolution of 100 m. The proposed methodology is based on Artificial Neural Networks (ANNs), and the bioclimatic maps are developed with the use of Geographical Information Systems. High-resolution LST maps are produced from the spatial downscaling of EO images and the application of the methodology in the case of the island of Cyprus highlights the ability of EO parameters to estimate accurately Tair as well as the above mentioned thermal indices. The results are validated for different conditions and the overall Mean Absolute Error for each case ranges from 1.9 °C for Tair to 2.8 °C for PET and UTCI. The trained ANNs could be used in near real-time for estimating the spatial distribution of outdoor thermal conditions and for assessing the relationship between human health and the outdoor thermal environment. On the basis of the developed bioclimatic maps, high-risk areas were identified. Furthermore, the study examines the relationship between land cover and Tair, UTCI, and PET, and the results provide evidence of the suitability of the method to monitor the dynamics of the urban environment and the effectiveness of urban nature-based solutions. Studies on bioclimate analysis monitor thermal environment, raise awareness and enhance the capacity of national public health systems to respond to thermally-induced health risks.

Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines.

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.

Methods for Assessing Spillover in Network-Based Studies of HIV/AIDS Prevention among People Who Use Drugs.

Human Immunodeficiency Virus (HIV) interventions among people who use drugs (PWUD) often have spillover, also known as interference or dissemination, which occurs when one participant's exposure affects another participant's outcome. PWUD are often members of networks defined by social, sexual, and drug-use partnerships and their receipt of interventions can affect other members in their network. For example, HIV interventions with possible spillover include educational training about HIV risk reduction, pre-exposure prophylaxis, or treatment as prevention. In turn, intervention effects frequently depend on the network structure, and intervention coverage levels and spillover can occur even if not measured in a study, possibly resulting in an underestimation of intervention effects. Recent methodological approaches were developed to assess spillover in the context of network-based studies. This tutorial provides an overview of different study designs for network-based studies and related methodological approaches for assessing spillover in each design. We also provide an overview of other important methodological issues in network studies, including causal influence in networks and missing data. Finally, we highlight applications of different designs and methods from studies of PWUD and conclude with an illustrative example from the Transmission Reduction Intervention Project (TRIP) in Athens, Greece.

Fibrinolysis shutdown and elevated D-dimer levels have high prognostic capacity for postoperative thromboembolic complications in patients with bone tumors.

Surgical resection of malignant bone tumors is associated with a high risk of venous thromboembolism (VTE). The purpose of this study was to evaluate the association between rotational thromboelastometry (ROTEM) parameters and VTE following oncologic resections, and to evaluate their prognostic capacity for this complication. A prospective observational study was conducted including 113 patients who underwent surgical resection of malignant bone tumors. ROTEM analysis and conventional coagulation studies were performed preoperatively and on the 2nd postoperative day, while patients were followed for the development of VTE. Logistic regression was used to assess the association between ROTEM parameters and occurrence of VTE. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were calculated as measures of discrimination and predictive accuracy. Fourteen patients (12.4%) developed symptomatic VTE. Development of VTE was associated with shortened INTEM CFT (Odds Ratio [OR] 0.90, 95% Confidence Interval [CI] 0.84 - 0.96, p = 0.004), higher INTEM A10 (OR 1.21, 95% CI 1.07 - 1.36, p = 0.002), higher INTEM MCF (OR 1.22, 95% CI 1.08 - 1.37, p = 0.001) and higher INTEM LI60 (OR 2.10, 95% CI 1.38 - 3.21, p = 0.001). An INTEM LI60 value indicative of fibrinolysis shutdown (≥ 98%) had the best predictive accuracy for VTE (AUC = 0.887, 95% CI 0.824 - 0.951, sensitivity = 100%, specificity = 67.0%), higher than that of D-dimer levels (p = 0.028). ROTEM parameters were promising predictors of symptomatic VTE. Fibrinolysis shutdown as reflected by ROTEM LI60 and high D-dimer levels can aid the identification of high-risk patients. Future studies should evaluate whether the addition of ROTEM findings to an expanded risk-assessing model can improve the predictive capacity and provide better guidance in thromboprophylaxis.

Finding influential subjects in a network using a causal framework.

Researchers across a wide array of disciplines are interested in finding the most influential subjects in a network. In a network setting, intervention effects and health outcomes can spill over from one node to another through network ties, and influential subjects are expected to have a greater impact than others. For this reason, network research in public health has attempted to maximize health and behavioral changes by intervening on a subset of influential subjects. Although influence is often defined only implicitly in most of the literature, the operative notion of influence is inherently causal in many cases: influential subjects are those we should intervene on to achieve the greatest overall effect across the entire network. In this work, we define a causal notion of influence using potential outcomes. We review existing influence measures, such as node centrality, that largely rely on the particular features of the network structure and/or on certain diffusion models that predict the pattern of information or diseases spreads through network ties. We provide simulation studies to demonstrate when popular centrality measures can agree with our causal measure of influence. As an illustrative example, we apply several popular centrality measures to the HIV risk network in the Transmission Reduction Intervention Project and demonstrate the assumptions under which each centrality can represent the causal influence of each participant in the study.

Experimental Boson Sampling Enabling Cryptographic One-Way Function.

Boson sampling is a computational problem, which is commonly believed to be a representative paradigm for attaining the milestone of quantum advantage. So far, massive efforts have been made to the experimental large-scale boson sampling for demonstrating this milestone, while further applications of the machines remain a largely unexplored area. Here, we investigate experimentally the efficiency and security of a cryptographic one-way function that relies on coarse-grained boson sampling, in the framework of a photonic boson-sampling machine fabricated by a femtosecond laser direct writing technique. Our findings demonstrate that the implementation of the function requires moderate sample sizes, which can be over 4 orders of magnitude smaller than the ones predicted by the Chernoff bound; whereas for numbers of photons n≥3 and bins d∼poly(m,n), the same output of the function cannot be generated by nonboson samplers. Our Letter is the first experimental study that deals with the potential applications of boson sampling in the field of cryptography and paves the way toward additional studies in this direction.

Risk Factors, Diagnosis, and Treatment of Neonatal Fungal Liver Abscess: A Systematic Review of the Literature.

(1) Background: Although invasive fungal infections are a major cause of neonatal morbidity and mortality, data on the incidence and outcomes of localized abscesses in solid organs due to fungal infections are scarce. The aim of this study was to consolidate evidence and enhance our understanding on neonatal liver abscesses due to invasive fungal infections. (2) Methods: An electronic search of the PubMed and Scopus databases was conducted, considering studies that evaluated fungal liver abscesses in the neonatal population. Data on the epidemiology, clinical course, treatment, and outcome of these infections were integrated in our study. (3) Results: Overall, 10 studies were included presenting data on 19 cases of neonatal fungal liver abscesses. Candida spp. were the most common causative pathogens (94.7%). Premature neonates constituted the majority of cases (93%), while umbilical venous catheter placement, broad spectrum antibiotics, and prolonged parenteral nutrition administration were identified as other common predisposing factors. Diagnosis was established primarily by abdominal ultrasonography. Medical therapy with antifungal agents was the mainstay of treatment, with Amphotericin B being the most common agent (47%). Abscess drainage was required in four cases (21%). Eradication of the infection was achieved in the majority of cases (80%). (4) Conclusions: Even though fungal liver abscess is a rare entity in the neonatal population, clinicians should keep it in mind in small, premature infants who fail to respond to conventional treatment for sepsis, particularly if an indwelling catheter is in situ. A high index of suspicion is necessary in order to achieve a timely diagnosis and the initiation of the appropriate treatment.

Pilot Testing Two Versions of a Social Network Intervention to Increase HIV Testing and Case-finding among Men in South Africa's Generalized HIV Epidemic.

Locating undiagnosed HIV infections is important for limiting transmission. However, there is limited evidence about how best to do so. In South Africa, men have been particularly challenging to reach for HIV testing due, in part, to stigma. We pilot-tested two versions of a network-based case-finding and care-linkage intervention. The first, TRIP, asked "seeds" (original participants) to recruit their sexual and/or injection partners. The second, TRIPLE, aimed to circumvent some stigma-related issues by asking seeds to recruit anyone they know who might be at risk of being HIV-positive-unaware. We recruited 11 (18% male) newly diagnosed HIV-positive (NDP) seeds from two clinics in KwaZulu-Natal, South Africa and randomly assigned them to either TRIP or TRIPLE. Network members were recruited two steps from each seed. The TRIP arm recruited 12 network members; the TRIPLE arm recruited 62. Both arms recruited NDPs at higher rates than local clinic testing, with TRIP (50.0%) outperforming (p = 0.012) TRIPLE (14.5%). However, TRIPLE (53.2%) was far superior to clinics (27.8%) and to TRIP (25.0%) at recruiting men. Given challenges around testing and treating men for HIV in this context, these findings suggest that the TRIPLE expanded network-tracing approach should be tested formally among larger samples in multiple settings.

Estimating Causal Effects of HIV Prevention Interventions with Interference in Network-based Studies among People Who Inject Drugs.

Evaluating causal effects in the presence of interference is challenging in network-based studies of hard-to-reach populations. Like many such populations, people who inject drugs (PWID) are embedded in social networks and often exert influence on others in their network. In our setting, the study design is observational with a non-randomized network-based HIV prevention intervention. Information is available on each participant and their connections that confer possible HIV risk through injection and sexual behaviors. We considered two inverse probability weighted (IPW) estimators to quantify the population-level spillover effects of non-randomized interventions on subsequent health outcomes. We demonstrated that these two IPW estimators are consistent, asymptotically normal, and derived a closed-form estimator for the asymptotic variance, while allowing for overlapping interference sets (groups of individuals in which the interference is assumed possible). A simulation study was conducted to evaluate the finite-sample performance of the estimators. We analyzed data from the Transmission Reduction Intervention Project, which ascertained a network of PWID and their contacts in Athens, Greece, from 2013 to 2015. We evaluated the effects of community alerts on subsequent HIV risk behavior in this observed network, where the connections or links between participants were defined by using substances or having unprotected sex together. In the study, community alerts were distributed to inform people of recent HIV infections among individuals in close proximity in the observed network. The estimates of the risk differences for spillover using either IPW estimator demonstrated a protective effect. The results suggest that HIV risk behavior could be mitigated by exposure to a community alert when an increased risk of HIV is detected in the network.

Effect of Vaccination against SARS-CoV-2 on Long COVID-19: A Narrative Review.

Vaccines against SARS-CoV-2 have saved millions of lives and played an important role in containing the COVID-19 pandemic. Vaccination against SARS-CoV-2 is also associated with reduced disease severity and, perhaps, with COVID-19 symptom burden. In this narrative review, we present, in a clinically relevant question-and-answer manner, the evidence regarding the association between vaccination against SARS-CoV-2 and long COVID-19. We discuss how the mechanism of action of vaccines could interplay with the pathophysiology of post-COVID-19 condition. Furthermore, we describe how specific factors, such as the number of vaccine doses and the type of SARS-CoV-2 variants, may affect post-COVID-19 condition. We also discuss the role of timing for vaccination in relation to the onset of long COVID-19 symptoms, as it seems to affect the frequency and severity of the condition. Additionally, we describe the potential modifying effect of age, as well as the association of type and level of immune response with long COVID-19. We also describe how system-specific long COVID-19 sequelae, namely neurocognitive-psychologic symptoms and cardiovascular pathology, could be altered by vaccination. Last, we address the question of whether seasonal influenza vaccination has a meaningful impact on the frequency of long COVID-19.

Recent HIV Infection: Diagnosis and Public Health Implications.

The early period of infection with human immunodeficiency virus (HIV) has been associated with higher infectiousness and, consequently, with more transmission events. Over the last 30 years, assays have been developed that can detect viral and immune biomarkers during the first months of HIV infection. Some of them depend on the functional properties of antibodies including their changing titers or the increasing strength of binding with antigens over time. There have been efforts to estimate HIV incidence using antibody-based assays that detect recent HIV infection along with other laboratory and clinical information. Moreover, some interventions are based on the identification of people who were recently infected by HIV. This review summarizes the evolution of efforts to develop assays for the detection of recent HIV infection and to use these assays for the cross-sectional estimation of HIV incidence or for prevention purposes.

Allergy-Test-Based Elimination Diets for the Treatment of Eosinophilic Esophagitis: A Systematic Review of Their Efficacy.

Eosinophilic esophagitis (EoE) is an immune-mediated esophageal disorder, linked with sensitization to food and airborne allergens. Dietary manipulations are proposed for the management of EoE inflammation and are often successful, confirming the etiological role of food allergens. Three different dietary approaches are widely used: the elemental, the empirical, and the allergy-test-driven approach. We performed a systematic review to assess the evidence on the association of allergens, detected by allergy tests, with clinically confirmed triggers of EoE. We systematically searched PubMed, Scopus, Embase, and the Cochrane Library, through 1 June 2021. We sought studies examining the correlation of skin-prick tests (SPT), atopy patch tests (APT), specific IgE, and serum-specific IgG4, with confirmed triggers of EoE. Data on the use of prick-prick tests were also extracted. Evidence was independently screened by two authors against predefined eligibility criteria. Risk of bias was assessed with the ROBINS-I tool. Of 52 potentially eligible studies, 16 studies fulfilling quality criteria were included. These studies used one to three different allergy tests detecting food sensitization. The positive predictive value was generally low to moderate but higher when a combination of tests was used than single-test evaluations. None of the selected studies used serum-specific IgG4. Although an extreme methodological variability was noticed in the studies, allergy-based elimination diets were estimated to be efficient in 66.7% of the cases. The efficacy of targeted elimination diets, guided by SPT, sIgE, and/or APT allergy tests, does not appear superior to empirical ones. In the future, tests using esophageal prick testing or ex vivo food antigen stimulation may prove more efficient to guide elimination diets.