The prediction of the risk of falling remains a challenge in geriatric medicine and the identification of new potential reversible risk factors is a public health priority. In this study, we aim to investigate the association between DAO  and incident falls in a large sample of people with knee OA (osteoarthritis) or at high risk for this condition, over 8 years of follow-up.DAO was defined using a waist circumference more than 102 cm in men and 88 cm in women and a concomitant presence of dynapenia, defined as a time over 15 s in the five times chair stands time. Falls, during follow-up, were recorded using self-reported information in the previous year. A logistic binary regression analysis was run, adjusted for potential confounders at the baseline, reporting the data as odds ratios (ORs) with their 95% confidence intervals (CIs).p = 0.50), whilst the presence of abdominal obesity  and DAO  were significantly associated with a higher risk of incident falls.Overall, 3,844 subjects were included, majority of whom had abdominal obesity. Across the 8 years of follow-up, 2,695 participants fell vs. 1,149 not reporting any fall. Taking those without DAO as reference, the presence of only dynapenia was not associated with risk of falls (OR = 1.18;95%CI: 0.73–1.91; DAO significantly increased risk of falls as well as the presence of abdominal obesity. It has n = 201 females) with 18-months of follow-up also found that DAO was significantly associated with risk of falls (3.6 times) than those without DAO  or at high risk of this condition may be at a greater risk of DAO, independent from already known morbid outcomes such as falls and cardiovascular disease . For exaGiven this background, the aim of the present study was to investigate the association between DAO and incident falls in a large sample of people with knee OA or at high risk for this condition, over 8 years of follow-up.2.2.1.The OAI cohort study is a multi-center, longitudinal, observational study focusing primarily on knee OA . Partici2), family history of knee OA). The baseline assessments consist of an initial eligibility assessment by telephone, a screening clinic visit and an enrollment clinic visit. Several follow-up visits were repeated.The OAI created a public archive of data, biological samples, and joint images collected over time from a very well clinically characterized population of individuals comprised of two subgroups,: (1) had knee osteoarthritis (OA) with knee pain for a 30-day period in the past 12 months or (2) were at high risk of developing knee OA ; education level (categorized as college vs. lower grades); smoking status ; yearly income ; number of alcoholic drinks consumed during a typical week in the last month; physical activity was measured through the Physical Activity Scale for the Elderly scale (PASE) ; the pre2.5.p-values were calculated with the Fisher’s Exact test for frequencies, Mann–Whitney test for medians and independent t-Test for means.Data on continuous variables were normally distributed according to the Kolmogorov–Smirnov test. Data were presented as means and standard deviation values (SD) for quantitative measures  or as medians and interquartile ranges , and percentages for all categorical variables by incidence of falls during follow-up period (yes vs. no). p-value >0.05.Logistic binary regression analysis was run, considering as outcome the incidence of falls during follow-up and as main exposures the presence, at the baseline, of dynapenia and/or abdominal obesity status. Similarly, we reported the associations found for the other control variables. The strength of the association between factors at the baseline and the outcomes of interest were reported as odds ratios (ORs) with their 95% confidence intervals (CIs). To the test the robustness of our results, we did run several sensitivity analyses , but all these interaction reported a p < 0.05 was deemed statistically significant. Analyses were performed using SPSS 26.0.A 3.p < 0.0001 for the comparison).Among the 4,796 participants initially included, 943 did not have sufficient information regarding chair stands time or waist circumference, making it not possible to allocated them to any of the four categories of DAO and nine did not report any information regarding incident falls. Therefore, 3,844 subjects were included. Overall, at the baseline, participants without abdominal obesity and dynapenia included 27.5% of the population, whilst abdominal obesity affected 58.8% of the participants and dynapenia 2.5%. Finally, the co-presence of DAO affected 11.2% of the population examined at the baseline. As expected, the prevalence of radiological knee OA was significantly higher in DAO (79.1%) compared to only obesity (64.6%) and only dynapenia (62.1%) than in people without these two conditions  incident fallers  were more likely to be female (p < 0.0001), but no differences in terms of age was observed (p = 0.21). Incident fallers reported a significantly higher number of medications (p < 0.0001), but a similar rate of comorbidities (p = 0.16). Moreover, they were more depressed and reported a higher presence of previous falls at the baseline (p < 0.0001 for both comparisons).p < 0.0001), but not of dynapenia , whilst the presence of abdominal obesity  and dynapenia and abdominal obesity  were associated with a higher risk of incident falls. Among the other factors considered, being females, white, and highly educated were associated with a higher risk of falling during the follow-up. Moreover, higher values of alcohol drinking in a typical week, CES-D, PASE, number of medications as well as falls reported before the baseline had a significant higher risk of falling during the 8 years follow-up.4.In this large study of North American people affected by knee OA or at high risk for this condition with over 8 years of follow-up, we found that abdominal obesity and DAO, in particular, were associated with a higher incidence of falls, even after controlling for multiple confounders. On the contrary, dynapenia alone was not associated with incident falls.Our analyses showed that being female, white, highly educated, drinking high levels of alcohol, depressed, and using an elevated number of medications were significant factors for falls, overall confirming previous research . The finFindings from the present study and that of previous research  suggest The findings of our work must be interpreted within its limitations. First, several variables used in the analysis including falls were self-reported, potentially introducing a recall bias. Second, the OAI includes only people with knee OA or at high risk for this condition: therefore, this population is not representative of the general population. Third, handgrip strength was not available in the OAI dataset and, therefore, it is possible that people with knee OA may do badly on chair stands time due to pain. Fourth, the changes of anthropometric parameters and knee OA status were not included in the analyses, but they may affect our results. Finally, it is possible for DAO status or other control variables to have changed during the follow-up, but we did not assess these changes that could modify our results.In conclusion, in the present study including a large representative sample of adults participating in the Osteoarthritis Initiative, over 8 years of follow-up, it was observed that DAO significantly increased risk of falls as well as the presence of abdominal obesity. Therefore, interventions to prevent or reverse dynapenic abdominal obesity may be beneficial for fall reduction, a phenomenon that afflict several people with important consequences.The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author.The OAI study was given full ethics approval by the institutional review board of the OAI Coordinating Center, at the University of California in San Francisco, CA, USA. The patients/participants provided their written informed consent to participate in this study.NV drafted the first version of the manuscript and made the statistical analysis. AK supervised the statistical analysis and critically revised the manuscript. PS drafted the first version of the manuscript. FB contributed to the data collection and drafted the first version of the manuscript. LD, MB, SS, NA-D, and LS critically revised the manuscript. All authors contributed to the article and approved the submitted version.The OAI is a public-private partnership comprised of five contracts  funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the OAI Study Investigators. Private funding partners include Merck Research Laboratories; Novartis Pharmaceuticals Corporation, GlaxoSmithKline; and Pfizer, Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Private sector funding for the OAI is managed by the Foundation for the National Institutes of Health. This manuscript was prepared using an OAI public use data set and does not necessarily reflect the opinions or views of the OAI investigators, the NIH, or the private funding partners. The authors extend their appreciation to the Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia for funding this research (IFKSURC-1-1602).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.


The main objective of this systematic review was to synthesize the evidence on the occurrence and characteristics of stuttering in individuals with Down syndrome and thus contribute knowledge about stuttering in this population. Group studies reporting outcome measures of stuttering were included. Studies with participants who were preselected based on their fluency status were excluded. We searched the Eric, PsychInfo, Medline, Scopus, and Web of Science Core Collection databases on 3rd January 2022 and conducted supplementary searches of the reference lists of previous reviews and the studies included in the current review, as well as relevant speech and language journals. The included studies were coded in terms of information concerning sample characteristics, measurement approaches, and stuttering-related outcomes. The appraisal tool for cross-sectional studies (AXIS) was used to evaluate study quality. We identified 14 eligible studies, with a total of 1,833 participants  between 3 and 58 years of age. The estimated occurrence of stuttering ranged from 2.38 to 56%, which is substantially higher than the estimated prevalence (1%) of stuttering in the general population. The results also showed that stuttering severity most often was judged to be mild-to-moderate and that individuals with Down syndrome displayed secondary behaviors when these were measured. However, little attention has been paid to investigating the potential adverse effects of stuttering for individuals with Down syndrome. We judged the quality of the evidence to be moderate-to-low. The negative evaluation was mostly due to sampling limitations that decreased the representability and generalizability of the results. Based on the high occurrence of stuttering and the potential negative effects of this condition, individuals with Down syndrome who show signs of stuttering should be referred to a speech and language pathologist for an evaluation of their need for stuttering treatment. Studies in which the author(s) stated that they investigated stuttering were included. To answer the research questions, only studies that included occurrence estimates of stuttering (% and/or number) were eligible for inclusion. Thus, studies with samples that were preselected based on fluency status were excluded. Studies that investigated the co-existence of stuttering and other developmental speech disorders were included if the stuttering data were separated from other types of data. Mixed-etiology studies were considered for inclusion if they reported separate results for the participants with Down syndrome.2.2We developed the search strategy using words related to Down syndrome and stuttering. The search was conducted on 3rd January 2022 in the following databases: PsycINFO , MEDLINE , Eric , Scopus (from 1960 onward), and Web of Science Core Collection (from 1945 onward). See 2.3The study-selection process had two phases. First, we screened the headings and abstracts and retrieved full-text sources that seemed to meet our inclusion criteria, as well as full-text sources that required further inspection. Second, we assessed the eligibility of these full-text sources. If a source appearing in our search was a chapter in an anthology, we read that specific chapter. When the source appearing in our search was a complete book, we first screened the index and then read the chapter(s) that were relevant to the topic of stuttering and/or disorders of intellectual development. See 2.3.1p < 0.001. Disagreements (n = 18 of 137 sources) were resolved through discussions between the review authors, including a reexamination of the headings and abstracts. In these discussions, the review authors were equal in status. Most disagreements concerned the reason for exclusion . See The authors individually screened all titles and abstracts yielded by the systematic search against the eligibility criteria. Inter-rater reliability was calculated based on the agreement between the review authors regarding whether to include or exclude a study, as well as the reason for exclusion. There was good agreement between the review authors, κ = 0.715 , 2.3.2A total of 33 sources were sought for retrieval based on the systematic search. Of these 33 sources, we were able to retrieve full-text manuscripts from 32. Additionally, we sought full-text manuscripts of potentially relevant sources located through supplementary searches . The supplementary searches revealed 25 sources, Of these 25 sources we were able to retrieve full-text manuscripts from 21. This included our own study , which wA total of 52 sources were assessed against the eligibility criteria in the full-text assessment phase. Three sources were assessed in collaboration between the review authors for training purposes . During κ = 0.749 , p < 0.001. Disagreements (n = 7 of 45 sources) were discussed and resolved between the two review authors, who were equal in status. Four of the disagreements concerned whether a source met the inclusion criteria. The remaining three disagreements concerned the reason for exclusion. The disagreements were resolved through a reexamination of the text and, on one occasion, making contact with the main author of one study for clarification , p < 0.001, to very good, κ = 1.000 , p < 0.001. See A total of 14 studies were eligible for inclusion. We extracted information related to sample characteristics, measurement approaches, and outcomes. We developed the coding scheme for the data extraction and discussed the content of each category. Then, we selected four sources  that we 2.5The appraisal tool for cross-sectional studies (AXIS) was used to assess the quality of the included studies. The tool includes items assessing sampling, justifications, clarity, and precision in descriptions of aims/objectives, methods, and results, as well as the reliability and validity of the measurement instruments see . For stuκ = 0.630 , p < 0.001, to very good, κ = 1.000 , p < 0.001. See Again, one source  publishe2.6We estimated the occurrence of stuttering in the total sample, per gender and per age group, by combining all samples included in the current review.Occurrence = /total N.In the data synthesis, we used the occurrence estimates reported in each individual study, independent of how stuttering was operationalized, thus combining different operationalizations of stuttering. Furthermore, we evaluated sample characteristics, measurement approaches, and stuttering outcomes by conducting a narrative synthesis of the findings consisting of statistical  and narrative (content comparisons and grouping in overarching categories) analyzes. The results are presented in text and table format.33.1n = 6), (2) a search of the reference lists of previous reviews (n = 6), and (3) the reference lists of included studies (n = 1). See A total of 14 studies met the eligibility criteria for inclusion in the current review. One study was the authors’ own study , which w3.2n = 10) having been published before 2000.The included studies were published between 1955 and 2022 and, as such, represent seven decades of research on stuttering in individuals with Down syndrome. However, most of the studies are older, with a majority  stuttering behaviors were considered clinically significant . See Tab3.4In two studies, stuttering was assessed indirectly through parental reports . As the In 12 studies, stuttering was identified through clinical judgment by either SLPs/SLP students and/or the researcher(s) themselves . In eigh3.5M = 131.29, SD = 227.85, median = 45.5) individuals with Down syndrome participated in the included studies, with sample sizes ranging from 26 to 897 participants. A total of 1,833  resulted in an occurrence estimate of 19.80%. Occurrence by gender or the information necessary to calculate occurrence by gender was reported in five studies . The res3.7n = 20) were prolongations, which occurred in 19 of 20 participants, and 22% were part-word repetitions, which occurred in 17 of 20 participants.Stuttering frequency in individuals who stuttered was reported in four studies . The appStuttering severity was reported in six studies. In half of these studies , judgmenSecondary behaviors were reported in six studies . Four ofOutcomes related to the potential adverse effects of stuttering were reported in three studies , all of 3.83.8.1Inter-rater reliability was given for some or all stuttering measures reported in three of the included studies . See Tab3.8.2M = 11.07, SD = 3.99). Thus, the results of the quality appraisal indicate that the quality of the included studies ranges from low to high, with most studies being of moderate-to-low quality. Many studies were found to be lacking in areas related to sampling procedures. First, most studies had small sample sizes, and all studies lacked sample size justifications (AXIS item 3). To provide an example regarding the number of participants necessary for an accurate estimation of stuttering frequency in a population, given an estimated population of 3,725 individuals with Down syndrome in Norway  there was no common approach to identifying stuttering in individuals with Down syndrome, but there was a one-sided focus on observational aspects; (2) the occurrence estimates were generally high but varied across studies; (3) the occurrence estimates were higher in school-aged and adult groups than in the preschool-aged group; (4) the occurrence estimates were higher in male than in female participants; and (5) stuttering was mild-to-moderate, and secondary behaviors were found when measured.To identify stuttering, the included studies used various assessment approaches, which were initially developed for the typically developing population, mainly focusing on the identification of speech disfluencies, both with and without frequency cutoff scores. However, no studies included self-reports of experiences related to stuttering. One reason for the heavy focus on stuttering behavior may be the high frequency of older studies included in this review. The multidimensional view of stuttering may represent a more recent understanding of the disorder, one in line with the changes in the diagnostic criteria for stuttering in the latest revision of the International Classification of Diseases ICD-11, , to inclAlthough the results of this review showed that listener evaluation in the form of clinical judgment was a common approach, the factors considered to be indicative of stuttering varied across studies, especially those related to types of repetition, as did what threshold disfluencies were considered clinically significant. However, research on typically developing individuals faces the same challenges, which means that comparisons are restricted between both the studies in this review and research projects on stuttering in general . The lacIn addition to these general challenges within the field of stuttering related to assessment, there are some specific challenges related to the identification of stuttering behaviors in individuals with Down syndrome. As language development is significantly delayed in this population, there are likely differences in the amount of speech material available for listener evaluation across age groups; preschool-aged children with Down syndrome who have begun to speak will, for example, often produce short utterances . This meThe abovementioned concerns and limitations related to stuttering assessment, in addition to the quality of the included studies, constitute the frame within which we can interpret and understand the findings of the current review. Nevertheless, studies consistently report high occurrences of stuttering in individuals with Down syndrome when interpreted against the estimated 1% prevalence for the typical adult population  across school-aged and adult participants, while in preschool-aged participants, the occurrence estimate was low relative to the cumulative incidence in typically developing children. These results indicate an opposite pattern to that commonly observed in typically developing individuals, in which the occurrence usually is higher in the preschool years and decreases with age . Even thn). This result is in line with findings from studies of the typical adult population, in which more male participants are found to stutter than female participants  sample size, (2) how stuttering is operationalized and assessed, (3) the language proficiency of the participants, and (4) at what age stuttering is measured.Furthermore, because this review is based on only concurrent data regarding stuttering, we do not know how the occurrence rate by age relates to the tractability of stuttering in this population. For example, it is unknown whether those who stutter at young ages continue to stutter later in life. To answer this question, longitudinal studies are needed. Also, as this review only included studies that investigated the occurrence of stuttering, studies with samples preselected based on fluency status have not been included. This implies that there may be more available research investigating the characteristics of stuttering in individuals with Down syndrome that has not been included in this study. Finally, it should be mentioned that some of the confidence intervals in our inter-rater reliability analysis are wide, indicating a limitation in the precision of these estimates. This uncertainty in some of the estimated effect sizes may reflect the low number of studies in this review , as each5The results of this systematic review show a high rate of stuttering occurrence in individuals with Down syndrome, independent of assessors, when interpreted against results derived from studies on occurrence estimates in typically developing individuals. This applies to both male and female participants, but the relative proportion of male participants among stutterers is higher. Furthermore, the occurrence in the school-aged and adult participant groups is especially high. While the operationalization of stuttering varied across the studies, the identification of repetitions, prolongations, and blocks was typically included. Stuttering was commonly judged to be mild-to-moderate, and secondary behavior was found when measured.SH and K-AN: conceptualization, methodology, formal analysis, resources, investigation, data curation, writing–original draft preparation, and writing–review and editing. SH: visualization and project administration: K-AN and SH: funding acquisition. All authors have read and agreed to the published version of the manuscript.


The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED.The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software.Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups.These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED.https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781. Erectile dysfunction (ED) refers to the persistent or recurring phallic erection that is difficult to obtain or maintain enough to meet sexual needs , 2. ED iPriapism is a normal physiological response . When thL-arginine is an amino acid compound obtained by the human body from diet and endogenous metabolism. L-arginine is the substrate of many enzyme pathways involved in the regulation of vascular tone, immune activation, and cell growth . As a suBecause of the limited number of studies available on the combination of PAL in patients with ED, there is a lack of uniform evaluation criteria for efficacy and safety of combination therapy. Therefore, it is necessary to study the efficacy and safety of the combination of PAL in the treatment of patients with ED. To our knowledge, this study is the first meta-analysis to compare their therapeutic effects. It is expected to provide more reliable evidence for the efficacy and safety of the combination of PAL in patients with ED.This study was registered with Prospero (CRD42023411781) and was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis  guidelines .A total of seven commonly used databases were retrieved from the time the database was established until 15 February 2023, specifically PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang database. In addition, unpublished gray literature and references cited in eligible studies were retrieved. We use a search strategy that combines Medical Subject Headings (MeSH) terms with free-text words. For example, when conducting a search in PubMed, the following terms are used: (((“Arginine”[Mesh]) OR (Arginine[Title/Abstract])) AND ((“Pycnogenols” [Supplementary Concept]) OR (((((Pycnogenols[Title/Abstract]) OR (Pinus pinaster bark extract[Title/Abstract])) OR (French maritime pine bark extract[Title/Abstract])) OR (maritime pine bark extract[Title/Abstract])) OR (Pycnogenol[Title/Abstract])))) AND .Articles that fulfilled the following criteria were selected for this study: RCTs in humans with the parallel group or crossover design; the experimental group received a combination of PAL, whereas the control group received placebo at similar intervals; measuring mean changes of outcome indicators, such as international index of erectile function (IIEF) scores (erectile domain), orgasmic function scores, sexual desire scores, intercourse satisfaction scores, overall satisfaction scores, and testosterone (T); data were presented as mean [± standard deviation (SD)] or with 95% confidence intervals (CIs) for the placebo and intervention groups; involving human RCTs published in the English language; reviews, conference abstracts, and studies with unavailable full text were excluded.Two researchers (YT and QZ) extracted articles on the basis of inclusion and exclusion criteria, respectively. Disagreements between the two researchers were resolved by a third reviewer (QC). Excel tables are used to extract and save data. We will extract the following data from the included meta-analyses: first author, time of publication, treatment, country, the total number of cases, number of cases in the experimental group, number of cases in the control group, method of specific treatment for each group, time of therapy, adverse reaction, age, and Body Mass Index (BMI). For articles that lacked sufficient data or where data were not available, we contacted the corresponding author by e-mail for more details. If not, we analyze only the available data.The risk of bias for the included studies was independently assessed by two authors (YT and QZ), and disagreements were resolved by a third reviewer (QC). The methodological quality and bias of all eligible studies were assessed by two independent evaluators using the Cochrane Collaboration’s bias risk tool and standard Excel sheets. Any ambiguity or discrepancy in this course was resolved through discussion and participation of a third person. Using the following seven criteria, we assessed the quality of studies: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessment, (5) incomplete outcome data, (6) selective reporting, and (7) other probable sources of risk biases.2 statistics  and 95% CI. The standard MD is used for the same measure with different measurement methods. We assessed statistical heterogeneity between studies using Cochran Q and Iatistics . This inA total of 25 articles were initially identified through an electronic database search. We import our search results into EndNote V.X9 software. After removing duplicates, reviewing titles and abstracts, and reading through the full text, finally, three articles –26 were The methodological quality and bias of all the eligible studies were assessed using the Cochrane Collaboration’s bias risk tool and standard Excel forms. The risk of bias in the authors’ judgments for each of the included studies is summarized in Effect of combined treatment with PAL on outcome indexes are presented in he= 0.65, I2 = 0%), and a random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed that the combined treatment group was superior to the placebo group in improving IIEF scores (erectile domain) .Among all the included clinical trials, a total of two studies , 26 repohe= 0.76, I2 = 0%), and a random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed that, compared with the placebo group, the combination group is superior in improving the intercourse satisfaction scores .Two studies , 26 repohe= 0.55, I2 = 0%), and a random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed that the combined treatment group improved the orgasmic function scores more than the placebo group .Of all the included clinical trials, a total of two studies , 26 repohe= 0.53, I2 = 0%). Random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed a significant increase in overall satisfaction scores in the combined treatment group compared with that in the placebo group .Overall satisfaction was reported in two studies , 26. Thehe= 0.72, I2 = 0%). Random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed that sexual desire scores in the combined treatment group increased significantly compared with that in the placebo group .Among all the included clinical trials, sexual desire was reported in two studies , 26. Thehe= 0.94, I2 = 0%). Random-effects model was used to combine the effect sizes of clinical studies. Meta-analysis showed that there was no statistical significance in the change of T between the two treatment groups .Two studies , 26 desche= 0.75, I2 = 0%; MD, 13.14; 95% CI, 4.67 to 21.67; P = 0.002). When the intervention duration was 1–3 months, there was a significant difference between the two groups . When the duration of intervention was 3–6 months, the efficacy of the combination treatment group was superior to that of the placebo group . In conclusion, there was no significant difference in the influence of intervention duration on IIEF scores (erectile domain).We performed a subgroup analysis of IIEF scores (erectile domain) on the basis of intervention duration Figure 5The funnel diagram and Egger’s test results produced by Stata 12 software are shown in The results of the funnel plot, the Egger’s test (P = 0.033), and Begger’s test (P = 0.089) show that the analysis for Erectile domain has no publication bias. The results of the funnel plot, the Egger’s test (P = 0.351), and Begger’s test (P = 0.296) show that the analysis for intercourse satisfaction has no publication bias. The results of the funnel plot, the Egger’s test (P = 0.211), and Begger’s test (P = 0.296) show that the analysis for orgasmic function has no publication bias. The results of the funnel plot, the Egger’s test (P = 0.187), and Begger’s test (P = 1.000) show that the analysis for overall satisfaction has no publication bias. The results of the funnel plot, the Egger’s test (P = 0.202), and Begger’s test (P = 0.296) show that the analysis for sexual desire has no publication bias. The results of the funnel plot and Begger’s test (P = 1.000) show that the analysis for T has no publication bias. Perhaps because only two studies were included in the T outcome index, the P-value of Egger’s test was not displayed in the software.ED is a disorder common in men and has extremely serious negative effects on the quality of life of men worldwide . VasculaOne study , which cSeveral limitations should be considered in this systematic review and meta-analysis. Among the three studies included in this meta-analysis, the intervention time of each study was different and varied greatly, which may affect the statistical power. The limitations of this meta-analysis include that similar questionnaires, such as the IIEF scores and IIEF-5 scores used in the included studies, tend to be subjectively evaluated by patients, so proper objectivity of the data cannot be fully obtained. Because of searching Chinese database and screening out zero articles, it is proved that this kind of research is lacking in China, so it is very important to carry out domestic research. The biggest limitation of this paper is that there are few articles included and limited data available for analysis. Therefore, in the future, it will be necessary to conduct more large-scale and well-designed trials to confirm the observations on the efficacy and safety of the combination of PAL for ED.Together, the above findings indicated that the combined treatment of PAL had a significant effect on improving sexual function in aged patients with mild to moderate ED. We hope that this study will provide clinicians with more options for treating patients with ED.The original contributions presented in the study are included in the article/YT and QC contributed to the conception and design of the study. Data collection and extraction were carried out by YT and QZ. WL, ML, and QL planned the data evaluation and statistical analysis. The first draft of the manuscript was written by YT. QC provided guidance and resolved disagreements during this process. All authors contributed to the article and approved the submitted version.


Patellofemoral arthroplasty (PFA) was shown to be a potentially effective surgical technique for isolated patellofemoral osteoarthritis but varying reports on PFA-related implant failure and complications have rendered the procedure controversial. This study aimed to identify impactful publications, research interests/efforts, and collaborative networks in the field of PFA research.The study used the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed to retrieve relevant publications on PFA research published between 1950–2022. Statistical tests in R software were used for analysis while VOSviewer, Bibliometrix, and CiteSpace were employed for data visualization.Knee was the most frequent journal and Clinical Orthopaedics and Related Research was the most cited journal. Clinical outcomes, such as prosthesis survival, revision, and complications, were researched most frequently as demonstrated by keyword analysis. The United States was the top contributor to cooperative networks, followed by the United Kingdom while Technical University Munich formed close ties among authors.Two hundred forty-one articles were analyzed with the number of published papers increasing over time. Publications on PFA research have witnessed a notable surge. They primarily came from a limited number of centers and were characterized by low-level evidence. The majority of studies primarily focused on the clinical outcomes of PFA, while revision of PFA and patient satisfaction have emerged as new research areas.The online version contains supplementary material available at 10.1186/s42836-023-00215-1. Patellofemoral osteoarthritis is a highly prevalent form of osteoarthritis, affecting approximately 25% of those aged 50 and over , 2. Due For all that mounting interest in PFA, a comprehensive analysis of current research in the field, particularly from a bibliometric perspective, is lacking. Bibliometric analysis is a quantitative method that utilizes statistical and mathematical techniques to study citation and publication patterns in a specific field . BibliomIn this study, we aimed to identify the most impactful publications in PFA research and conduct an analysis of their characteristics. Our goal was to provide insights into the current state of the field, identify research gaps, and guide future research directions. We hope that this study will facilitate the development of evidence-based guidelines for the application of PFA in the management of patellofemoral osteoarthritis, thereby improving the quality of care for patients with these conditions.The data were obtained from the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed. Our search strategy consists of “Patellofemoral arthroplasty” OR “Patellofemoral replacement” OR “Patellofemoral joint arthroplasty” OR “Patellofemoral joint replacement”. The publication time of the articles was limited to the period from 1950 to 2022. To avoid bias due to frequent database updates, all our searches and export data were completed on September 19, 2023. The searched and included bibliographies are recorded in Supporting Information, as Tables SBibliographical references from various databases were consolidated to remove duplication. Non-English papers were excluded from the analysis. Papers with unsuitable article types were further excluded by manual persusing the abstracts , remaining publications were further screened by full-text reading. Articles were screened independently by two reviewers. When there was disagreement, a third person performed the consistency assessment. Included item entries for further data collection and extraction.Journal of Bone and Joint Surgery [The articles selected for this study were imported into a reference management software package for further analysis. From these articles, the following data were extracted: author information, including author names, institutions, countries, and corresponding or reprint authors; publication information, such as journal titles, publication year and impact factors; article information, including keywords, major topics, language and level of evidence and citation information, including total number of citations and cited references. The level of evidence was evaluated in accordance with the guidelines set forth by the  Surgery .P < 0.05 (two-sided). R software version 4.2.2 (https://www.r-project.org/about.html) was used for all statistical analyses. To analyze trend changes in the time series data, the Mann-Kendall test was conducted using MATLAB software , with the trend change rate quantified by the uncertainty factor (UF). A positive UF value indicates an increasing trend, while a negative value denotes a decreasing trend.The Kolmogorov-Smirnov test was used to assess the normality of the distribution for individual variables. Normally distributed data were presented as mean ± standard deviation, whereas non-normally distributed data were expressed as medians . Correlation analysis was performed using Spearman’s test and statistical significance was determined at http://www.bibliometrix.org), CiteSpace [https://citespace.podia.com/), MapChart (https://www.mapchart.net), Charticulator (https://charticulator.com), and Microsoft Excel .Histograms and line graphs are used to present overall publication and citation trends, with subsequent trends predicted based on these findings. The relationship between the level of evidence and citations was explored using a box plot, while clustered linkage network plots were utilized to demonstrate relationships between keywords. Line graphs were employed to display the time of occurrence and outbreak of different keywords. A world map marked with shades of color represents the volume of articles published by different countries. Furthermore, to investigate collaboration among different entities, a collaborative network coupled with full-count bibliographic analysis was performed. The data visualization was achieved by using several tools, including VOSviewer  version iteSpace  version After removal of duplicates, a total of 503 bibliographical references were left. Twenty-nine non-English entries were excluded. Manual screening led to the exclusion of 223 entries, 241 articles related to patellofemoral arthroplasty from the year 1979 until 2022 remained. The process for the selection and inclusion of the title catalog is illustrated in Fig. α = 0.01)  . The correlation coefficient (P = 0.285) indicated that there was a positive and moderate association between the level of evidence and the number of citations, suggesting that higher levels of evidence are associated with a greater number of citations.In this study, the median citation counts of articles with level I and level II evidence were 23 0, 46) and 80.5 , respectively. For articles with level III, IV, and V evidence, the median citation counts were 15 , 10 , and 0 , respectively , which was closely followed by Knee Surgery Sports Traumatology Arthroscopy with 25 articles. In terms of citations, Clinical Orthopaedics and Related Research stood out with 951 citations, while Knee secured the second spot with 727 citations. Collectively, these 12 journals contributed to 67.6% of the analyzed articles, underscoring their significance in driving future research. The ten most cited articles from three journals: Knee, Journal of Bone and Joint Surgery-British Volume, and Clinical Orthopaedics and Related Research (Table Clinical Orthopaedics and Related Research. All these articles were published between 2001 and 2007, indicating their lasting relevance.Twelve journals were rated top 10 journals, in terms of number of articles and cumulative citations, Tables . Of notele count 4, which By analyzing the frequency of occurrence, the study employed keyword analysis to reveal research interests and emerging trends in literature. The primary goal was to identify prevailing areas of scholarly concentration/interest in this field. Cluster analysis was utilized to group keywords that appeared five times or more Fig. A. Node sThe present study analyzed articles published by 27 countries or regions, as depicted in a global map (Fig. The analysis of the inter-institutional collaboration network revealed 24 institutions from 8 different countries: the United States, the United Kingdom, France, the Netherlands, Germany, Switzerland, Portugal, and Denmark Fig. C. NotablPFA has emerged as a promising treatment option for patients with isolated patellofemoral osteoarthritis , 27, 28.This study revealed that there was a noticeable increase in article citations and postings around 2006. It was just about ten years after the development of the second-generation prosthesis. And good short- to middle-term follow-up results were reported. Two highly-cited articles , 31 abouThe highly-cited articles mainly originated from the United States and the United Kingdom, with seven of the top ten articles also from these two countries. Our analysis with regard to countries and institutions indicated that the United States and the United Kingdom contributed to over 55% of the articles and about 58.3% of their institutions published more than three articles. This suggests that their researchers or institutions were more active in the field and are more likely to produce new results, which could impact the analysis of highly-cited papers. For instance, the first and second most highly-cited articles were authored by Utting, et al.  and AckrKnee, Knee Surgery Sports Traumatology Arthroscopy, Clinical Orthopaedics and Related Research, and Journal of Bone and Joint Surgery-British Volume. These journals are highly popular with global researchers and have significant impact in the orthopedic community. Interestingly, we observed discrepancies between the top ten journals in the number of articles and citations. These differences may be attributed to variances in the quality of articles appearing in these journals, which may have different publication standards. For instance, some journals may use more rigorous review processes or have stricter criteria for article selection, leading to fewer but high-quality publications. Further research is warranted to identify the factors that may potentially dictate journal rankings and citation outcomes, such as editorial policies, submission trends, and emerging areas of interest in the field of orthopedics.Our investigation into the distribution of journal articles and the journals containing highly-cited articles revealed that these papers were typically found in well-regarded orthopedic journals such as The visual analysis of keywords identified “follow-up”, “outcome”, and “revision” as the focal points of PFA research. Our study found that researchers often reported short- and mid-term outcomes for PFA, which were generally positive –40. UponOur research indicated that the second-generation patellofemoral joint arthroplasties may well be more popular with surgeons and scholars, thanks to their reported superior efficacy and durability when compared to first-generation PFA devices , 43, 44.For the assessment of PFA outcomes, early investigators tended to employ the Hungerford and Kenna knee scoring systems, prosthesis survival rate, as well as radiographs , 45–47. We acknowledge the limitations of our study. Although we searched multiple databases, some were excluded, which may have affected the inclusion of articles. Different databases utilize varying methods for calculating citations, which could have impacted the results. Additionally, recent high-impact articles may have been overlooked due to low citation rates. To address this issue, we recommend selecting comprehensive databases that encompass a wide range of articles. This will mitigate the problem. Furthermore, staying up-to-date with the latest research is essential to our investigation.In the field of PFA research, there has been an increasing trend in publications, with a majority coming from a limited number of centers and a lack of high-level evidence. Most studies have focused on clinical outcomes of PFA, while in recent years, the trend has been shifted towards refurbishment of PFA and patient satisfaction.Additional file 1: Table S1. Detailed bibliographies searched from WOS Core Collection in the field of patellofemoral arthroplasty.  Table S2. Detailed bibliographies searched from Pubmed in the field of patellofemoral arthroplasty.  Table S3. Detailed bibliographies searched from BIOSIS Citation Index in the field of patellofemoral arthroplasty.  Table S4. Detailed bibliographies searched from Springer in the field of patellofemoral arthroplasty. Table S5. Detailed bibliographies searched from Medline in the field of patellofemoral arthroplasty. Table S6. List of bibliographies that meet the criteria and are included in bibliometric analysis.


End-stage renal disease (ESRD) treatment includes dialysis and kidney transplantation. Transplant rejection is a major barrier to transplant success. One of the markers mentioned in previous studies on renal function in patients with renal failure for various reasons is periostin (POSTN). The expression of POSTN correlates with interstitial fibrosis and reduced renal function. One of the limitations in this regard is the effect of oral lesions on the POSTN level. This study was conducted aimed to measure the relationship between salivary and serum POSTN and renal function in patients with a history of a kidney transplant, taking into account all the conditions affecting POSTN.In this study, serum and saliva samples were taken from 23 transplant patients with normal function (NF) and 29 transplant patients with graft failure (GF). At least one year had passed since the transplant. Before sampling, a complete oral examination was performed. Salivary and serum POSTN was examined by ELISA. The results were analyzed by SPSS software.The POSTN level in the serum of the NF group (191.00 ± 33.42) was higher than GF patients (178.71 ± 25.68), but the difference was not significant (P = 0.30). Salivary POSTN in NF patients (2.76 ± 0.35) was significantly higher than GF patients (2.44 ± 0.60) (P = 0.01).The superiority of saliva as a diagnostic fluid includes ease of collection and storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum. Chronic Kidney Rejection (CKR) is a graft failure after one year of transplant in the absence of acute rejection, drug poisoning, and other causes of nephropathy and the main cause is renal allograft failure after transplant . Early dA biomarker is defined as "an index that objectively measures and assesses natural biological processes, and pathogenic or drug responses to a therapeutic intervention" . Also, iPeriostin (POSTN) is a protein in the cell-matrix with a molecular weight of 90 kDa that is expressed by various tissues during embryonic development, but in adults, it is often expressed in collagen-rich connective tissue that is subject to mechanical stress . Cellular matrix proteins are a family including thrombospondins, osteopontin, SPARC, tenascin-C, connective tissue growth factors, and transforming growth factor-β (TGFβ) -inducible factor (βig-H3), of which POSTN is the newest member. POSTN expression is greatly increased following tissue damage. POSTN is directly related to the components of the extracellular matrix and it is assumed that POSTN leads to matrix integrity and affects the biomechanical properties of connective tissue , 5.Over the past few years, POSTN has been recognized as a key factor in the progression of kidney diseases. This protein is secreted very briefly only during kidney development (overnight kidney) and is not normally identified in the adult kidney, but is expressed de novo in the damaged kidney (various forms of CKD). Its expression is correlated with interstitial fibrosis and reduced renal function , 5.In previous studies, tissue and urine POSTN had been suggested as a predictor of graft status , 6. HoweAs serum can indicate systemic disorders, saliva has this ability , 8. SincSince the effects of some oral diseases such as gingivitis and periodontitis, vesicular autoimmune diseases such as pemphigus Vulgaris or bullous pemphigoid , oral liIn this cross-sectional study, we assessed salivary and serum POSTN of KT patients in two subgroups of NF ; transplant patients with normal renal function and GF (graft failure); transplant patients with renal dysfunction, taking into account all known factors affecting POSTN, including oral and maxillofacial lesions and diseases.This cross-sectional study conducted at Urology Research Center, Sina Hospital, Tehran University of Medical Sciences. All experimental protocols were approved by a Tehran University of Medical Sciences Ethics Committee . Written informed consent was also obtained from the patients before entering the study. The study population was selected from renal transplant patients with normal function (NF) (control group), and kidney transplant patients with graft failure (GF) (case group).Inclusion criteria: History of kidney transplantation in more than one year.Exclusion criteria: History of any tumor or neoplasm, congenital cardiovascular disorders, pulmonary fibrosis disorders, scleroderma, allergic disorder, asthma, polycystic kidney disease, type 1 diabetes, pregnancy, autoimmune diseases, active urinary tract infection, liver diseases, other acute or chronic infections and any recent surgery.The mouth of all patients was examined for the presence of various diseases such as gingivitis, periodontitis, and any oral lesions including oral and neck cancer, leukoplakia, lichen planus, and drug-induced gingival enlargement, and for any of these cases, the patient was excluded from this study.To rule out gingivitis, the patient should have gingival index = 0, probing pocket depth and clinical attachment level ≤ 3 mm, no sign of bone loss, and gums have a non-inflammatory texture and natural color. 6 points around each tooth were examined  , 14.The examination was performed by a single examiner with a dental mirror and a Williams sterile probe, gas, and tongue blade. If a more accurate diagnosis is needed, the patient was referred for biopsy, radiographic examinations, and/or other necessary measures for the next stages of diagnosis and treatment of oral lesions (these patients were not entered our study). For this group of patients, a referral and introduction letter were written by the resident for the specialized department of the faculty. After obtaining informed consent, unstimulated saliva and blood samples were taken from all subjects as follows.In this study, 83 kidney transplant patients were examined on an outpatient or inpatient basis. 76 patients had the inclusion criteria included in the questionnaire. Finally, 52 patients after oral examination have entered the study and analysis: 23 kidney transplant patients (44.2%) with normal function (NF) and 29 kidney transplant patients (55%) with graft failure (GF). Based on the renal function (serum creatinine measurement and GFR determination) recorded in the patient’s file at the last visit and in case of dialysis creatinine level before dialysis, the patients were divided into two groups NF (GFR above 60 and creatinine below 120 μmol) (23 patients) and GF (GFR below 30 and creatinine above 150 μmol per liter) (29 patients) [To calculate the sample size regarding EL-Dawla NMQ article  and consDue to the lack of effect of dialysis on POSTN, those with renal dysfunction may be on dialysis treatment. On the one hand, the serum Cr was used to divide patients into NF and GF groups . For the preparation of saliva and blood samples, to prevent changes in circadian rhythm on saliva, all saliva samples were taken in a quiet place at the same time. The unstimulated saliva sample was taken in plastic vials by spitting method after the patient avoided eating, drinking, brushing, taking medication for 90 minutes, and resting for 5 minutes. First, the patient swallowed the saliva in the mouth, and by bending the head forward and eyes open, the slightest movement of the body and head poured the saliva collected in the mouth into a calibrated vial. Saliva volume and time spent salivation were recorded to determine saliva flow and POSTN file in saliva. 5 ml of blood was taken from all patients by the clinic nurse. The samples were centrifuged at 2000 rpm for 10 min. The surface liquid of the samples was immediately frozen and stored at -70° C.POSTN concentration of the samples was examined by ELISA ZellBio GmBH kit (Germany)  and all stages were performed according to the manufacturer’s instructions. This kit is based on Biotin double antibody sandwich technology.The statistical method of POSTN, which is a quantitative variable, was reported as mean and standard deviation. If the data distribution was not normal, the median and IQR were used, and for qualitative (classified) variables, frequency and percentage were used. For the mean comparison of this protein in the two groups, provided that the data are normal, the Kolmogorov-Smirnov test was used. All analyzes with 5% error were performed by SPSS Inc. software. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc.In this study, 83 kidney transplant patients were examined. 76 patients met the inclusion criteria, which included the cases mentioned in the questionnaire. Finally, 52 patients were included in the study and analyzed after the oral examination. The general information of patients is given in The patients underwent a complete oral examination and their saliva and serum samples were prepared, but one of the GF and NF patients refused to give a blood sample and one of the GF and NF patients refused to give a saliva sample.The mean serum POSTN in NF patients was 191.00 ± 33.42 and 178.71 ± 25.68 for GF patients. The distribution of these data based on Kolmogorov-Smirnov was normal. The data were compared by t-test. In NF patients, POSTN was higher than serum POSTN in GF patients, but no significant difference was found (P = 0.30). Based on the ROC test, serum POSTN diagnostic value was measured in these patients, which was not high. Based on the ROC diagram, it can be interpreted that lower serum POSTN can be a diagnostic index of graft failure. Also, the serum cut-off point of 224.75 showed that the specificity of serum POSTN in NF patients was very low (20%) but its sensitivity in GF patients was 96.6%  .Salivary POSTN in NF patients was 2.76 ± 0.35 and 2.44 ± 0.60 in GF patients. After the logarithm test by Kolmogorov-Smirnov, the normal distribution of the results was measured. Therefore, a t-test was selected with a significant difference (P = 0.01). Based on the ROC test, the diagnostic value of salivary POSTN was measured in these patients, and the area under the curve was about 70% and significant (P = 0.01), indicating the high diagnostic value of salivary POSTN. According to the cut-off point of 2.34, in NF patients, salivary POSTN was 95.7% specific , which can be a good test to confirm the diagnosis of transplant patients with normal function. Salivary POSTN also correctly diagnosed 53.6% of GF patients (low sensitivity) with a false negative in 46.4% of GF patients. It was good for confirming the diagnosis of graft failure .No linear relationship was found between salivary and serum POSTN. A 0.30-correlation was found between grafts and salivary POSTN in NF patients, but it was not significant (P = 0.89).A 0.37-correlation was found between the years after transplantation and serum POSTN in NF patients, but it was not significant (P = 0.09). A 0.10-correlation was found between the years after transplantation and salivary POSTN in GF patients, but it was not significant (P = 0.62). A 0.26 correlation was found between the years of transplantation and serum POSTN in GF patients, but it was not significant (P = 0.25).The findings of excluded patients’ oral examinations are shown in In this study, it was shown that salivary POSTN in patients with a history of KT could be a marker for the prognosis of renal function. According to the World Health Organization, a biomarker is "any substance, structure, or process that can be measured in the body or its products and affects or predicts the outcome or disease" . The bioSince KT increases the duration and quality of life of patients, it is the best treatment option for ESRD patients. Despite the advance of KT and immunosuppressive strategies in recent decades, chronic allograft dysfunction remains the biggest concern of these patients, their families, and physicians . Early dThe idea of using saliva biomarkers in KT patients has been mentioned in previous studies. For example, Indoxy Sulphate (IS) (a type of uremic toxin) in saliva was used to predict rejection in KT patients. In this study, as in our results, biomarkers were significant in saliva and insignificant in serum . Also, aCompared to the previous study, in the current study, the oral examination by an oral medicine specialist was done before entering patients to the study for excluding confounder factors related to the salivary POSTN.An increase in POSTN expression in the glomerulus and tubular epithelium has been observed in diabetic renal pathology and is used as a marker of renal tubular injury. It is associated with worsening renal outcomes such as serum Cr, blood urea nitrogen (BUN) and eGFR, and various progressive renal dysfunction .In previous studies , urinaryAlong with the increase in POSTN in the serum of NF patients, the amount of this biomarker also increased in the saliva of these patients, which was not significant in the serum but was significant in saliva. Also, a negative correlation was found between previous years of transplant surgery and salivary and serum POSTN which was not significant.Saliva is a hypotonic solution secreted by salivary glands. The salivary glands are highly permeable, surrounded by numerous blood capillaries, and exchange many molecules, so blood flow biomarkers can be secreted into the saliva . Saliva Therefore, saliva markers will have a high potential for use in routine testing .Because all the confounding factors in the POSTN level have been excluded from this study, the changes observed in this study probably indicate changes in the patient’s kidney.The study focused on patients who passed more than one year of KT surgery. The reason for this criterion is different reasons for transplant rejection during the first year and their long-term survival such as surgical complications, recurrence of primary disease, and immunosuppression. First-year KT patients are very heterogeneous due to their instability. In some studies, this inclusion criterion has not been considered .Also, it should be noted that the weight of POSTN is 90 kDa and will not be removed during dialysis and is, therefore, can measure in these patients.Another study consistent with the present study is a study by Hachim et al. (2020) by bioinformatics analysis. The salivary and serum POSTN of asthmatic patients was examined. In this study, plasma POSTN was upregulated in patients with severe and non-severe asthma. Saliva POSTN was significantly higher in patients with non-severe asthma than in healthy ones and severe asthma patients and these patients were distinguished from each other. The salivary POSTN was also more sensitive than serum POSTN in differentiating severe from non-severe asthma. In this study, as in our study, salivary bio-fluid was the preferred biomarker over serum .ELISA kit used in this study  is for research purposes only and not for diagnostic procedures. The serum, tissue, or salivary POSTN had not been reported in healthy people.According to previous studies, overproduction of TGF_ẞ is one of the stimuli of POSTN secretion from the kidney. Therefore, in dialysis patients, due to the suppression of the inflammatory process caused by failure (secretion of mediators such as TGF_ẞ), the production of POSTN in the kidney is inhibited. According to previous studies, overexpression of POSTN leads to cell proliferation and increased renal fibrosis, which finally leads to reduced renal function. Therefore, it is suggested to re-examine those with very high levels of POSTN .Considering the prevalence of lesions and oral diseases in kidney transplant patients and the significant prevalence of toothache in the group of patients with graft failure, we can mention the importance of the presence of dentists and oral medicine specialists along with other physicians. Based on previous studies and its confirmation in the present study, various oral lesions occur in post-transplant patients, a significant percentage of which can be treated by timely examination and identification. In the center where the present study was conducted, dental and oral health examination and monitoring are performed only before the transplant operation and there is no such monitoring during the post-transplant period. Therefore, this amount of exclusion of the patient does not necessarily happen in other medical centers and patients, especially if the patients are undergoing dental examination. Also it is suggested for future studies investigate the relationship between drug level and oral tissue changes in transplant patients.In addition to considering chronic renal rejection (more than one year), it is suggested to conduct a study to examine POSTN in a group with the rejection of less than one year. In future studies, it is better to examine tissue POSTN along with salivary and serum POSTN. It is also suggested to consider a group of healthy people along with transplant patients.Salivary POSTN in patients with a history of KT could be a marker for the prognosis of renal function. The superiority of saliva as a diagnostic fluid may lead to the replacement of blood with this bio-fluid. The significant results of salivary POSTN may be due to the lack of serum disturbing factors. Saliva is an ultra-filtered fluid from serum and therefore there are fewer proteins and polysaccharides attached to biomarkers in saliva and the accuracy of measuring these biomarkers in the saliva is more valuable than serum.


Objectives: It’s evident that women have a longer life expectancy than men. This study investigates the spatiotemporal trends of gender gaps in life expectancy (GGLE). It demonstrates the spatiotemporal difference of the influence factors of population-weighted air pollution (pwPM2.5) and urbanization on GGLE.Methods: Panel data on GGLE and influencing factors from 134 countries from 1960 to 2018 are collected. The Bayesian spatiotemporal model is performed.Results: The results show an obvious spatial heterogeneity worldwide with a continuously increasing trend of GGLE. Bayesian spatiotemporal regression reveals a significant positive relationship between pwPM2.5, urbanization, and GGLE with the spatial random effects. Further, the regression coefficients present obvious geographic disparities across space worldwide.Conclusion: In sum, social-economic development and air quality improvement should be considered comprehensively in global policy to make a fair chance for both genders to maximize their health gains. The gender differential in longevity has been a subject of interest for scientists. Generally, women have had longer life expectancy (LE) than men, though LE has steadily increased in both sexes during the last decades , 2. Nota2.5), a major component of air pollution, is ranked in the top ten leading global risk factors for disease burdens [2.5 is closely related to a reduction of LE at the country level [Nevertheless, two knowledge gaps should be noted. First, the spatiotemporal trends of GGLE and the regional differences with the geospatial feature are largely unexplored at the global scale. Second, few studies have been performed to comprehensively investigate the environmental and social factors of GGLE and their spatiotemporal difference. For example, fine particulate matter  data for 1998–2016 are collected from the Global Annual PM2.5 Grids data with the spatial resolution of 0.01°×0.01° released by EARTHDATA . We obtained the gridded population of the world at 1,000 m spatial resolution for the year 2005, according to the Socioeconomic Data and Applications Center of NASA (https://sedac.ciesin.columbia.edu/data/collection/gpw-v4). Data on the share of urban population  is from the World Urbanization Prospects: 2018 Revision released by the United Nations Population Division. The data of the poverty gap index is from the Poverty and Inequality Platform by the World Bank, which is based on primary household survey data (https://data.worldbank.org/indicator). Data on the death rate from smoking (both sex with age-standardized) is from the Global Burden of Disease Collaborative Network by the Institute for Health Metrics and Evaluation (IHME) . Data on daily caloric supply is from the Our World in Data (OWID) based on UN FAO & historical sources . Data on education are collected from the database of the UNESCO Institute for Statistics (http://uis.unesco.org/).In this study, the data on life expectancy for females and males in each country from 1960 to 2018 are obtained from the World Development Indicators (WDIs) database published by the World Bank . Furtheri = 1, 2, ..., 134) and year step , the GGLE, yit, was modeled by To model GGLE, a series of Bayesian spatiotemporal models are proposed , where fi-th country or region relative to the global average level, In Eq. and time . The terFurthermore, a Bayesian spatiotemporal ecological regression was developed to investigate the impacts of air pollution and urbanization on GGLE and gender-specific life expectancy while adjusting for confounding factors and spatiotemporal variation. As an extension of model M0s, the variables of PM and UP (two interested variables) were considered, adjusting for confounding factors like poverty (P), education (E), calorie supply (C), and smoking (S). The new model was defined as the following formula (model M1s):2.5, urbanization, poverty, education, supply of calories, and smoking, respectively, measuring the effects of these six variables across 134 overall countries on y . A previous study found that the effects of air pollution and urbanization on LE and gender-specific LE may be spatially varied [2.5 and urbanization on GGLE and gender-specific LE. In this paper, a total of 134 countries are divided into six regions based on the definition of the World Health Organization (WHO) , to investigate the region-specific effects of pwPM2.5 and urbanization on GGLE and gender-specific life expectancy, the modified regression model is shown as follow (model M2s):In Eq. y varied . Model MIn Eq. The average GGLE at the country level and the world is illustrated from 1960 to 2018 . Some keFurther, most countries show a trend from increase to decrease of GGLE with peak values, 41 countries have an increasing trend without a peak value, and only 12 countries/regions show a decreasing trend without a peak value during the study period. The difference is depicted in space, indicating that the countries with increasing or decreasing trends are mainly concentrated in South Asia, Middle Africa, the Middle East, and Latin America . Countrii at time point t is higher than the overall level, while negative values indicate that lower than the overall level. We found that the spatial pattern of GGLE slightly changed from 1960 to 2018. However, the whole spatial pattern is similar at these four-time points. For example, GGLE in Russia is consistently higher than the overall level. In contrast, most countries in Africa have lower GGLE than the overall level. China has a substantial change in GGLE from 1960 to 2018, which indicates a lower level in 1960, 1980, and 2000, but higher levels in 2018 compared to the overall level in the world. Other countries like the U.S., Japan, South Korea, Brazil, Argentina, and South Africa show that GGLE is consistently higher than the overall level.The combined spatial effects of 960–2018 . PositivThe overall temporal trend of GGLE (he world . The GGL2.5 and GGLE, and no significant relations are found between pwPM2.5 and LE in males, and females can be found. Therefore, considering spatial random effects on the global model, the GGLE increased by 0.00034% when a one percent increase in pwPM2.5. Second, urbanization shows a significant positive relation to GGLE with spatial random effects, and significant positive relations are found between urbanization and LE in males and females as well (The global  effects  of GGLE . However of GGLE  indicate as well . Third, 2.5 and urbanization on GGLE and gender-specific life expectancy (2.5 on GGLE can be found in Africa, Eastern Mediterranean, and South-East Asia. A positive effect of pwPM2.5 on GGLE is significant in America, Europe, and Western Pacific. No significant relations between pwPM2.5 and LE in males and females are found in the six regions. Second, our results indicate that the negative effect of urbanization on GGLE can be found in Africa and Europe. In contrast, the positive effect of urbanization on GGLE is significant in America and Eastern Mediterranean. Significant positive relations between urbanization and LE in males and females are found in the six regions.Further, the six WHO regions exhibit geographic disparities in the effects of pwPMpectancy . First, It has been largely unexplored the spatial distribution and variation of GGLE worldwide. The current study is one of the first that exhibited the spatiotemporal trends in GGLE and examined the effects of air pollution and urbanization on GGLE and gender-specific life expectancy from a global perspective. Further, the geographic disparities in the impacts of these influencing factors on GGLE among six WHO regions can be quantified by the regression coefficients by Bayesian spatiotemporal ecological regression. Several key points can be further discussed as follows.First, the spatiotemporal trends in GGLE at the global scale are investigated in this study. Some previous studies have been performed on GGLE’s distribution at the cross-country level. It was found that GGLE grew rapidly during most of the 20th century. Then, a reversal of this trend has been observed that the GGLE has declined since the 1980s among many developed countries such as Italy , France per capita GDP and pwPM2.5 based on the Bayesian regression model [2.5 and urbanization factors as our core independent variables. Using the Bayesian spatiotemporal ecological regression, our findings reveal the significant negative influence of pwPM2.5 and urbanization on GGLE with spatial random effects. Although no significant relations are found between pwPM2.5 and LE in males and females, we reveal the negative regression coefficients in females are lower than in males. In general, our finding is in line with previous studies, which showed that adult males had higher exposure to air pollutant factors than females [Second, it is evident that women have longer LE than men, and female superiority in LE appears to be one of the most striking features of human health –50. Seveon model . This pa females –61. Thus females . Our fin2.5 pollution. Our modeling presents obvious geographic disparities of the impacts of PM2.5 across space. America, Europe, and Western Pacific showed positive relations between pwPM2.5 and GGLE, which is in line with the global trend. Interestingly, these regions exhibit a relatively higher level than the global average. In contrast, Africa, Eastern Mediterranean, and South-East Asia showed the opposite trend, indicating that spatial heterogeneity should be highlighted, especially in the world’s developing regions. Similarly, the spatial heterogeneity of urbanization influence should also be focused on the regions such as Africa, America, Eastern Mediterranean, and Europe. Furthermore, the coupling relationship between urbanization and air pollution has become a hotspot internationally in sustainable development studies [Moreover, our findings could provide several implications. Firstly, the average level and peak values of GGLE show obvious differences among WHO regions in the world, and the countries with higher levels of GGLE are mostly related to higher development levels. It could be inferred that the GGLE may keep increasing with social-economic development and worsening air pollution in most regions worldwide. Secondly, it further indicates that the air pollution factor with spatial autocorrelation should consider the influence of GGLE. Further investigations are needed to probe the gender differences in PM studies . Develop studies . Our fin2.5 exposure data are much needed in the future, the error associated with satellite and simulated PM2.5 concentration was assessed and calibrated in this paper. Similarly, we used the death rate from smoking rather than smoking prevalence as a covariate due to the limitation of data sources, which could be improved in future studies. Secondly, the effect of PM2.5 and urbanization may be biased due to omitted confounders and spatial confounding [2.5 and urbanization indicated that the confounders for GGLE are not the same as for life expectancy. Hence, it may need further analysis of GGLE rather than a comparison of the coefficients between males and females. Fourthly, the collinearity results due to the multi-environmental and social-economic factors should be interpreted with caution in ecological studies [Nevertheless, several limitations and study prospects in this paper should be noted. Firstly, although more accurate human PMfounding . The spafounding . Thirdly studies , especia studies , Human D studies , invest  studies , women’s studies , disease studies , alcohol studies , homicid studies , etc. Fi


This study investigated the effectiveness of tadalafil compared to mirabegron and solifenacin combination therapy in patients with ureteral SRSs after double-J (DJ) stent insertion.this double-blind, randomized clinical trial used consecutive random sampling in participants with SRSs after double-J stent insertion. The study was conducted at four different hospitals in Makassar, Indonesia, from July to December 2020. Ureteral stent-related morbidity indices which analyzed include urinary symptoms, pain, general health, quality of work, and sex scores. All of the indices were measured by ureteral symptom score questionnaire for the first, second, third, and fourth weeks after drug consumption, either tadalafil 10 mg/day  and a combination of mirabegron 25 mg/day and solifenacin 5 mg/day .before the treatment procedure, the groups were comparable in age, gender, body mass index, DJ stent procedures, type, and indication. In general, the score in all parameters declined over the follow-up time for both groups. Group A had a lower urinary symptom score than group B at week III and week IV . In addition, group A had a lower pain score, general condition, work activity, and other complaints than group B at week II, week III, and week IV . The sexual activity score is comparable between the group, except in week I.according to our results, we suggest tadalafil to minimize stent-related urinary symptoms and improve general health in patients with double J stent. A ureteral stent is a tool to facilitate the flow of urine from the kidney to the bladder that is disturbed due to obstruction. Ureteral stents have an important role in the temporary drainage of the upper urinary tract and are a frequently performed procedure in endourological surgery ,2. CurreGiven the large number of patient complaints, a questionnaire system was developed to evaluate morbidity and side effects after DJ stent placement. The Ureteral Stent Symptoms Questionnaire (USSQ) is the gold standard questionnaire to evaluate the morbidity and side effects of post-DJ stent placement. This questionnaire evaluated complaints that asked about urinary complaints, pain degrees, general health status, work activities, sexual activities, and accompanying complaints that cause discomfort on the subject ,5.Along with technological advances and modifications of ureteral stents that continue to be developed to date, various studies to overcome the side effects associated with symptoms after DJ stent placement include modification of stent design, medication, stent position, stent coating, and intravesical therapy ,6,7. Sevet al.found that 8 mg silodosin and 10 mg solifenacin were superior to 5 mg tadalafil [Several previous studies have shown the efficacy of these three drugs in improving SRSs, either single or in combination. Side effects obtained from using this drug are also minimal and well-tolerated -13. Howeadalafil . In addiadalafil . MirabegTrial design: a randomized, double-blind, controlled trial was carried out in the Department of Surgery at Wahidin Sudirohusodo Hospital, University Hospital of Hasanuddin University, Akademis Hospital, and Ibnu Sina Hospital in Makassar City, Indonesia. The trial period was six months, from July 2020 to December 2020.Participants: all patients undergoing unilateral routine DJ stenting after an endourological surgery were enrolled in the study for evaluation. The inclusion criteria are patients with endoscopic indications for insertion of a DJ stent diagnosed with ureteral stones <10 mm , ureteral stenosis and/or kidney stones who underwent shockwave lithotripsy (ESWL), patients who underwent the first installation of a DJ stent, and unilateral DJ stent complained of SRSs on the seventh postoperative day. The exclusion criteria are patients with a history of malignancy in the urinary tract, previous prostate disease, previous sexual dysfunction, previous urinary tract infection (UTI), pregnancy, chronic medical condition , previous or currently undergoing radiation therapy/hormonal therapy and/or minor pelvic surgery procedures, ureteral reconstruction surgery, history of alcoholism, history of stroke, Alzheimer's, central nervous system trauma, comorbid bladder stones, urethral diverticula in women, and hypersensitivity to drugs such as tadalafil, mirabegron, or solifenacin.Interventions: written informed consent regarding the administration and side effects of therapy was signed by the patient. The baseline characteristics were recorded including age, height, weight, and body mass index (BMI). The additional investigation, including urea/creatinine examination, urinalysis, ultrasonography, abdominal radiograph, and computed tomography (CT) scan urography was performed on the patient before surgery. The size of the largest stone from the patient is used as a benchmark to record the size of the patient's stone.All patients who underwent routine post-endurological DJ stent insertion  or ureteroscopic lithotripsy (URSL)) were included in the study evaluation. The DJ stent used with a type of polyurethane double loop  and size of 4.7 Fr was used in all patients with the length of the stent compared to the patient's height.An abdominal radiograph was taken postoperatively to see the remaining stone fragments and the position of the DJ stent. After determining the sample with exclusion and inclusion criteria, the patient will be divided into 2 groups of drug administration. Group A was given tadalafil 10 mg once daily for 1 month and group B was given a combination of mirabegrone 50 mg once daily and solifenacine 5 mg once daily for 1 month.In this study, we did not use the placebo group because there have been many studies comparing the placebo group and the effectiveness of the two drugs, so we took only 2 groups to directly compare the effectiveness of the two drugs. Giving a placebo in this case (the group that was not given the drug) is something that should not be done, considering that the patient has complaints that must be treated so that it does not interfere with the patient’s quality of life.Outcomes: the administration of tadalafil 10 mg/day was compared with the combination of mirabegron 25 mg/day and solifenacin 5 mg/day, starting on the seventh day after the insertion of the DJ stent. The patient will be given the USSQ questionnaire format that will measure the presence or absence of complaints of side effects felt by the patient for 7 days after the installation of the DJ stent. Filling out the USSQ questionnaire started on the seventh day after the insertion of the DJ stent, then it was measured every 7 days  after the insertion of the DJ stent. Filling out the questionnaire can be done by direct interview at the outpatient clinic or by phone. The USSQ include the following: urinary symptom, pain, general health, quality of work, sexual activity, and other symptoms. The patients were told not to take another medicine and should be visited in situations such as fever, severe pain, and discomfort. Consumption of any other drugs, significant complications, or drug cessation were recorded in each visit. The patients were reminded by a physician the day before each visit by phone call.Sample size: the sample size was calculated using the Openepi with a power 1 - β = 0.8, two-tail α = 0.05, and a difference of 2.0 in the mean of USSQ score change at the final follow-up period (week IV). The required sample size was 38 patients with complaints of SRSs after DJ stent insertion (19 samples in each group). Considering a 30% of dropout and failure to consent, 25 participants in each group are needed.Randomization and blinding procedure: subjects were divided into two groups, each group of 25 patients was simply randomly assigned to treatment (1: 1 ratio). The double-blinded method was used to minimize bias. All medicines were placed in the same 2 boxes, which were held by paramedics, so that patients and researchers did not know the allocation of the type of drug given. All patients have been informed about the side effects of the drug.Statistical analysis: the data was coded, entered, and analyzed using the Ms. Excel 2010, and the statistical analysis used was Statistical Package for the Social Science  software. Quantitative data including the age, body mass index (BMI), and USSQ scores were presented in the form of mean and standard deviation. The independent t-test was conducted to compare the USSQ score at each time of follow-up between the two groups. The paired t-test was conducted to compare the USSQ score between week I and week IV measurements in the two groups. The categorical data was presented in percent and compared between groups using the chi-square test or Fisher exact test. P-value < 0.05 was considered statistically significant. The analyzed data was presented in the form of frequency tables and cross-tabulation tables, graphs, and narratives for interpretation and discussion.Ethics: this study was carried out after was approved by the Health Research Ethics Committee, Faculty of Medicine, Hasanuddin University Makassar (No. 301/UN4.6.4.5.31/PP36/2021). Before being enrolled in the study, participants received information and were required to sign a written agreement. The collected information was private and anonymous. The randomized clinical trial (RCT) registration number was researchregistry7127 on September 6, 2021.Participants flow:Baseline data:2vs 22.83 ± 3.47 kg/m2, p=0,048). However, both groups had comparable baseline characteristics in other parameters .Comparison of USSQ scores in both groups after DJ stent insertion: each subject was included in two groups of observations according to effectiveness comparisons between the two observed pharmacotherapy . There was no significant difference in the first two weeks, but the two groups tested showed clinical improvement in four weeks of therapy . The P score was lower in the tadalafil group than in the mirabegron + solifenacin group at weeks II, III, and IV . There was no significant difference in the first weeks, but the two groups tested showed clinical improvement in four therapy weeks .The GC scores were lower in the tadalafil group than in the mirabegron + solifenacin group in the follow-up period. However, the GC scores were significantly lower in the tadalafil group than in the mirabegron + solifenacin group only at weeks II, III, and IV . Both groups showed a significant decrease in the GC score, indicating the clinical improvement felt by the patient after undergoing therapy for one month .The WA scores were significantly lower in the tadalafil group than in the mirabegron + solifenacin group in the entire follow-up period , except at week I . Both groups significantly decreased the WA score at the last follow-up period . The S scores were significantly higher in the tadalafil group than in the mirabegron + solifenacin group at week I  but significantly lower at week IV . However, the S scores had comparable means in both groups at week II and week III . Interestingly, the S scores tend to lower during the follow-up period in the tadalafil group . Contrarily, the S scores tend to be higher during the follow-up period in the mirabegron + solifenacin group . Some of the samples in this study were sexually inactive, such as not having a partner or old age, and the timing of resumption of sexual activity was uneven, so the researchers could not confirm whether there were other external factors associated with this difference in scores, but the scores were statistically significant.The OC scores constitute the following item: perception of urinary tract infections, sense to consume additional antibiotics, necessity for medical assistance for catheter care, necessity for hospital admission, and perception of happiness in reinserting the DJ stent. The OC scores were significantly lower in the tadalafil group than in the mirabegron + solifenacin group at weeks II, III, and IV , except week I (p=0.061). Both groups showed a significant decrease in the OC scores indicating the clinical improvement felt by the patient after undergoing therapy for one month .et al. investigation of the advantages and risks of inserting DJ stents in Pakistan, which assessed 80 patients who had stents. The study indicates that, with a male-to-female ratio of 2.6: 1, most patients (40.0%) ranged in age from 36 to 50 [This study revealed that male patients comprised more than 70% of the occurrence in both group and the majority (52.84%) in the age of 26-45 years. The findings of this study are comparable with those of Pansota 36 to 50 .Post-DJ-stent patients who experienced SRSs were divided into 2 groups and treated with Tadalafil 10 mg/day or a combination of mirabegron 25 mg/day + solifenacin 5 mg/day. Both groups were then observed and assessed using the USSQ questionnaire. According to the study's findings, the tadalafil therapy group exceeded the mirabegron and solifenacin combination group in treating all SRSs.et al. who assessed 40 patients who were given tadalafil 10 mg/day and found that it significantly decreased lower urinary tract symptoms, pain, sexual function, and the overall score associated with stents [et al. in a study including 72 patients who received tadalafil 10 mg/day from day 7 to day 21. This treatment significantly decreased pain and improved overall health, performance, and sexuality index ratings. In addition, this treatment can reduce lower urinary tract symptoms and enhance patient quality of life [The findings of this study suggest that treatment with tadalafil 10 mg/day for three weeks in patients having DJ-stents implanted can lessen complaints of urinary symptoms, pain, complaints of general condition, complaints of working activity, complaints of sexual activity, and other complaints. The most effective treatment for patients following DJ-stent insertion can reduce pain complaints using tadalafil 10 mg/day for three weeks. The findings of this study are consistent with those of Haghro h stents . Similar of life .et al. using the USSQ scores. They found that urinary symptoms can reduce by 18.07 ± 8.10 points in three weeks of treatment with tadalafil 5 mg. Other parameters were significantly reduced, including pain, general condition, working activity, sexual activity, and other complaints. However, the improvement in pain scores, general condition scores, and other complaints scores were higher in the present study than the previous results in Bhattar et al. study . The higher dosage in the present study may explain the difference in results between this study. Contrarily, the improvement of the working activity and sexual activity in the present study were lower than in Bhattar et al. study  [Tadalafil 10 mg in this study can reduce urinary symptoms by 19.08 ± 4.21 points in three weeks. Similar findings were also reported by Bhattar et al. who compared the combination of mirebegron and solifenacin with monotherapy  and placebo in patients suffering from overactive bladder (OAB), found that patients receiving combination therapy had better urinary complaints than the monotherapy and placebo group [et al. (2017) by collecting data on 435 sites in 42 countries also compared the combination of mirebegron and solifenacin with monotherapy  and placebo in patients suffering from OAB, obtained superior results under combination therapy compared to monotherapy [Similar to the efficacy of tadalafil in the present study, the combination of mirabegron 25 mg/day + solifenacin 5 mg/day for three weeks can improve the urinary symptoms, pain, general condition, working activity, and other complaints. However, there was a significant in allegations of sex activity. In a study conducted by Abrams bo group . Anotherotherapy .Based on previous studies, researchers have not found a study comparing the effectiveness of tadalafil 10 mg/day and the combination of mirabegron 25 mg/day + solifenacin 5 mg/day in patients with SRSs. The limitations of this study were that some of the samples in this study were sexually inactive such as not having a partner, old age, and a partner died, as well as the uneven timing of starting sexual activity so that it affected the results on the USSQ questionnaire and the duration of observation in this study lasted for 4 weeks so that only can assess the short-term effect of drug administration on complaints of SRSs. There are other several limitations such as a small sample size, and no comparison after stent removal. The variations and bias in the USSQ questionnaire's five parts have a logical correlation to each other; for example, the patients who had stent-related urinary symptoms have more chance for sexual dysfunction, and the patients who had urinary symptoms, pain, and inappropriate general health had bad quality and quantity of job.Tadalafil and a combination of mirabegron and solifenacin improved the SRSs in three weeks. However, additional benefits can be achieved using tadalafil 10 mg. This may imply the single use of tadalafil 10 mg in overcoming SRSs is more considered than the combination therapy, particularly in patients with drug compliance problems. There is a need for further research on the effectiveness of single groups and combination groups with more varied types and doses of drugs, screening for more specific sample characteristics so that the results of the questionnaire conducted can be more homogeneous, and observations with a larger number of samples and a more extended study period to determine short-term and long-term effects and evaluation in therapy in this study.Modification of stent design, stent position, stent coating, and intravesical therapy have overcome the side effects associated with symptoms after DJ stent placement;Various medications have overcome the side effects associated with symptoms after DJ stent placement.The superiority of tadalafil 10 mg/day compared to mirabegron 25 mg/day and solifenacin 5 mg/day combination in overcoming almost all complaints of Stent Related Symptoms (SRSs);The effectivity of taladafil 10 mg/day did not differ significantly from mirabegron 25 mg/day and solifenacin 5 mg/day combination in overcoming sexual dysfunction.