我国ICD-10疾病分类编码质量的系统评价

目的 基于文献,系统评价我国出院疾病诊断分类的编码质量。方法 计算机检索SINOMED(CBMdisc)、中国知网（CNKI）、维普数据库（VIP）、万方数据库,并辅以文献追溯的方法,收集2000-2014年间在国内公开发表的所有住院病历出院疾病编码错误率的文章。按纳入和排除标准筛选文献并评价其质量,采用描述性分析方法对编码质量进行定性系统评价。结果 纳入30篇文献中,19篇报道了总体编码错误率,研究对象为全部或大部分疾病10篇,仅针对特定种类或某专科疾病的文献9篇,编码错误率中位数分别是12.99%和20.41%,两者间差异无统计学意义,P＝0.121。编码错误率与时间无关但与研究样本量存在负相关关系,r_s＝-0.702,P＝0.001。16篇报道主要诊断编码错误率的文献中,8篇报道了主要诊断总错误率,11篇文献报道了主要诊断选择的错误率,错误率中位数分别为24.77%和5.17%。结论 我国编码质量水平总体上与现有标准仍存较大差距,政策制定者、医院管理者及病案编码人员应采取更有效措施来缩小差距,提高编码质量。

     

Use of CRISPR/Cas9 gene editing to improve chimeric antigen-receptor T cell therapy: A systematic review and meta-analysis of preclinical studies

BackgroundChimeric antigen-receptor T (CAR-T) cells represent great promise in cancer treatment. CRISPR/Cas9 gene editing in preclinical studies has enabled the development of enhanced CAR-T products with improved function and reduced toxicity.MethodsA systematic review of preclinical animal studies was conducted to determine the efficacy and safety of this approach.Results3753 records were identified (to September 9, 2020), with 11 studies using CRISPR/Cas9 gene editing in combination with CAR-T therapy against human cells in animal models of acute leukemia (four studies), glioma (two studies), melanoma (two studies), and other cancers (three studies). Compared with unedited controls, gene-edited CAR-T cells reduced tumor volume in treated animals and improved survival. No adverse side effects were reported. Use of allogeneic “third-party” CAR-T cells appears feasible. Improved efficacy was achieved through both knock-in and knockout gene editing of various targets implicated in immune function. Targeting multiple genes also appears feasible. Significant heterogeneity in study design and outcome reporting was observed, and potential bias was identified in all studies.Conclusion: CRISPR/Cas9 gene editing enables manufacturing of CAR-T cells with improved anti-cancer effects. Future studies should reduce unintentional bias and heterogeneity of study designs and strive to augment long-term persistence of edited cells.Protocol registration: PROSPERO; registration number CRD42020220313 registered November 30, 2020     

Association between comorbidity and participation in breast and cervical cancer screening: A systematic review and meta-analysis

BackgroundComorbidity is associated with poor outcomes for cancer patients but it is less clear how it influences cancer prevention and early detection. This review synthesizes evidence from studies that have quantified the association between comorbidity and participation in breast and cervical screening.MethodsPubMed, CINAHL and EMBASE databases were systematically searched using key terms related to cancer screening and comorbidity for original research articles published between 1 January 1991 and 21 March 2016. Two reviewers independently screened 1283 studies that met eligibility criteria related to Population (adult, non-cancer populations), Exposure (comorbidity), Comparison (a ‘no comorbidity’ group), and Outcome (participation in breast cancer or cervical screening). Data was extracted and risk of bias assessed using a standardised tool from the 22 studies identified for inclusion (17 breast; 13 cervical). Meta-analyses were performed for participation in breast and cervical screening, stratified by important study characteristics.ResultsThe majority of studies were conducted in the United States. Results of individual studies were variable. Most had medium to high risk of bias. Based on the three “low risk of bias” studies, mammography screening was less common among those with comorbidity (pooled Odds Ratio 0.66, 95%CI 0.44–0.88). The one “low risk of bias” study of cervical screening reported a negative association between comorbidity and participation.ConclusionWhile a definitive conclusion could not be drawn, the results from high quality studies suggest that women with comorbidity are less likely to participate in breast, and possibly cervical, cancer screening.     

Congenital Anomalies in Children Exposed to Antithyroid Drugs In-Utero: A Meta-Analysis of Cohort Studies

BackgroundHyperthyroidism affects about 0.2%-2.7% of all pregnancies, and is commonly managed with antithyroid drugs (ATDs). However, previous studies about the effects of ATDs on congenital anomalies are controversial. Therefore, the present meta-analysis was performed to explore the risk of congenital anomalies in children exposed to ATDs in-utero.MethodsEmbase, Pubmed, Web of Knowledge, and BIOSIS Citation Index were searched to find out studies about congenital anomalies in children exposed to ATDs in-utero reported up to May 2014. The references cited by the retrieved articles were also searched. The relative risks (RRs) and confidence intervals (CIs) for the individual studies were pooled by fixed effects models, and heterogeneity was analyzed by chi-square and I² tests.ResultsEight studies met the inclusion criteria. Exposure to propylthiouracil (PTU), methimazole/carbimazole (MMI/CMZ), and PTU & MMI/CMZ was investigated in 7, 7 and 2 studies, respectively. The pooled RR was 1.20 (95%CI: 1.02-1.42), 1.64 (95%CI: 1.39-1.92), and 1.83 (95%CI: 1.30-2.56) for congenital anomalies after exposure to PTU, MMI/CMZ, and PTU & MMI/CMZ, respectively.ConclusionsThe meta-analysis suggests that exposure to ATDs in-utero increases the risk of congenital anomalies. The use of ATDs in pregnancy should be limited when possible. Further research is needed to delineate the exact teratogenic risk for particular congenital anomaly.     

Systematic review of studies of patient satisfaction with telemedicine

ObjectiveTo review research into patient satisfaction with teleconsultation, specifically clinical consultations between healthcare providers and patients involving real time interactive video.DesignSystematic review of telemedicine satisfaction studies. Electronic databases searched include Medline, Embase, Science Citation Index, Social Sciences Citation Index, Arts and Humanities Citation Index, and the TIE (Telemedicine Information Exchange) database.SubjectsStudies conducted worldwide and published between 1966 and 1998.Results32 studies were identified. Study methods used were simple survey instruments (26 studies), exact methods not specified (5), and qualitative methods (1). Study designs were randomised controlled trial (1 trial); random patient selection (2); case-control (1); and selection criteria not specified or participants represented consecutive referrals, convenience samples, or volunteers (28). Sample sizes were ≤20 (10 trials), ≤100 (14), >100 (7), and not specified (1). All studies reported good levels of patient satisfaction. Qualitative analysis revealed methodological problems with all the published work. Even so, important issues were highlighted that merit further investigation. There is a paucity of data examining patients'' perceptions or the effects of this mode of healthcare delivery on the interaction between providers and clients.ConclusionsMethodological deficiencies (low sample sizes, context, and study designs) of the published research limit the generalisability of the findings. The studies suggest that teleconsultation is acceptable to patients in a variety of circumstances, but issues relating to patient satisfaction require further exploration from the perspective of both clients and providers.     

Discovery of a series of small molecules as potent histone deacetylase inhibitors

Abstract

A series of small molecules were designed and synthesized based on our previous virtual screening approach, which was performed to discover potent histone deacetylase inhibitors (HDACIs) with novel structures. The derived compounds were tested by Hela cell nucleus extract for enzyme inhibition assay. Tumor cell growth inhibition assays were performed using a series of tumor cell lines. Molecule 4h has the best performance among these compounds with enzyme inhibition IC₅₀ of 0.14?μM and tumor cell growth inhibition IC₅₀ of 1.85 (U937), 2.02 (HL60), 2.67 (K562). Docking studies showed that multiple H-bonds and hydrophobic interactions make 4h binding to the active site of HDAC. 4h has the advantage of low molecular weight, so a variety of structural modifications can be performed in our further studies.     

Epidemiology of leptospirosis in Tanzania: A review of the current status,serogroup diversity and reservoirs

BackgroundTanzania is among the tropical countries of Sub-Saharan Africa with the environmental conditions favorable for transmission of Leptospira. Leptospirosis is a neglected zoonotic disease, and although there are several published reports from Tanzania, the epidemiology, genetic diversity of Leptospira and its host range are poorly understood.MethodsWe conducted a comprehensive review of human and animal leptospirosis within the 26 regions of the Tanzanian mainland. Literature searches for the review were conducted in PubMed and Google Scholar. We further manually identified studies from reference lists among retrieved studies from the preliminary search.ResultsWe identified thirty-four studies describing leptospirosis in humans (n = 16), animals (n = 14) and in both (n = 4). The number of studies varied significantly across regions. Most of the studies were conducted in Morogoro (n = 16) followed by Kilimanjaro (n = 9) and Tanga (n = 5). There were a range of study designs with cross-sectional prevalence studies (n = 18), studies on leptospirosis in febrile patients (n = 13), a case control study in cattle (n = 1) and studies identifying novel serovars (n = 2). The most utilized diagnostic tool was the microscopic agglutination test (MAT) which detected antibodies to 17 Leptospira serogroups in humans and animals. The Leptospira serogroups with the most diverse hosts were Icterohaemorrhagiae (n = 11), Grippotyphosa (n = 10), Sejroe (n = 10), Pomona (n = 9) and Ballum (n = 8). The reported prevalence of Leptospira antibodies in humans ranged from 0.3–29.9% and risk factors were associated with occupational animal contact. Many potential reservoir hosts were identified with the most common being rodents and cattle.ConclusionLeptospirosis is prevalent in humans and animals in Tanzania, although there is regional and host variation in the reports. Many regions do not have information about the disease in either humans or their animal reservoirs. More studies are required to understand human leptospirosis determinants and the role of livestock in leptospirosis transmission to humans for the development of appropriate control strategies.     

Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis

Background aimsSeveral studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI.MethodsSystematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled.ResultsA total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were –2.78 (95% confidence interval [CI] –5.12 to –0.43, P = 0.02), –18.26 (95% CI –26.09 to –10.43, P < 0.01), –17.08 (95% CI –24.10 to –10.07, P < 0.01) and –4.37 (95% CI –10.96 to 2.22, P = 0.19), respectively.ConclusionsMSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy.     

Copper(II), cobalt(II) and nickel(II) complexes of lapachol: synthesis,DNA interaction,and cytotoxicity

Three novel copper(II), cobalt(II), and nickel(II) complexes of lapachol (Lap) containing 110-phenanthroline (phen) ligand, [M(Lap)₂(phen)] (M=Cu(II), 1, Co(II), 2, and Ni(II), 3), have been synthesized and characterized using, elemental analysis and spectroscopic studies. Their interactions with calf thymus DNA (CT DNA) were investigated using viscosity, thermal denaturation, circular dichorism, fluorescence quenching, and electronic absorption spectroscopy. The DNA cleavage abilities of 1–3 have been studied, where cleavage activity of copper complex 1 is more than the complexes 2 and 3. The in vitro cytotoxic potential of the complexes 1–3 against human cervical carcinoma (HeLa), human liver hepatocellular carcinoma (HepG-2), and human colorectal adenocarcinoma (HT-29) cells indicated their promising antitumor activity with quite low IC₅₀ values in the range of .15–2.41 μM, which are lower than those of cisplatin.     

Diagnostic value of GLUT-1 in distinguishing malignant mesothelioma from reactive mesothelial cells: a meta-analysis

Abstract

Background: Previous studies have demonstrated the diagnostic value of glucose transporter 1 (GLUT-1) to distinguish malignant mesothelioma (MM) from reactive mesothelial cells (RMC), but the results are inconsistent. The purpose of this meta-analysis is to investigate the diagnostic accuracy of GLUT-1 in distinguishing MM from RMC.

Methods: A systematical search was conducted until May 2019 in PubMed, Medline, Embase and the Cochrane Library. The revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2) was used to assess the quality of the eligible studies. The Stata15 and Review Manager5.3 software programmes were used to perform the meta-analysis.

Results: A total of 24 studies, including 969?MM patients and 1080 RMC individuals were explored in the meta-analysis. The summary assessments revealed that the pooled sensitivity was 0.73 (95% CI, 0.62–0.81) and the pooled specificity was 0.95 (95% CI, 0.91–0.98). The area under the summary ROC curve (AUC) was 0.93 (95% CI: 0.91–0.95).

Conclusions: GLUT-1 is highly accurate to distinguish MM from RMC.     

Pyrazole Related Nucleosides 5.1 Synthesis and Biological Activity of 2′-Deoxy- 2′, 3′-dideoxy- and Acyclo-analogues of 4-Iodo-1-β-D-ribofuranosyl-3-carboxymethyl Pyrazole (IPCAR)

Abstract

Continuing our studies on the structure-activity relationships (SAR) of 4-iodo-1-β-D-ribofuranosyl-3-carboxymethyl pyrazole (IPCAR), the ribofuranosyl moiety has been substituted with acyclic chains, namely 1-[(2-hydroxyethoxy)methyl]- and 1-[(1,3-dihydroxy-2-propoxy)methyl]-pyrazole derivatives (4, 5 and 8, 9 respectively), with the 2′-deoxy-β-D-ribofuranosyl group (12 and 13) and finally with the 2′,3′-dideoxy-D-glycero-pentofuranosyl-moiety (16 and 17). None of the new compounds display any interesting biological activity.     

Cognition of and Demand for Education and Teaching in Medical Statistics in China: A Systematic Review and Meta-Analysis

BackgroundAlthough a substantial number of studies focus on the teaching and application of medical statistics in China, few studies comprehensively evaluate the recognition of and demand for medical statistics. In addition, the results of these various studies differ and are insufficiently comprehensive and systematic.ObjectivesThis investigation aimed to evaluate the general cognition of and demand for medical statistics by undergraduates, graduates, and medical staff in China.MethodsWe performed a comprehensive database search related to the cognition of and demand for medical statistics from January 2007 to July 2014 and conducted a meta-analysis of non-controlled studies with sub-group analysis for undergraduates, graduates, and medical staff.ResultsThere are substantial differences with respect to the cognition of theory in medical statistics among undergraduates (73.5%), graduates (60.7%), and medical staff (39.6%). The demand for theory in medical statistics is high among graduates (94.6%), undergraduates (86.1%), and medical staff (88.3%). Regarding specific statistical methods, the cognition of basic statistical methods is higher than of advanced statistical methods. The demand for certain advanced statistical methods, including (but not limited to) multiple analysis of variance (ANOVA), multiple linear regression, and logistic regression, is higher than that for basic statistical methods. The use rates of the Statistical Package for the Social Sciences (SPSS) software and statistical analysis software (SAS) are only 55% and 15%, respectively.ConclusionThe overall statistical competence of undergraduates, graduates, and medical staff is insufficient, and their ability to practically apply their statistical knowledge is limited, which constitutes an unsatisfactory state of affairs for medical statistics education. Because the demand for skills in this area is increasing, the need to reform medical statistics education in China has become urgent.     

Is Helicobacter pylori associated with non-ulcer dyspepsia and will eradication improve symptoms? A meta-analysis

ObjectivesTo examine the association between Helicobacter pylori infection and non-ulcer dyspepsia, and to assess the effect of eradicating H pylori on dyspeptic symptoms in patients with non-ulcer dyspepsia.DesignSystematic review and meta-analysis of (a) observational studies examining the association between Helicobacter pylori infection and non-ulcer dyspepsia (association studies), and (b) therapeutic trials examining the association between eradication of H pylori and dyspeptic symptoms in patients with non-ulcer dyspepsia (eradication trials).Results23 association studies and 5 eradication trials met the inclusion criteria. In the association studies the summary odds ratio for H pylori infection in patients with non-ulcer dyspepsia was 1.6 (95% confidence interval 1.4 to 1.8). In the eradication trials the summary odds ratio for improvement in dyspeptic symptoms in patients with non-ulcer dyspepsia in whom H pylori was eradicated was 1.9 (1.3 to 2.6).ConclusionsSome evidence shows an association between H pylori infection and dyspeptic symptoms in patients referred to gastroenterologists. An improvement in dyspeptic symptoms occurred among patients with non-ulcer dyspepsia in whom H pylori was eradicated.     

Associations of genetic polymorphisms in CTLA-4 and IL-18 with chronic liver diseases: Evidence from a meta-analysis

BackgroundThe aim of this meta-analysis was to explore associations between polymorphisms in CTLA-4/IL-18 and chronic liver diseases by combing the results of all relevant studies.MethodsEligible studies were searched from Pubmed, Embase, Web of Science and Cochrane library. We used Review Manager to combine the results of eligible studies.ResultsSixty-seven studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs231775 (dominant, recessive and allele comparisons), IL-18 rs1946518 (dominant, recessive and allele comparisons) and IL-18 rs187238 (dominant, over-dominant and allele comparisons) polymorphisms were all significantly associated with chronic liver diseases in the overall population. We also obtained similar positive results for rs231775, rs5742909, rs3087243, rs1946518 and rs187238 polymorphisms in subgroup analyses by ethnicity and type of disease.ConclusionsThis meta-analysis demonstrated that CTLA-4 rs231775, CTLA-4 rs5742909, CTLA-4 rs3087243, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to certain types of chronic liver diseases.     

Bisphosphonate Use and Risk of Implant Revision after Total Hip/Knee Arthroplasty: A Meta-Analysis of Observational Studies

ObjectiveSeveral studies investigated the association between bisphosphonate use and the risk of implant revision after total hip or knee arthroplasty (THA or TKA); However, the findings were inconsistent. We performed this meta-analysis to evaluate the overall relative risk of such an event.MethodsWe searched the PubMed, EMBASE and Cochrane library databases to identify relevant publications on April 22, 2015. To calculate the pooled risk ratios (RRs) with 95% confidential intervals (CIs), a fixed- or random-effects model was applied based on the heterogeneity across studies.ResultsThree cohort studies and one case-control study were included in this meta-analysis. Compared with the bisphosphonate nonusers, the patients who used bisphosphonates for a long period of time had a significantly decreased risk of implant revision after THA/TKA (summary adjusted RR = 0.48, 95% CI: 0.38–0.61), and the summary adjusted RRs for the users who underwent THA and those who underwent TKA were 0.47 (95% CI: 0.36–0.61) and 0.45 (95% CI: 0.21–0.95), respectively.ConclusionsLong-term use of bisphosphonates is correlated with a significantly decreased risk of implant revision after THA/TKA. However, due to limited number of the included studies, the findings of the present study should be treated with caution. More well-designed studies are required to further confirm our findings.     

Systematic review on medicinal plants used for the treatment of Giardia infection

BackgroundHowever, broad adoption of herbal remedies for giardiasis is at present hampered by uncertain findings of investigation not always sufficiently powered. This study was aimed at systematically reviewing the existing literature in herbal medicines to treat giardiasis.MethodsThis review was carried out 06- PRISMA guideline and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. The search was performed in five databases which are Scopus, PubMed, Web of Science, EMBASE, and Google Scholar without time limitation for all published articles (in vitro, in vivo, and clinical studies). The searched words and terms were: “Giardia”, “giardiasis”, “extract”, “essential oil”, “herbal medicines”, “anti-Giardia”, “In vitro”, “In vivo”, “clinical trial” etc.ResultsOut of 1585 papers, 40 papers including 28 in vitro (70.0%), 7 in vivo (17.5%), 2 in vitro/ in vivo (5.0%), and 3 clinical trials (7.5%) up to 2020, met the inclusion criteria for discussion in this systematic review. The most widely used medicinal plants against Giardia infection belong to the family Lamiaceae (30.0%) followed by Asteraceae (13.5%), Apiaceae (10.5%). The most common parts used in the studies were aerial parts (45.0%) followed by leaves (27.4%) and seeds (7.5%). The aqueous extract (30.0%), essential oil (25.4%) and hydroalcholic and methanolic (10.5%) were considered as the desired approaches of herbal extraction, respectively.ConclusionThe current review showed that the plant-based anti-Giardia agents are very promising as an alternative and complementary resource for treating giardiasis since had low significant toxicity. However, more studies are required to elucidate this conclusion, especially in clinical systems.     

Efficacy and safety of leadless pacemaker: A systematic review,pooled analysis and meta-analysis

BackgroundLeadless pacemakers have been designed as an alternative to transvenous systems which avoid some of the complications associated with transvenous devices. We aim to perform a systematic review of the literature to report the safety and efficacy findings of leadless pacemakers.MethodsWe searched MEDLINE and EMBASE to identify studies reporting the safety, efficacy and outcomes of patients implanted with a leadless pacemaker. The pooled rate of adverse events was determined and random-effects meta-analysis was performed to compare rates of adverse outcomes for leadless compared to transvenous pacemakers.ResultsA total of 18 studies were included with 2496 patients implanted with a leadless pacemaker and success rates range between 95.5 and 100%. The device or procedure related death rate was 0.3% while any complication and pericardial tamponade occurred in 3.1% and 1.4% of patients, respectively. Other complications such as pericardial effusion, device dislodgement, device revision, device malfunction, access site complications and infection occurred in less than 1% of patients. Meta-analysis of four studies suggests that there was no difference in hematoma (RR 0.67 95%CI 0.21–2.18, 3 studies), pericardial effusion (RR 0.59 95%CI 0.15–2.25, 3 studies), device dislocation (RR 0.33 95%CI 0.06–1.74, 3 studies), any complication (RR 0.44 95%CI 0.17–1.09, 4 studies) and death (RR 0.45 95%CI 0.15–1.35, 2 studies) comparing patients who received leadless and transvenous pacemakers.ConclusionLeadless pacemakers are safe and effective for patients who have an indication for single chamber ventricular pacing and the findings appear to be comparable to transvenous pacemakers.     

Synthesis and biological evaluation of biguanide and dihydrotriazine derivatives as potential inhibitors of dihydrofolate reductase of opportunistic microorganisms

Twenty-one biguanide and dihydrotriazine derivatives were synthesized and evaluated as inhibitors of dihydrofolate reductase (DHFR) from opportunistic microorganisms: Pneumocystis carinii (pc), Toxoplasma gondii (tg), Mycobacterium avium (ma), and rat liver (rl). The most potent compound in the series was B2-07 with 12?nM activity against tgDHFR. The most striking observation was that B2-07 showed similar potency to trimetrexate, ～233-fold improved potency over trimethoprim and ～7-fold increased selectivity as compared to trimetrexate against tgDHFR. Molecular docking studies in the developed homology model of tgDHFR rationalized the observed potency of B2-07. This molecule can act as a good lead for further design of molecules with better selectivity and improved potency.     

Variability of salivary markers of oxidative stress and antioxidant status in young healthy individuals

Objectives: Salivary advanced glycation end-products (AGEs), advanced oxidation protein products (AOPP), total antioxidant capacity (TAC), and ferric reducing ability of saliva (FRAS) are increased in various diseases. Little data exist for these markers in the healthy population. The aim of this study was to assess the inter-individual and intra-individual variability of AGEs, AOPP, TAC, and FRAS in the saliva of young healthy individuals.

Methods: Unstimulated saliva samples were collected from 16 females and 18 males daily over a period of 30 days. Markers were measured using spectrophotometric and spectrofluorometric microplate-based methods.

Results: All salivary markers measured were significantly higher in men than in women (P?<?0.05 for AGEs; P?<?0.001 for AOPP, TAC, and FRAS). The inter-individual variability was approximately 60% for AGEs and AOPP and 30–40% for TAC and FRAS in both genders. The inter-individual variability of FRAS was higher in men vs. women (P?<?0.01). Intra-individual variability ranged from 20% for TAC, to 30% for AGES and FRAS and 45% for AOPP.

Discussion: Intra-individual variability of salivary AGEs, AOPP, TAC, and FRAS indicates that their use is currently limited to large cohort studies. Identifying the underlying factors related to the high inter-individual and intra-individual variability is needed. Sex differences should be considered in future studies.