Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory systemic disease of unknown etiology that can affect one or multiple organs. The disease can mimic many infectious and inflammatory diseases, mainly causing organ enlargement or hyperplasia. Its diagnosis primarily relies on clinical, serologic, and histological features . Here, we report a rare case of IgG4-related periodontitis, and review the relevant literatures.A 38-year-old Chinese man visited the Department of Periodontics with gingival enlargement, loose teeth, and tooth loss. The patient had very poor oral hygiene and a large amount of calculus. Gingivae were edematous with deep periodontal pockets and attachment loss. Panoramic radiography showed alveolar bone loss. Serologic examination showed that IgG was 23.70 g/L and IgG4 concentration was 2.800 g/L. There was significant lymphoplasmacytic infiltration, a storiform pattern of fibrosis, and mitotic figures with hematoxylin and eosin staining; immunohistochemical staining showed 10 scattered IgG4-positive plasma cells in a high-power field. The patient was diagnosed as IgG4-related periodontitis. He received a course of corticosteroids with periodontal therapy, and the enlargement was significantly improved without recurrence.IgG4-RD in the oral and maxillofacial region mainly involves salivary glands, but this rare case was characterized by enlarged gingivae. The differential diagnosis of IgG4-RD should be based on the clinical features and serologic (IgG4) and histopathological examinations. Corticosteroid therapy is effective for most IgG4-RD patients. Taken together, we hope this case report and the literature review can help dentists to improve their understanding of the IgG4-RD.The online version contains supplementary material available at 10.1186/s12903-021-01592-2. Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory and systemic disease of unknown etiology that involves various organs, such as the pancreas, bile duct, orbital tissues, lacrimal and salivary glands, lungs, skin, liver, arteries, kidneys, retroperitoneum, prostate, gallbladder, and lymph nodes –4. IgG4-. The chief complaint of the patient was generalized gingival enlargement beginning 2 years ago, sometimes with pus. The teeth gradually loosened several months ago, and the left maxillary first molar was lost following severe pain. A local doctor diagnosed him as periodontitis, and then he was referred to the Department of Periodontics for periodontal therapy.A 38-year-old Chinese man visited the Department of Periodontics  with gingival enlargement, loose teeth, and tooth losso-IIIo, and was IIIo in the left maxillary first premolar and second premolar  demonstrated ulceration, a large infiltration of lymphoplasmacytic cells, a storiform pattern of fibrosis, and mitotic figures Fig. C-a, b; tThe treatment plan for this patient was oral corticosteroids and periodontal therapy guided by the Department of Rheumatology and Immunology  and the Department of Periodontics. The rheumatologist recommended oral corticosteroids therapy. The initial dose of prednisolone was 0.6 mg/kg for 2 weeks (40 mg/day), which was then tapered by 5 mg every week for 6 weeks to determine a maintenance dose (5 mg/day). At the same time, the periodontist carried out periodontal therapy, including oral hygiene instruction, supragingival cleaning, subgingival scaling, and root planning . In addition, the histological examination (H&E and IHC) showed marked lymphoplasmacytic infiltration and fibrosis, with scattered infiltration of 10 IgG4-positive plasma cells in the HPF, so the final diagnosis in this patient was IgG4-related periodontitis. Although there was no predominant venulitis, it is possible that due to the size and location of the lesions, restricted sampling obscured venulitis . Everds There are many reasons for gingival enlargement, such as dental plaque, drugs, autoimmune response, and genetic factors, as well as systemic diseases. Local and generalized gingival enlargement caused by IgG4-RDs is similar to plasma cell granuloma, drug-induced gingival enlargement, hereditary gingival fibromatosis, epulis, periodontitis, and leukemia Table . One stuIn the oral and maxillofacial regions, the occurrence of involved gingivae in IgG4-RDs  is relatively rare, and the most common diseases are MD and Kuttner’s tumor  . PatientWe performed a literature review through the PubMed database using the terms “IgG4-related,” “case,” “oral,” and “maxillofacial” , 35–49. Overall, the common chief complaints of patients are neck enlargement, dry mouth, enlargement of lymph nodes, gingival hyperplasia, and mucosal enlargement. The clinical manifestations in the oral and maxillofacial regions include enlargement and painless hard masses in the salivary glands, and the radiographs often show enlargement of the salivary glands. Even though some IgG4-RDs appear first in the oral cavity, the symptoms in other organs can’t be overlooked, since 7 previous cases demonstrated other organs involvement Table . Among 2Currently, there is no standard treatment plan for IgG4-RDs, but they are generally sensitive to corticosteroids therapy. The recommended dosage is prednisone 0.6 mg /kg/day for 2 to 4 weeks. After 3–6 months, it is gradually reduced to 5 mg/day, and then 2.5–5 mg/day for 3 years , 44, 48.This review reported a rare clinical case of IgG4-related periodontitis with generalized and severe gingival enlargement in the oral and maxillofacial region. As systemic diseases, IgG4-RDs have gradually gained the attention of medical community but the etiology and pathology of these diseases are still unclear. The clinical features of IgG4-RDs are diverse and non-specific, involving multiple organs, and diagnosis should be based on the clinical, serologic, and histological features (ratio of IgG4/IgG or number of plasma cells in HPF); otherwise, IgG4-RDs are easily misdiagnosed. In addition, an early and correct diagnosis is the main goal for the future studies. When we see abnormal edematous and hyperplastic gingivae that are different from the regular periodontal manifestations, serologic examinations should be performed first. If the serology is normal, we should consider biopsy and immunohistochemical staining of local tissues. The combination of serologic, histological, and clinical features can be a clue for further investigation. Of course, periodontitis as a rare manifestation of systemic disease is indeed confusing and difficult to diagnose.At present, several researchers are dedicated to developing more optimal, specific classification standards that can help to diagnose IgG4-RDs more quickly and accurately, but the relationship between IgG4-RDs and periodontitis still needs further investigation. Additionally, many oral symptoms may be associated with systemic diseases, so it is essential to pay attention to oral health. In conclusion, improvements are needed in correctly diagnosing and treating IgG4-RD, avoiding misdiagnosis, delivering timely treatment, alleviating symptoms, and improving prognosis.Additional file 1. Immunohistochemical staining was positive index for CD38 , Ki-67/mib-1, mum1, kappa , lambda , EBER , PCK . Additional file 2. Timeline of treatment


Further molecular studies are needed to be conducted to understand the mechanisms underlying the synergistic activity between Met and Ag+.Met enhanced the bactericidal effects of AgThe online version contains supplementary material available at 10.1186/s12866-021-02291-2. Enterococcus faecalis is one of the most frequently identified . Prts (19%) , manifests (19%) . DM mustts (19%) .Staphylococcus aureus and Pseudomonas aeruginosa, and possess an adjuvant antimicrobial effect when combined with other antibiotics [E. faecalis remains unknown.Poorly controlled glycemia was significantly associated with AP, while metformin hydrochloride (Met), a typical medicine for hypoglycemia treatment, was associated with a lower prevalence of AP . Recentlibiotics –20; howe+ is recognized as a broad-spectrum bactericidal metal ion widely used in medical applications; however, Ag+ has also been reported to cause discoloration, eye irritation, and allergic contact dermatitis [E. faecalis has been proven to develop resistance against Ag+, leading to the metal’s decreased antibacterial effectiveness [+ or nanoparticles has been used with other metal ions or chemicals to obtain a stronger synergistic antibacterial effect and lower cytotoxicity [+ against E. faecalis in diabetic environments, that is, high-glucose condition, remains unknown. In addition, whether there is a synergistic antibacterial effect against E. faecalis between Met and Ag+ under high-glucose conditions also remains unclear.Agrmatitis . E. faectiveness . To solvtoxicity –26. Desp+ against E. faecalis under normal or high-glucose conditions in vitro. It was hypothesized that Ag+ plus Met would show a synergistic inhibitory effect on planktonic E. faecalis and biofilm on dentin slices either in normal or high glucose conditions.Based on these concerns, this study aimed to investigate the synergistic antibacterial effect of Met and Ag3 with or without Met against E. faecalis in Brain Heart Infusion (BHI) broth with or without additional glucose were shown in Table 99 of Met was not detected at the tested concentrations. Under different concentrations of Met (3.2 and 6.4%), the MIC and MBC99 of AgNO3 decreased drastically.The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) results of Met and AgNO+ (40 μg/mL), Met (3.2 and 6.4%), and Ag++Met on planktonic E. faecalis in BHI or BHIG broth. 2% chlorhexidine (CHX) was used as a positive control in the CFU-counting test. The results of dynamic growth curves in Fig. ++Met group were significantly decreased (p < 0.0001) within 10 h. The CFU-counting tests  and increased antibacterial efficiencies -counting method were used to detect the antibacterial effects of Ag), Met 3. and 6.4%), Met 3. and 6.4%E. faecalis biofilm were cultured on human dentin slices, and their antibacterial effects were tested. The OD600 value measured within 10 h showed significantly decreased residual bacterial amount from the dentin slices in the Ag++Met and CHX groups  compared to the control group, even under the high glucose condition.Four-week + and Met was assessed on MC3T3-E1 cells in vitro. The results of the CCK-8 test  and an inhibitory effect on cell proliferation. Although the AM6.4 group showed a slight inhibitory effect, there was no significant difference when compared with the negative control group (p > 0.05). All other groups showed low cytotoxicity (p > 0.05).The cytotoxicity of Agest Fig.  showed t+ and Met on E. faecalis. MIC and MBC test, dynamic growth curve test and CFU-counting method were used to determine the synergistic antimicrobial effect on planktonic E. faecalis. The concentrations of metformin were selected based on the MIC test of metformin and pilot studies. The selected concentrations of 3.2 and 6.4% were 1/4 MIC and 1/2 MIC of metformin respectively, which could be better present the synergistic effect with silver ions than other concentrations as indicated in our pilot studies. According to the results, the combination of Ag+ (1/4 MIC) and Met (1/4 or 1/2 MIC) significantly inhibited the growth of planktonic E. faecalis in either normal or high glucose conditions. However, as previously reported, biofilm was more resistant to antimicrobial agents and harsh environments than planktonic bacteria [+ plus Met also showed strong synergistic inhibition effect on four-week E. faecalis biofilm on human dentin slices. Ag+ plus Met may be developed into a new effective and safe multifunctional antibacterial agent for root canal disinfection or other related medical areas under diabetic conditions.This study mainly focused on the synergistic inhibitory effect of Agbacteria . DespiteE. faecalis biofilm formation [E. faecalis into dentinal tubules was deeper [E. faecalis to bind to collagen and invade dentinal tubules [Previous studies have demonstrated that high glucose media can promote ormation , 29. Anos deeper . Local h tubules .E. faecalis has rarely been studied. In this study, MBC99 of Met was not detected at the tested concentrations, indicating the weak sterilization effect of Met on E. faecalis. In contrast, CHX, a biguanide compound, is widely used as an endodontic irrigant and medicament with confirmed activities against gram-positive and gram-negative bacteria, but showed lower cell viability compared to other irrigant in cytotoxicity tests [As a hypoglycemic medicine for the treatment of DM, Met has also been reported to be multifunctional as having anti-aging, anti-inflammation, anti-bacterial and anti-tumor properties –17, 19. ty tests , 33. Thety tests .+ is thought to be the interaction between Ag+ and the bacterial cell envelope, DNA, enzymes and proteins  inside the cell, as well as the production of reactive oxygen species [+ through various mechanisms such as the active efflux of ions from the cell [E. faecalis was also reported to be controlled by the energy derived from the catabolism of glucose and the proton concentration of the medium [+ in high glucose environment could probably be influenced by the sufficient glucose as an energy source for the efflux system. Met disrupt the bacterial cytoplasmic membrane and undermine the function of the PMF-driven efflux pump, therefore to promote the intracellular accumulation of doxycycline and restore tetracyclines susceptibility to multidrug-resistant bacteria [+ by increasing the permeability of the cell membrane and undermining the functions of the efflux pump, upon which the antibacterial effect of Ag+ was strengthened when acted together with Met.The molecular mechanism behind the antibacterial activity of Ag species , 36. Desthe cell . The inte medium . Proton e medium . The antbacteria . Met couE. faecalis, or indirectly mediated by the host response [E. faecalis, and lipoteichoic acids was reported to induce NLRP3 inflammasome expression by activating the nuclear factor-kappa B (NF-κB) signaling pathway [+.Damage in the periapical tissues can be caused directly by virulence factors and production (such as lipoteichoic acids and extracellular superoxide production) of response , 40. The pathway . DM show pathway . Metform pathway . In addi pathway , 44. Des++Met synergism showed strong antibacterial activity against both planktonic and biofilm E. faecalis in either normal or high-glucose conditions with low cytotoxicity.In conclusion, AgE. faecalis ATCC 29212  was used in this study and stored at −80 °C with 50% glycerol. For all experiments, bacteria were grown in Brain Heart Infusion  at 37 °C in an anaerobic incubator with 5% CO2 and 1% O2, and the E. faecalis bacterial density was standardized to the OD value of 1.0, using a spectrophotometer  at a wavelength of 600 nm, corresponding to a cell density of 109 CFU/mL. The standard bacterial suspension was used in subsequent experiments. BHIG broth was prepared by adding 25 mM glucose to the BHI broth.All procedures in this study were performed in accordance with relevant guidelines. 3 and Met was determined using the microdilution method as previously described [3 or Met were prepared with sterile distilled water, and 100 μL of the test solution was added to a 96-well microtiter plate. Another 100 μL E. faecalis bacterial suspension (106 CFU/mL) diluted in double-concentrated BHI or BHIG broth was transferred into each well. For AgNO3 or Met alone, the final concentrations ranged from 5 to 640 μg/mL or from 0.1 to 12.8%, respectively. For the AgNO3 + Met test, the concentration of Met remained unchanged (3.2% or 6.4%) with AgNO3 ranging from 5 to 640 μg/mL. the plates were incubated for 24 h at 37 °C in an anaerobic incubator with 5% CO2 and 1% O2 in the dark. A micro-plate reader  was used at 600 nm to evaluate cell growth. Each assay contained both experimental and negative controls (media only). The MIC was defined as the lowest concentration that inhibited E. faecalis growth after incubation, showing OD600 values closest to hose of the negative controls. For MBC experiments, 100 μL of solutions from wells without turbidity were cultured on BHI agar. At least three wells  were tested. MBC99 was determined to be the concentration with at least 99% inhibition. The measurements were performed in triplicate.The MIC for AgNOescribed . Briefly+ and Met solutions was identified according to previous studies [E. faecalis suspension was adjusted to 108 CFU/mL and incubated with AgNO3 solutions (40 μg/mL), Met solutions (3.2% or 6.4%) or their combinations in BHI and BHIG broth at 37 °C in an anaerobic incubator with 5% CO2 and 1% O2 in the dark. Aliquots were retrieved and optical density was measured at 600 nm every 2 h. The negative control was defined as the untreated E. faecalis. Each test was repeated six times.The antimicrobial effect identified of Ag studies . Briefly+ and Met. Briefly, 1 mL suspension (104 CFU/mL) of E. faecalis was incubated with different concentrations of AgNO3 and Met in BHI and BHIG broth for 24 h at 37 °C in an anaerobic incubator with 5% CO2 and 1% O2 in the dark. 2% CHX was used as a positive control because of its confirmed bactericidal effectiveness. After serial 10-fold dilution or no, 10 μL of bacterial sample from each group was retrieved and inoculated on BHI agar plates for a further 24 h. the CFU of E. faecalis was counted to evaluate the number of viable bacteria. The test was repeated six times for each group.The CFU counting method  was usedE. faecalis was calculated as:According to the results of the CFU counting test, the antibacterial efficiency (%) against Extracted third molar teeth were collected under the approval (2017–11) of the Ethics Committee of the School and Hospital of Stomatology, Wuhan University and cut into dentin slices with a size of 4 mm (width) × 4 mm (length) × 1 mm (thickness). All slices were thoroughly cleaned by ultrasound using distilled water, 5.25% sodium hypochlorite and 17% ethylenediaminetetraacetic acid in sequence for 4 min each, with distilled water for 1 min as the final wash. Finally, they were autoclaved at 121 °C in distilled water for 20 min , 46.E. faecalis suspension (108CFU/mL) in BHI or BHIG broth at 37 °C in an anaerobic incubator with 5% CO2 and 1% O2 for four weeks [3, Met, AgNO3-Met, and CHX gels for 7 days at 37 °C. Gels were prepared by mixing 0.15 g methylcellulose  with 2 mL of tested solutions. After 7 days, the slices were gently washed with PBS for three times and then soaked in 2 mL of fresh BHI or BHIG broth. Biofilm cells were dispersed by vortex mixing for 1 min. During 10 h of incubation, 200 μL suspension was retrieved for absorbance measurement at 600 nm every 2 h. Dentin slices without medication (methylcellulose gel only) were set as the negative control, while the group treated with 2%CHX gel was set as the positive control.For the antibacterial effect test, all dentin slices were evenly divided into two groups and soaked in 1 mL ur weeks , 48 Fres+ and Met on MC3T3-E1 subclone 14 osteoblastic cells (ATCC CRL-2594) in vitro was assessed using the cell counting kit-8  according to the previous studies [4 cells) were seeded into each well of a 96-well plate and cultured at 37 °C in a 5% CO2 atmosphere in α-minimum essential medium  with 10% fetal bovine serum (Hyclone) and 1% penicillin/streptomycin (Hyclone). The tested solutions were sterilized using a 0.22-μm filter . After incubation for 24 h, the culture medium was replaced with 200 μL of α-MEM and 10 μL of different dilutions containing AgNO3(40 μg/ mL), Met (3.2% or 6.4%) or their combinations and CHX (2%). After incubating for another 24 h, the supernatant was removed and the plate was washed with PBS. Finally, 100 μL of fresh α-MEM and 10 μL of CCK-8 were added and incubated in the dark for 1 h. The supernatant was transferred to a new 96-well plate, and the absorbance at 450 nm was measured using a microplate reader. The untreated group was used as the control. Wells containing only CCK-8 and α-MEM were used for background recordings (BKG). Each group included six repeated wells.The cytotoxicity of Ag studies . Two hunP < 0.05.All data are expressed as the mean ± S.E.M.. Data analysis was performed using the Graphpad Prism 8 . One-way analysis of variance (ANOVA) with a post hoc Dunnett t-test was performed for CFU and cytotoxicity assays. A two-way ANOVA was performed for the dynamic growth curve and biofilm assays. Statistical significance was set at Additional file 1: Table S1. Data of dynamic growth curve test were shown as mean OD600 and Standard Error of Means (SEM), which was plotted in Fig. Table S2. Data of colony-forming units (CFU)-counting test were shown as mean counting and SEM, which was plotted in Fig. Table S3. Data of biofilm test on dentin slices were shown as mean OD600 and SEM, which was plotted in Fig. Table S4. Data of cytotoxicity assays were shown as mean OD450 and SEM, which was plotted in Fig.


What is the most clinically beneficial and cost-effective antibiotic treatment strategy for injection drug use–associated infective endocarditis (IDU-IE)?Staphylococcus aureus was not a causative pathogen.In this decision analytical modeling study simulating 4 treatment strategies among 5 million individuals with IDU-IE in the US, a validated microsimulation model suggested that outpatient parenteral antimicrobial therapy was the most cost-effective strategy for the treatment of IDU-IE. A partial oral antibiotic treatment strategy was associated with the highest treatment completion rate and was most cost-effective when methicillin-resistant This study found that outpatient parenteral antimicrobial therapy and partial oral antibiotic therapy regimens were likely to be as clinically beneficial as and less costly than 6 weeks of inpatient intravenous antibiotic therapy for the treatment of IDU-IE. Emerging evidence supports the use of outpatient parenteral antimicrobial therapy (OPAT) and, in many cases, partial oral antibiotic therapy for the treatment of injection drug use–associated infective endocarditis (IDU-IE); however, long-term outcomes and cost-effectiveness remain unknown.To compare the added value of inpatient addiction care services and the cost-effectiveness and clinical outcomes of alternative antibiotic treatment strategies for patients with IDU-IE.This decision analytical modeling study used a validated microsimulation model to compare antibiotic treatment strategies for patients with IDU-IE. Model inputs were derived from clinical trials and observational cohort studies. The model included all patients with injection opioid drug use (N = 5 million) in the US who were eligible to receive OPAT either in the home or at a postacute care facility. Costs were annually discounted at 3%. Cost-effectiveness was evaluated from a health care sector perspective over a lifetime starting in 2020. Probabilistic sensitivity, scenario, and threshold analyses were performed to address uncertainty.The model simulated 4 treatment strategies: (1) 4 to 6 weeks of inpatient intravenous (IV) antibiotic therapy along with opioid detoxification , (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered medication for opioid use disorder , (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and (4) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy .Mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs).All modeled scenarios were initialized with 5 million individuals  who had a history of injection opioid drug use. The usual care strategy resulted in 18.63 LYs at a cost of $416 570 per person, with 77.6% of hospitalized patients completing treatment. Life expectancy was extended by each alternative strategy. The partial oral antibiotic strategy yielded the highest treatment completion rate (80.3%) compared with the OPAT strategy (78.8%) and the usual care/addiction care strategy (77.6%). The OPAT strategy was the least expensive at $412 150 per person. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. Increasing IDU-IE treatment uptake and decreasing treatment discontinuation made the partial oral antibiotic strategy more cost-effective compared with the OPAT strategy. When assuming that all patients with IDU-IE were eligible to receive partial oral antibiotic therapy, the strategy was cost-saving and resulted in 0.0247 additional discounted LYs. When treatment discontinuation was decreased from 3.30% to 2.65% per week, the partial oral antibiotic strategy was cost-effective compared with OPAT at the $100 000 per LY threshold.In this decision analytical modeling study, incorporation of OPAT or partial oral antibiotic approaches along with addiction care services for the treatment of patients with IDU-IE was associated with increases in the number of people completing treatment, decreases in mortality, and savings in cost compared with the usual care strategy of providing inpatient IV antibiotic therapy alone. This decision analytical modeling study assesses the added value of inpatient addiction care services and compares the cost-effectiveness and clinical outcomes of different antibiotic treatment strategies among 5 million individuals with injection drug use–associated infective endocarditis in the US. If current patterns continue, more than 250 000 individuals in the US may die of IDU-IE between 2020 and 2030.3 There is a substantial need to define optimal treatment strategies given the increasing burden of IDU-IE in the US.Hospitalizations associated with infective endocarditis in the US increased from 16 per 100 000 adults in 2003 to 22 per 100 000 adults in 2016.4 Emerging evidence exists for the use of oral antibiotic therapy for the treatment of many types of infective endocarditis and the use of outpatient parenteral antimicrobial therapy (OPAT) for at least part of the treatment course.9 However, patients with IDU-IE are often required to remain hospitalized until treatment completion.10 Almost 20% of patients admitted with IDU-IE have a patient-directed discharge .12 Alternative antibiotic treatment strategies that shorten hospitalization and allow patients to complete treatment elsewhere could increase the likelihood of treatment completion and decrease costs.Standard treatment for IDU-IE comprises 4 to 6 weeks of intravenous (IV) antibiotic therapy.Staphylococcus aureus infection but recommend that this approach only be used when parenteral antibiotic therapy is problematic.14 However, a retrospective cohort study5 found that people with IDU-IE who received a complete course of IV antibiotic therapy had similar readmission rates to those who could not complete inpatient IV antibiotic therapy and were provided partial oral antibiotic therapy at the time of patient-directed discharge.Current US treatment guidelines state that partial oral antibiotic therapy may be a reasonable option for patients with IDU-IE associated with uncomplicated right-sided 15 However, clinicians’ concerns regarding the misuse of a peripherally inserted central catheter to inject drugs in addition to treatment nonadherence, unstable living situations, and stigma associated with substance use have typically excluded people who inject drugs from receiving OPAT.17 Despite these concerns, a 2018 systematic review8 found that OPAT may be safe and beneficial for treating IDU-IE. To our knowledge, no study to date has compared the long-term impact and cost-effectiveness of OPAT with IV and partial oral antibiotic treatment strategies.Another strategy, OPAT, is widely used to treat infections that require prolonged antibiotic therapy, and this treatment strategy has a proven safety record.18 has highlighted the role of addiction care services in improving outcomes among individuals hospitalized with IDU-IE. Addiction care services, which can include addiction counseling, opioid withdrawal management, long-term medication titration, and referral and linkage to outpatient addiction care, have been reported to increase the likelihood of receiving medication for opioid use disorder (MOUD) during and after treatment for IDU-IE and have been associated with reductions in mortality risk19 and decreases in the probability of reinfection.21 Despite these benefits, an analysis from 1 hospital found that fewer than 8% of patients admitted with IDU-IE were discharged with any plans to start MOUD,22 reflective of a gap in treatment which has since been confirmed in broader studies.20Recent researchWe evaluated the likely long-term clinical outcomes and cost-effectiveness of different strategies for the treatment of IDU-IE. Given the emerging evidence and unanswered questions, we aimed to (1) compare the potential value of alternative antibiotic treatment strategies and (2) estimate the impact of addiction care services among patients with IDU-IE.CHEERS) reporting guideline for economic evaluations of health interventions  model used in the study and provided a waiver of informed consent because the study did not involve human participants. This study followed the Consolidated Health Economic Evaluation Reporting Standards  4 to 6 weeks of inpatient IV antibiotic therapy along with opioid detoxification , (2) 4 to 6 weeks of inpatient IV antibiotic therapy along with inpatient addiction care services that offered MOUD , (3) 3 weeks of inpatient IV antibiotic therapy along with addiction care services followed by OPAT (OPAT strategy), and 4) 3 weeks of IV antibiotic therapy along with addiction care services followed by partial oral antibiotic therapy .In 3 of the strategies , patients with IDU-IE could receive addiction care services while hospitalized. These strategies were based on the assumption that when addiction care services were implemented, hospitalized individuals would have an increased probability of receiving MOUD in addition to addiction counseling, opioid withdrawal management, long-term medication titration, and referral and linkage to outpatient addiction care at the end of hospitalization.S aureus (non-MRSA) IDU-IE would be eligible to receive oral antibiotic therapy after 3 weeks of hospitalization; however, all patients would be eligible to receive addiction care services. The probability of treatment completion and costs differed for each strategy. Details of these parameters and parameter sources are available in eMethods 1 in the In the OPAT strategy, all hospitalized patients with IDU-IE transitioned to either home-based or outpatient OPAT after 3 weeks of hospitalization and the offer of addiction care services. We assumed that 50% of patients would have home infusion therapy and 50% would receive OPAT at a postacute care facility. This assumption was informed by unpublished data from Boston Medical Center  suggesting that one-half of patients with IDU-IE were homeless and therefore could not be discharged home. For the partial oral antibiotic strategy, we assumed that only patients admitted with non–methicillin-resistant 24 We evaluated LYs rather than quality-adjusted LYs because the interventions focused on mortality-based outcomes, and quality-adjusted LYs are intended to measure life expectancy among patients with diseases in which there is a measurable change in quality of life  and the experience with drug use is heterogeneous. Probabilistic sensitivity, scenario, and threshold analyses were performed to evaluate major findings.The REDUCE model simulated a closed cohort of people who injected short-acting opioid drugs. For this analysis, we simulated a cohort over a lifetime to estimate long-term outcomes, including the mean percentage of patients completing treatment for IDU-IE, deaths associated with IDU-IE, life expectancy (measured in life-years [LYs]), mean cost per person, and incremental cost-effectiveness ratios (ICERs). We compared costs using a payer system perspective and denominated currency in 2020 US dollars. We discounted all costs and benefits by 3% annually and expressed ICERs as cost per LY gained, with a willingness-to-pay threshold of $100 000 per LY.3 The model simulated a closed cohort experiencing the natural history of injection opioid drug use. Individuals moved through time in weekly steps from model initialization until death. Each week, there was a probability of developing sequelae of injection opioid drug use , requiring hospitalization, receiving outpatient addiction care, and changing injection drug use behavior.The REDUCE model has been described in detail elsewhere.The simulated cohort was stratified by sex , age (0-99 years), and injection behavior profile, which included injection frequency , sharing of injection equipment , and sterile injection technique   informed the rates of hospitalization, the probability of initiating MOUD while an inpatient, and the association of addiction care services and MOUD with injection frequency. We assumed that 26% of individuals accepted addiction care services while inpatients based on unpublished data from Boston Medical Center addiction care services .49 The probabilities of completing OPAT and partial oral antibiotic therapies were informed by data from the published literature.8We assumed that individuals receiving inpatient addiction care services and MOUD had a 70% probability of linking to outpatient MOUD compared with individuals receiving inpatient MOUD alone (45% linkage), individuals receiving addiction care services alone (57% linkage), and individuals not receiving either inpatient MOUD or addiction care services (5% linkage). We estimated the conditional probabilities of linking to outpatient MOUD based on data from cohort studies and clinical trials.55 To account for additional opioid drug use–associated harms not captured by fatal overdose or IDU-IE, we multiplied the resulting mortality rates by 1.2.54After accounting for fatal overdose, we derived age- and sex-adjusted mortality rates from the National Vital Statistics System to inform mortality associated with competing risks.64 and the Medical Expenditure Panel Survey25 , and Excel software (Microsoft Corporation). No significance tests were performed for this simulation study.68 At model initialization, the mean age of the cohort was 42 years , 70% were male, 53% had high-frequency injection drug use, 11% had low-frequency injection drug use, and 36% had no current injection drug use.68 We assumed imperfect access to harm reduction services, with 66% of the cohort practicing unsterile injection techniques and 45% sharing injection equipment.69We initialized the model with a cohort of 5 million individuals who reflected the age and sex of the US population who inject opioid drugs, with data informed by the US Census and published literature.Over a lifetime horizon within the usual care strategy, 685 637 individuals developed IDU-IE, 557 386 were hospitalized with IDU-IE, and 250 654 died of IDU-IE. The usual care strategy resulted in 18.63 LYs; 77.6% of hospitalized patients with IDU-IE completed treatment, and 5.01% of deaths in the population attributable to IDU-IE . Life exThe usual care strategy yielded a discounted lifetime mean cost of $416 570 per person  whereas the OPAT strategy was the least expensive at $412 150 per person  compared with the partial oral antibiotic strategy  and the usual care/addiction care strategy . The usual care strategy was dominated by  all other strategies. Compared with the OPAT strategy, the partial oral antibiotic strategy had an ICER of $163 370 per LY. The usual care/addiction care strategy was dominated by the partial oral antibiotic strategy.In the scenario analyses, the partial oral antibiotic strategy was preferred  when patients with MRSA-associated IDU-IE were assumed to be eligible to receive partial oral antibiotic therapy, when treatment uptake of partial oral antibiotic therapy or OPAT was held equal, and when the inpatient stay was decreased and treatment uptake of partial oral antibiotic therapy was increased . IncremeClinicians have expressed concern regarding the possibility of overdose while receiving outpatient antibiotic therapy. In a scenario quadrupling the rate of overdose in the community, our findings regarding improved outcomes with partial oral antibiotic and OPAT regimens did not qualitatively change. The OPAT strategy was the least expensive at $312 670 per person compared with the partial oral antibiotic strategy ($313 930 per person) and the usual care/addiction care strategy ($316 250 per person) and resulted in 0.059 additional LYs. The partial oral antibiotic strategy had an ICER of $167 410.We performed several threshold analyses. First, because uncertainty remained regarding the comparative benefit of IV vs partial oral antibiotic therapies, we performed a threshold analysis of the minimum benefit of both partial oral antibiotic and OPAT strategies, lower than which the usual care strategy provided the best outcomes . We founNext, we explored the rate at which patients accepted a given therapy. When OPAT uptake decreased from 100% to 79%, OPAT was no longer the preferred strategy because the mean discounted cost of OPAT ($413 860) became equivalent in cost to the partial oral antibiotic treatment strategy ($413 920). When partial oral antibiotic therapy uptake increased from 79% to 86%, partial oral antibiotic therapy was the preferred strategy, with an ICER of $72 182 per LY , but administration of OPAT within in a postacute care facility rather than a hospital may be preferable to both approaches. However, the high rate of adverse events associated with OPAT, including peripherally inserted central catheter line infection and thrombosis, will need to be considered when discussing alternative antibiotic therapy strategies.73 examining the efficacy of a partial oral antibiotic regimen for patients with early patient-directed discharge is currently being conducted, and model parameters are within the currently observed range. Second, although important model parameters were informed by studies of the target population, unmeasured confounders may have impacted the results of these studies. Despite these limitations, our findings did not qualitatively change in sensitivity analyses and when varying assumptions were used, which may enable clinicians and hospital staff to consider these findings within their local context.This study has several limitations. First, we relied on a single published study to inform parameters on partial oral antibiotic treatment completion and regimen costs. However, a prospective cohort study26 Those savings could be shifted to programs that specifically address the opioid epidemic, such as initiatives to improve access to MOUD, promote safer injection techniques, and provide multidisciplinary outpatient support systems, including peer navigators and case managers, to decrease the future incidence of IDU-IE and support patient retention in substance use disorder care programs.Results from this decision analytical modeling study suggest that, if implemented, the strategies could save the health care system a substantial amount of money in lifetime hospitalization costs alone for the estimated 750 000 individuals currently injecting drugs in the US.


Effects of different surface textures on the interface shear strength, interface slip, and failure modes of the concrete-to-concrete bond are examined through finite element numerical model and experimental methods in the presence of the horizontal load with ‘push-off’ technique under different normal stresses. Three different surface textures are considered; smooth, indented, and transversely roughened to finish the top surfaces of the concrete bases. In the three-dimensional modeling via the ABAQUS solver, the Cohesive Zone Model (CZM) is used to simulate the interface shear failure. It is observed that the interface shear strength increases with the applied normal stress. The transversely roughened surface achieves the highest interface shear strength compared with those finished with the indented and smooth approaches. The smooth and indented surfaces are controlled by the adhesive failure mode while the transversely roughened surface is dominated by the cohesive failure mode. Also, it is observed that the CZM approach can accurately model the interface shear failure with 3–29% differences between the modeled and the experimental test findings. The composite concrete slab is constructed by integrating a precast concrete slab with the cast-in-place concrete topping, both of which are performing monolithically in unison as a single element as dictated by their shear strength at the interface. The interfacial behavior of composite concrete slab plays an imperative role in maintaining its integrity in service. In essence, the cohesion and frictional characteristics of concrete, as well as its external normal stress all contribute to the capacity of the composite action near the interface region of the slab –3. The set al. [et al. [et al. [et al. [A significant number of experimental studies have revealed that the interface shear strength relies greatly on the roughness and the adhesive type of the composite interface. Loov and Patnaik  pointed et al. , Ceia et [et al. , and He  [et al.  observed [et al.  stated t [et al.  showed ttechniques have been established to model the fracture or debonding of the interface layers through the fracture mechanics and strength of materials methods [et al. [et al. [Over the past decades, various  methods –17. As a methods  and Bare methods  is a fra methods ,21. They methods  presente [et al.  implemen [et al. . Hadjazi [et al.  establis [et al. . The modIt is worth noting that most of the aforementioned experimental studies considered only the horizontal loading case. However, in reality, the vertical load occurs also on the top layer of the composite precast slab during service. For the composite slab to behave monolithically, the bond at the interface between the precast slab and concrete topping must remain intact. The interface shear stress must be sufficiently transferred along the interface of the two concretes. However, when load is applied on the weaker interface bond, it may cause interface failure due to slippage of the concrete topping. If this slip occurred and the composite action is lost, only friction force is acted between the precast slab and concrete topping. Therefore, each concrete layer will deform separately due to the vertical forces which cause tension at the bottom of the two concretes. Therefore, this study was aimed to investigate the effects of the surface texture roughness on the interface shear strength, interface slip, and failure mode of the interface of the concrete-to-concrete composite under both horizontal and vertical loading using the “push-off” test method. To evaluate the quality of the surface which ranges from very smooth to very rough (limited to the roughness height) and is significantly influenced by the method of preparation as per Eurocode 2 , smooth et al. [2 and 40 N/mm2. In preparation, the concrete topping was cast onto the concrete base after confirming that the concrete base had achieved two-third of the design compressive strength at 7 days.The “push-off” test used to study the behavior of the interface bond of the composite concrete-to-concrete slab under different normal stresses. The test was conducted following the approach adopted in Mohamad et al. . A total2, 0.5 N/mm2, 1.0 N/mm2, and 1.5 N/mm2. To avoid any uplift during the test, a uniformly arranged set of rollers was placed on top of the specimen. The horizontal displacement or interface slip was measured during the test using the Linear Variable Displacement Transducer (LVDT) close to the interface as shown in fct is the lower concrete tensile strength among the two layers, σn is the normal stress strength, and μ is the friction coefficient compatible with the interface shear strength given as:Rpm is the mean peak height roughness parameter while the theoretical cohesion coefficient, C, takes the following expression:The interface shear strength was determined based on the shear-friction theory for the surface texture types examined in this study as follows :τ=C.fctIn addition to the physical tests, the “push-off” tests were simulated by the 3D FE models using the commercial software, ABAQUS 6.12/standard . Fig 6 s2, 1.0 N/mm2, and 1.5 N/mm2 for different normal stress loading conditions. For the control specimen where the normal stress was 0 N/mm2, the top surface was restrained in the y- and z-directions. In the third step, the load was applied as a displacement, δ, monotonically in the x-direction until the interface slipped and the loading curve experienced a drop in magnitude. The application of loading on the composite concrete used the kinematic coupling constraint, in which a large number of nodes  were constrained to the rigid body motion of a single reference point located centrally at the side of the concrete topping.The interaction characteristics of the interface element introduced between the concrete base and concrete topping were modeled in accordance with the interface failure modes demonstrated in the experimental tests. Accordingly, the interaction of the interface element was modeled adopting the tie constraint description for the smooth and indented surfaces due to the observed adhesive bond failure. On the other hand, for the transversely roughened surface, the interface failed with the cohesive mode. To model such a condition, the interface element was inserted through the concrete topping. Meanwhile, the rough interface for the concrete-to-concrete bond was modeled as the cohesive interaction instead of an element-based interfacial description see . To perf2 and 31 kN/mm2, respectively, as obtained from the experimental tests. The concrete base and concrete topping models were meshed using the 3-dimensional solid elements. The element type employed for the smooth surface specimen was an 8-node linear bricks  with reduced integration and hourglass control (C3D8R) while those with indented and transversely roughened surfaces were meshed with 6-node linear triangular prism elements (C3D6). The selection of different types of continuum elements was due to differences in the surface textures. The 3-dimensional interface element (COH3D8) with zero-thickness was embedded in the model via shared nodes or tie constraints to connect the concrete topping and concrete base.The concrete base and concrete topping were modeled as elastic materials with Young’s Moduli of 35 kN/mmGIC = GIIC = GIIIC = GTC. The critical fracture energy (GTC) was determined as:S is the peak shear load and δ is the displacement at failure.The CZM parameters were then used to describe the interface shear behavior of the models. The employed CZM included the constitutive relation between the traction acting on the interface and the corresponding interface separation (displacement or slip at the interface). The traction-separation law was applied by assuming the isotropic condition in the fracture energy, in which The elastic modulus of the traction-separation law was obtained as the initial slope that relates the interface shear strength to the displacement given as:tn is the normal traction, ts and tt are the transverse tractions, and The onset interface shear failure takes place when the corresponding interface traction exceeds its maximum interface shear strength. The model interface shear strength was considered as isotropic. The damage was assumed to initiate when the quadratic interaction function containing the interface shear stress  ratios reaches 1.0. The relevant expression is:Gshear = GII+GIII, GT = GI+Gshear, and η is the BK material parameter. For isotropic failure, GIC = GIIC and η was taken as 1.In the analysis, the energy-based Benzeggagh-Kenane (BK) damage evolution criterion given as:The obtained interface properties for the composite concrete are summarized in The refinement meshes for monolithic plain concrete were carried out for all the surface textures with the element size of 5 mm, 15 mm, and 20 mm. From the converged outcome, an average element size of 20 mm was considered in all the models. The employed numbers of nodes and elements for each model are summarized in The horizontal load-interface slip relationship was plotted for each normal stress loading condition. The interface shear strength was determined from the average maximum value of all nodes on the interface layer.2 to 1.5 N/mm2. At the attainment of the failure load, slipping was developed and eventually resulted in the separation from the two concrete layers.The relationships of horizontal load and interface slip in the presence of normal stresses for different surface textures are shown in After the peak shear load was reached, a linear drop trend can be observed in the load magnitude following the increment of the interface slip, indicating the beginning of interface bond failure. The corresponding lowest load magnitudes were close to 0 kN for all the specimens except in some cases depending on the applied normal stress. The state at which the peak load is attained before the concrete layers are separated is referred to as the pre-crack interface shear strength. During the early loading process, both the interface slip and the horizontal load increased gradually under the static friction condition. In this stage, the horizontal load broke the interface bond by exceeding the pre-crack interface shear strength. The transversely roughened surface specimens recorded the greatest peak shear loads ranging from 311.77 kN to 577.30 kN for all normal stress conditions before the interface bond was broken. This was followed by the specimens with the indented surfaces and then those with smooth surfaces with peak shear loads between 136.73 kN and 335 kN as well as between 60.3 kN and 178.3 kN, respectively, as exhibited in In the simulation, the damage initiation was computed at the peak shear load while the propagation was initiated at the softening portion of the curve. It can be seen in σn = 0 N/mm2, 0.5 N/mm2, 1.0 N/mm2, and 1.5 N/mm2, respectively. The specimen under σn = 0 N/mm2 shows that its corresponding horizontal load increases linearly with a clear yield. At this point, the plasticity takes place with little hardening in following the perfectly plastic properties. In the FE model, the elastic behavior of the interface layer was assumed as isotropic for the concrete topping, hence, the slight difference in stiffness between the FE model and the experimental test. However, the linear elastic behavior of the FE model at σn = 0.5 N/mm2 is close to the experimental test.The comparative differences in the peak shear loads between the FE model and experimental test are 3.17%, 9.94%, 10.92%, and 4.69% for The load-deformation curves of transversely roughened specimens show that the peak shear loads of both the experimental test and the FE model are close to each other with the percentages of difference ranging from 1.02% to 3.66%. Meanwhile, the interface slips of the experimental specimens at peak shear load are 29.36% and 33.02% lower than the FE model. This is because the surface of the transversely roughened specimen was modeled as cohesive behavior by assuming that the failure occurred at the concrete topping. However, in the experimental test, the interface between the concrete base and concrete topping can be considered as having a full bonding.It was observed that the composite slab failed under the simultaneous actions of normal stress and “push-off” loadings in two specific modes; adhesive and cohesive failures. The rupture of the interface bond is referred to as the adhesive failure, in which separation occurs at the interface zone while the chipping of concrete base or topping is referred to as the cohesive failure. The smooth and indented specimens failed by the adhesive mode where a thin slice of concrete topping adhesive could be detected on the smooth and indented surfaces as depicted in 2 to 1.5 N/mm2.In The interface of the indented model is found to have high stresses at the edge of the composite concrete, which is also at the onset of the crack propagation, as demonstrated in In general, the maximum stresses in all models occurred at the edge of the vicinity of the crack tip nodes in front of the loading point at 10% of the length along the interface leading to a slippage between the two concrete layers. Then, the crack propagated along the interface once the stress began to decrease gradually due to the restraint provided by the surface texture roughness. Then, a sudden failure occurred in the critical region when the stress went outside the cohesive zone to the fracture zone at around 90% of the length along the interface.The ‘push-off’ integrated with the normal stress testing method was employed to study the interface shear properties of the bonding of concrete base and topping. The composite concrete was designed such that the shear failure was the dominating mode. For a detailed understanding of the shear stress formation, FE simulation was also conducted.Based on the findings obtained from the research work, the following conclusions can be drawn:2 to 1.5 N/mm2.The failure shear load increased corresponding to the rise in the normal stress from 0 N/mmThe roughness of the top surface of the concrete base influenced greatly the interface shear strength of the concrete-to-concrete bond, from which the transversely roughened specimen exhibited the highest strength as compared with those with smooth and indented interface with the ranking: Transversely roughened > indented > smooth.A bi-linear relationship was observed in the horizontal load-interface slip curve for all interface textures.The smooth and indented surface textures failed by the adhesive failure mode where a thin slice of the concrete topping adhesive was observed on the top surface of the concrete base. However, the transversely roughened surface was dominated by the cohesive failure mode, in which the concrete chipping was observed on the top surface of the concrete base at failure.The crack tip edges suffered the highest stress caused by the increase of the interface shear stress during loading, which resulted in the breakage of the interface bond.Differences in the interface shear strengths between the FE models and experimental test specimens were 6% to 29%, 4% to 14%, and 3% to 21% for the smooth, indented, and transversely roughened surfaces, respectively, exhibiting good agreement between the two approaches.


Research on the effects of lying and memory is increasingly attracting empirical attention. In the current manuscript, a scientometric analysis was carried out on the mnemonic consequences of lying. This analysis took into account 70 published articles extracted from Scopus and Web of Science databases from 1998 to 2021. A scientometric analysis was conducted in order to visualize the state of the art on this line of research . Additionally, a keywords’ cluster analysis was executed to investigate the main keywords used in the published papers. Based on the keywords’ cluster analysis, we identified the main aims and critical issues of the reviewed papers. The United States and the Netherlands are the two most productive countries into the effects of lying on memory. The top five authors are mainly from European countries and wrote from 6 to 15 articles. The cluster analysis detected three clusters of keywords. The critical issues of this line of research are mainly related to the generalizability of the achieved findings for real situations, a lack of a direct control of the manipulation adopted, and a need of additional measures. The current analysis provides a comprehensive overview and understanding of existing research on the effects of lying on memory and provides possible future directions of this research domain. It has been widely established that several factors  can affect our memory for an event e.g., . Recentl1 , the act of feigning amnesia leads to omissions, while if the liar uses a more elaborated lie , feigning amnesia has been shown to elevate commission errors.Moreover, scholars have found that feigning amnesia can lead to both omissions and commissions depending on the way in which the liar has simulated amnesia . That isforced confabulation paradigm .The search of relevant publications was performed by using two databases: Scopus and Web of Science (WoS).ications . The litA plethora of software is available to analyze data with a scientometric approach . For the current work, VOSviewer was used ; it is aThe number of publications on the effects of lying on memory by countries is shown in An inspection of the number of publications published by country and by year was also conducted. n = 22), Criminology (n = 2), Criminology and Law (n = 1). In the top 10 most productive journals – of which 7 in the research area of Psychology, 2 in Criminology, and 1 in Criminology and Law – 72% (52/70) of the total publications reaching 68.2% of total citations (690/1012) was published. Specifically, only the leading journal  published more than 10 papers on the effects of lying on memory, while three journals  published from 5 to 8 papers, and the rest  from 2 to 4 papers. Regarding the number of citations of the top 10 most productive journals, it is noteworthy that the higher numbers of publications did not necessarily result in having a high number of citations. Indeed, 2 journals  reached a very good performance , 6 journals obtained a good performance , and 2  a moderately good performance . By contrast, four journals that published only one paper reached a very good or good performance with more than 100 or 50 citations.n = 20). However, the majority of the top 10 most productive institutions are located in Europe (n = 7), with a minority in the United States (n = 3). In particular, the leading institutions – having the highest number of publications and TGCS and one of the highest TCpY  – was Maastricht University (the Netherlands), followed by the Catholic University of Leuven (Belgium) and the University of Bari Aldo Moro  with a high number of publications  and high or good TGCS  and TCpY . The rest of the 10 most productive institutions – from the United Kingdom , United States , France (University of Lille), and Sweden (Stockholm University) – had an average number of publications (from 5 to 3), but high or good TGCS (26–61) and TCpY (15.75–2.73). Interestingly, some institutions that published only one article obtained high TGCS and TCpY, i.e., Gustavus Adolphus College , and Montana State University .An analysis on the number of publications on the effects of lying on memory by institutions of the first author was performed. This analysis was performed by considering the country, the total global citation scores (TGCS), and the total citations per year (TCpY). n = 34) of the total publications on the effects of lying on memory of which only 5 were single-authored. The first two authors – Otgaar, H., and Mangiulli, I. – of the top 10 most productive authors had more than 10 publications , followed by Van Oorsouw, K., Zaragoza, M.S. and Battista, F. with more than 5 publications  and the rest of the list with 4 or 3 publications. Of interest, more than half of the most productive authors’ own publications, except Polage, D. C., were multi-authored publications.The analysis on the performance of authors was performed. The top 10 most productive authors based on the number of publications are listed in To verify the co-occurrence relationships among authors, a co-authorship analysis was run. An analysis on the number of citations by authors was performed. A document co-citation analysis (DCA) gives a network of co-cited publications by providing the knowledge base of these publications . SpecifiAn author co-citation analysis (ACA) counts the frequency with which any publication of an author is co-cited with another author in the references of citing documents and, therefore, provides the relationships among authors whose publications are cited in the articles . Figure With the aim to investigate the semantic data of the published studies, a cluster analysis on the Keywords Co-Occurrence Network (KCN) was carried out. A cluster analysis is a statistical technique that permits to identify the relative degree of correlation of terms and classify a large pool of semantic data pertaining to a specific theme into the same group and data pertaining to a different theme into other groups. In this way, it is possible to identify the themes, trends, and association of a corpus of studies . The KeyBased on the cluster analysis, a selected overview was conducted on the publications using the eight keywords detected in the KCN which amounted to a total of 33 publications. The review was done in order to identify the following studies’ information: (i) Main aim, (ii) kind of deceptive strategy employed, (iii) type of stimulus, (iv) type of memory task, (v) significance of the results, and (vi) limitations. We decided to review this information in order to provide information on the main questions investigated in the considered publications by highlighting the adopted methods and by pointing out their limitations. The information “Main aim,” “Deceptive strategy,” “Type of stimulus,” “Type of memory task,” and “Limitations” was simply extracted from each publication and “nd”  was assigned if no information was detected, while for the information “Significance of the results,” we assigned “Yes” if the authors found a statistically significant effect of deception on memory and “No” if the authors did not find any statistically significant effect.4  the main limitations were: (i) the generalizability of the achieved findings for real situations (12 publications), (ii) lack of a direct control of the manipulation (9 publications), (iii) need of additional measures  (4 publications), (iv) not studied mechanisms underpinning the effects of lying on memory (1 publication), (v) need of investigating different kinds of deception simultaneously (2 publications), (vi) need of considering different perspective taking (1 publication). However, for studies with more artificial stimuli  the main limitations were: (i) the generalizability of the achieved findings for real situations (4 publications), (ii) lack of a direct control of the manipulation (1 publication), and (iii) not studied mechanisms underpinning the effects of lying on memory (2 publications).The aim of the present study was to perform a scientometric analysis and provide a selected overview of literature about the effects of lying on memory. Our principal reason for undertaking such analysis was to provide a comprehensive picture of the state of the art on this topic and identify needs for future research topics. We performed a literature search by using Scopus and Web of Science and we collected 70 publications from 1998 to 2021 (October 21st). Our results showed the following.5, while a peak of publications in recent years, specifically from 2018 to 2021, was registered for the Netherlands, Italy, and Belgium 6. Therefore, this seems to suggest that these last three countries were the ones that recently were mostly involved in the investigation of the effects of lying on memory by strengthening international collaborations. In addition, these results underline that a gap between the United States and European countries  is increasing in the last years resulting in a leading role of the European countries in this line of research.To begin with, a performance analysis was conducted on countries, journals, institutions, and authors’ performance. The United States was the leading country in terms of the amount of publications on the effects of lying on memory followed by the Netherlands. Most publications from the United States were single country publications suggesting that they were not the result of international collaborations. By contrast, publications from the Netherlands – and the other countries  – were mainly multilab publications, thus demonstrating that this line of research encouraged collaborations among scholars of different countries. It is interesting to mention that when we further investigated countries’ performance, we found that this index is strictly related to the year of publications. That is, we found that the United States published a high number of publications from 1998 to 2014 (24/28)In order to understand a possible reason for these results, we checked if this shift in countries’ performance could correspond to a switch of attention in the deceptive strategy investigated and whether authors mentioned in their manuscript a reasoning why they were interested in a specific deceptive strategy. Most studies (70%) conducted in the United States aimed to investigate the effects of fabrication on memory, while European countries also conducted research on the effects of false denials and feigning amnesia . Consequently, the peak of publications from 2018 to 2021 suggests that the shift in countries was also a shift in research into the memory effects of different strategies of deception. Interestingly, the general reasoning reported by the authors to examine the effects of deceptive strategies on memory was similar in the majority of the publications regardless of the country. Indeed, in around 70% of publications, the authors argued to be interested in reproducing the real legal situations in which people deceive in an experimental setting. This argumentation was also provided in publications from American and European countries and both before and during the peak of publications (2018–2021).However, when we looked specifically at the legal cases provided as examples in which different kinds of deception can occur, we found different reasons based on the type of deception investigated. In particular, 24 studies on fabrication referred to legal cases in which interviewers used suggestive tactics forcing the interviewee  to provide information . Specifically, in several of these studies, these cases referred to situations in which children were interviewed and pressured to provide information. In contrast to this, in all publications on feigning amnesia, the authors examined this deceptive strategy because they related it to cases in which offenders use this strategy in order to obstruct investigations and interfere with legal proceedings. Finally, the main reason in publications on false denials (17 publications) was that victims of sexual abuse sometimes falsely deny being abused because they do not want to disclose a traumatic event . Specifically, while presenting examples of real cases, scholars mostly reported situations in which children who are victims of sexual abuse deny such abuse during the very first interviews and come forward with the truth in later interviews. These different reasons provide a plausible explanation for the interests of different types of deception on memory across time.Applied Cognitive Psychology with more than ten publications. This is not surprising considering that this journal has specific attention for studies on autobiographical memory, the detection of deception, eyewitness memory, and statement reliability. The other journals publishing a high number of publications (5–8 publications) were Memory, Memory and Cognition, and Acta Psychologica. Again, this was not surprising based on the aim of the journals, Memory and Memory and Cognition, i.e., publishing experimental work in all the areas of memory and cognition . In addition, based on the scope of Acta Psychologica to publish a broader range of psychological research areas , the high number of publications in this journal leads to the conclusion that scholars published their work on the effects of lying on memory not only in journals with a specific focus on how memory works, but also in journals promoting more general areas. This probably results from a desire of scholars to make this work visible to a higher number of people due to the strong practical implications of this work for practitioners .Regarding the performance of journals, more than 70% of publications was published in 10 journals. The first journal was Applied Cognitive Psychology and Memory and Cognition had a high performance in terms of citations with more than 100 citations. However, we additionally discovered that the number of publications in journals did not necessarily reflect the quantity of citations. Indeed, on the one hand, we found that many of the most productive journals did not have a high or good performance in terms of citations, while on the other hand, some of the journals that published only one paper reported a high performance in terms of citations. A possible explanation for this could be that the citation score strictly depends on specific indexes of the journals  that permit a large spreading of the publications. Therefore, a comparison of the performance among journals based on the number of citations might not provide accurate information on journals’ productivity.Moreover, we took into consideration the journals’ citation scores and we again found that Concerning the institutions’ performance, the analysis showed that – even if more than half of the institutions are based in the United States – the most productive institutions were from Europe, with Maastricht University (the Netherlands) being the most productive together with the Catholic University of Leuven (Belgium) and the University of Bari Aldo Moro . This is in line with our results on countries’ performance by time showing that in the last years the geographic area mainly involved in the investigations of the effects of lying on memory has shifted from the United States to Europe. Once again, the citation scores  did not go at the same pace as the number of publications. Based also on the countries’ performance by time, it could be argued that the citation scores of some of the European most productive institutions were lower than other American less productive institutions because the publications from such American institutions were published many years before the European ones. This could have made such publications more detectable and citable.Finally, regarding the analysis on performance, the one conducted on authors’ performance demonstrated that the most two prolific authors with more than 10 publications were Otgaar, H. and Mangiulli, I., followed by van Oorsouw, K., Zaragoza, M.S. and Battista, F. (8–6 publications).When a co-authorship analysis was executed, the same authors – plus Curci, A. and except Zaragoza, M.S., – were detected to be the scholars that stimulated collaborations among scholars. This was also confirmed with the type of publications, i.e., single-author or multi-author, showing that none of the above-mentioned authors published single-author studies.The further analysis on the frequency with which publications and authors were cited  and co-cited  showed interesting results. Specifically, we first found that the most cited publications were articles published from the 1998 to 2001 e.g., . This seThe cluster analysis conducted on authors’ keywords allowed us to identify the most used keywords gathering in clusters. Because our aim was to summarize the main trends within the literature on the effects of lying on memory, we set a co-occurrences threshold using the default value among those available. Hence, we distinguished three clusters and eight keywords meaning that the most representative and used keywords used in publications on the effects of lying on memory are eight and can be collapsed in three major groups. In particular, examining the detected keywords for each cluster, the first cluster identified keywords more related to the publication on the false denial strategy, the second cluster on feigned amnesia and fabrication, while the third cluster included general keywords not attributable to the investigation of a specific deceptive strategy. Hence, based on the identified clusters, it is reasonable to argue that a high number of publications are only centered on the mnemonic effects of false denials, while publications on the consequences of feigned amnesia and fabrication on memory are more related to each other.The cluster analysis was also used to select the publications on which we conducted a further investigation. The review was done in order to better understand the main issues investigated so far and how they were investigated with the final aim to provide helpful suggestions for future research. Hence, we critically reviewed the aims, methods, and limitations of the selected studies. The combination of this information allows to have a more comprehensive understanding of the studies published so far and can be summarized as follows. Concerning the main goals addressed in the selected studies, the majority of the studies examined the effects of lying on memory by considering the effects of each deceptive strategy  at once, while just a few compared two strategies in only one study. Additionally, a few studies were interested in understanding how lying can change people’s beliefs in the occurrence of false events. Finally, only one study addressed whether and how repeatedly lying affects liars’ memory. In addition, the event information on which participants had to lie upon was mainly presented by using a video of a mock crime video  or by asking them to perform actions . Interestingly, only the minority of studies used pictures or narratives. Moreover, the memory scores used to test a possible impairment in terms of forgetting or memory distortions  due to having lied were free recall scores or source monitoring scores.It is noteworthy to underline that some studies used in their experiment multiple types of memory scores, like for instance both recognition and cued recall scores or cued and free recalls. All the findings observed in these studies were statistically significant and, specifically, demonstrated that overall lying on an event leads to a detrimental effect on memory. Finally, when we looked at the limitations stated by the authors in their papers, almost all the scholars indicated as a principal issue the impossibility to completely generalize the findings in real situations due to several reasons . In partTaken together, our scientometric analysis has several implications. First, the general picture is that lying can adversely affect memory. This conclusion seems to be supported by the different type of stimuli and memory tasks adopted. Indeed, although studies used different materials and measures in accordance with the specific goal of the study, the recurrent finding was that there is a statistically significant difference between liars and truth-tellers in the recall of the original event and that such a recall is worst in liars than in truth-tellers. However, to truly capture this effect, meta-analytic studies should be conducted on the effect of lying on memory. Second, because the main goal of the studies was to test each strategy at once, there is also a large consensus on the idea that each strategy affects memory in its own way. This is in line with the main assumption of the Memory and Deception model MAD; . HoweverWe have presented the first scientometric analysis on the effects of lying on memory combined with a selected review. By adopting this combined review approach, we were able to provide relevant information on research not only in terms of countries, institutions, journals, and authors’ performance but only in terms of detection of the research themes, methodology, and limitations, and challenges for future research. Our findings showed that the  investigation of the effects of lying and memory is increasing in the last years . The number of collaborative actions among scholars seems to be limited to few authors, suggesting that the research on this topic has captured the attention of a small group of researchers belonging to the same community. In addition, the selected review highlighted the need to continue investigating the topic by adopting more ecological paradigms and trying to provide information on un-answered questions.This work provides useful information for researchers interested in investigating how lying affects memory by underlying that this line of research is an emerging field that necessitates further attention.https://osf.io/xe4ty/.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: Open Science Framework: FB conceived the study, conducted data searching, analyzed the data, and wrote the manuscript. HO critically revised the manuscript. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Biliary strictures caused by inflammation or fibrosis lead to jaundice and cholangitis which often make it difficult to distinguish malignant strictures. In cases when malignancy cannot be excluded, surgery is often performed. The concept of immunoglobulin G4 (IgG4)–related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed. The high prevalence of the disease in Asian countries has resulted in multiple diagnostic and treatment guidelines; however, there is need to formulate a standardized diagnostic strategy among various countries considering the utility, invasiveness, and cost-effectiveness. We evaluated accuracies of various diagnostic modalities for biliary strictures comparing pathology in the Delphi meetings which were held in Rochester, MN. The diagnostic utility for each modality was graded according to the experts, including gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan. Diagnostic utility of 10 modalities, including serum IgG4 level, noninvasive imaging, endoscopic ultrasound, endoscopic retrograde cholangiopancreatography–related diagnostic procedures were advocated and the reasons were specified. Serum IgG4 level, noninvasive imaging, diagnostic endoscopic ultrasound and intraductal ultrasonography under endoscopic retrograde cholangiopancreatography were recognized as useful modalities for the diagnosis. The information in this article will aid in the diagnosis of biliary strictures particularly for distinguishing IgG4–SC from cholangiocarcinoma and/or primary SC. Inflammatory or fibrotic strictures of the biliary system typically lead to jaundice and cholangitis, which are associated with high patient morbidity. Appropriate treatment is dependent on an accurate clinical diagnosis, which can often be challenging. Surgery is often performed when malignancy cannot be excluded, but this may be avoidable in some circumstances.,The concept of immunoglobulin G4 (IgG4)–related sclerosing cholangitis (SC) as a benign biliary stricture was recently proposed.The high prevalence of IgG4-RD in Asian countries has resulted in multiple publications and guidelines; however, there is need to formulate a standardized diagnostic strategy considering the differences in the utility, invasiveness, and cost-effectiveness of diagnostic modalities. Therefore, we convened Delphi meetings of expert gastroenterologists, endoscopists, radiologists, and pathologists from the United States and Japan to discuss diagnostic strategies for biliary strictures, and particularly for distinguishing IgG4-SC from cholangiocarcinoma and/or primary sclerosing cholangitis (PSC). Diagnostic utility for each modality was graded as 1 (high), 2 (medium), or 3 (low) . When rehttp://mcpiqojournal.org): type 1 is stenosis only in the lower common bile duct, occasionally misdiagnosed as pancreatic cancer or cholangiocarcinoma; type 2 is stenosis diffusely distributed throughout the intra- and extrahepatic bile ducts, sometimes misdiagnosed as PSC; type 3 is stenosis in both the hilar hepatic region and the lower common bile duct; and type 4 is stricture in only the hilar hepatic region. Types 3 and 4 are occasionally misdiagnosed as cholangiocarcinoma. In a recent Japanese survey, 87% of IgG4-SC cases were associated with AIP.The Japanese clinical practice guidelines for IgG4-SCP<.001).Stricture of the lower common bile duct can be caused by compression due to AIP. Type 1 IgG4-SC is less common in patients with focal-type AIP with only body and tail involvement compared to head involvement  for the evaluation of biliary strictures for possible IgG4-SC relates to the ability to identify the involvement of other organs associated with IgG4-RD, particularly classic abnormalities of the pancreatic parenchyma. Although imaging sequelae of cirrhosis may potentially support a diagnosis of PSC, IgG4-SC can also lead to secondary biliary cirrhosis, so this is not specific. The presence of satellite lesions in the liver would clearly favor a diagnosis of cholangiocarcinoma.Diagnostic utility 1 for contrast-enhanced CT is considered when it is able to detect dilation or wall-thickening biliary abnormalities, metastasis of cholangiocarcinoma, and/or other organ involvement in patients with IgG4-RD.Diagnostic utility 1 for MRI/MRCP is considered when it is able to detect stenosis or dilation of the bile ducts; an image of the entire biliary system is needed. Cholangiography or pancreatography under MRCP is minimally invasive, but does not always yield diagnostic images.Although commonly performed for the evaluation of patients with known or suspected AIP, the sonographic abnormalities of the pancreas on EUS are not well characterized. Rather, the primary role of EUS is to perform fine-needle aspiration (FNA) to rule out pancreatic malignancy. However, the evaluation of wall thickening with or without biliary stenosis can distinguish IgG4-SC from cholangiocarcinoma. In fact, EUS can often show bile duct wall thickening that is more extensive than visualized with noninvasive imaging. Few reports have described EUS findings of IgG4-SC.EUS-FNA of the bile duct is occasionally useful for diagnosing cholangiocarcinoma, but one must take special care due to the risk of tumor seeding and/or bile leakage. A recent meta-analysisDiagnostic utility 1 for diagnostic EUS is considered when it enables with high accuracy the detection of pancreatic swelling in patients with AIP. Furthermore, evaluation of wall thickening with or without stenosis can distinguish IgG4-SC from cholangiocarcinoma.Diagnostic utility 2-3 is considered for EUS-FNA of the bile duct, and it is not recommended due to the risk of seeding and/or bile leakage, but may be useful if the tumor is large enough to puncture.The role of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and management of AIP has evolved over time. In early experience with AIP, most patients underwent ERCP for treatment of jaundice.,,Brush cytology is frequently used to detect bile-duct malignancy, and, in the United States, to rule out malignancy in patients with PSC with a dominant stricture. Although brush cytology enables the detection of malignancy, qualitative diagnosis is difficult, and 3% to 15% of benign cases are reportedly misdiagnosed as cholangiocarcinoma.Diagnostic utility 3-2 is considered for brush cytology from the bile duct) as there is low sensitivity for detecting cholangiocarcinoma, and there is risk for false-positive diagnoses.,To diagnose bile-duct stricture caused by cancer, biopsy at the time of ERC can be useful. Although specificity of biopsy under ERC was 97%, sensitivity was only 56%.Diagnostic utility 2-3 is considered for biopsy under ERC from the bile duct as biopsy under ERC is useful for diagnosing bile-duct stricture caused by cancer. However, it cannot be used to detect pathological indicators of IgG4-SC or PSC.,The IDUS findings of strictures and nonstrictured segments of the bile duct can enable the differentiation of IgG4-SC from cholangiocarcinoma . CirculaDiagnostic utility 1 is considered for IDUS because IDUS findings of strictures and non-strictures of the bile duct enable differentiation of IgG4-SC from cholangiocarcinoma. Symmetrical wall thickening involves both strictured and nonstrictured portions in IgG4-SC.,ERC is useful for diagnosing IgG4-SC, and particularly for its differentiation from PSC.Diagnostic utility 1-2 is considered for cholangiography because ERC is useful for differentiating IgG4-SC from PSC. A cholangiogram is required for biliary drainage, and IDUS and biopsy are needed to rule out cholangiocarcinoma.,Cholangioscopy enables detailed examination of the structure of the bile-duct mucosa . From prRegardless of the difficulty, cholangioscopy is important to improve the targeting of bile duct biopsies. Therefore, cholangioscopy has a potential to distinguish IgG4-SC from cholangiocarcinoma and PSC.Diagnostic utility 2 is considered for cholangioscopy as detailed structures of the bile duct mucosa can be observed. It aids in diagnosis by improving the targeting of bile duct biopsies, but is not diagnostic alone. Further improvement of image quality and establishment of diagnostic criteria based on high-quality images are needed.Diagnosing biliary strictures is complex but can be facilitated by using complementary modalities. The information in this article will aid in the diagnosis of biliary strictures, particularly IgG4-SC.