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Endogenous microbiome pathway activity patterns influence the colonisation efficiency of PDB | To investigate whether variations in the FMM data were associated with the highly variable and subject-specific relative abundance of PDB during the intervention periods, RDA analysis was performed using the FMM determined during the intervention periods and, as explanatory variable, the average relative abundance of PDB during their respective interventions (Fig. Small intestinal microbiota activity associates with the temporary colonisation by PDB. Taken together, our results highlight how the endogenous microbiota composition and its predominantly active energy metabolism could explain the individual-specific PDB colonisation efficiency, specifically identifying the | PMC9990280 |
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Discussion | stoma | In this study, we present the longitudinal metataxonomic study of the small intestine microbiota, including diet intervention periods to assess the microbial impact of the consumption of bacteria-rich fermented dairy products. Although metataxonomic analysis was the focus of this study, we also determined whether the interventions affected small intestinal mucosal permeability or the SCFA composition of the stoma effluent, revealing that neither of these parameters was significantly affected during the dairy product interventions. Nevertheless, the SCFA measurements confirmed previous observations that substantial amounts of microbial fermentation end-products are already formed in the small intestine [Our metataxonomic results confirmed the previously reported high degree of difference of the small intestinal microbial composition between and within subjects [We expanded the metataxonomic analysis in this study with metatranscriptome analysis of the small intestine microbiota at the start and end of each of the intervention periods, using genome mapping and FMM analysis to determine the activity profile of the small intestine microbiome. Notably, comparative analysis of the metatranscriptome FMM patterns also showed that the individual from which the sample was taken was the co-variate that explained most of the observed variance in FMM (~ 25%). Nevertheless, the intervention period could explain approximately 5% of the total FMM variance, identifying the activation of the The striking variation in subject-specific relative abundance of the PDB allowed a stratified interpretation of the metataxonomic data, identifying the strong association of the abundance of the | PMC9990280 |
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Conclusions | This study shows that the consumption of milk products fermented by | PMC9990280 |
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Acknowledgements | We would like to thank the Host-Microbe Interactomics group of Wageningen University and the team of Danone Research for the fruitful discussions about the results obtained. We are also grateful to dr.ir. Peter van Baarlen for the excellent inputs, support and discussion. | PMC9990280 |
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Authors’ contributions | Edoardo Zaccaria Tim Klaassen and Annick M.E. Alleleyn are co-first authors; Michiel Kleerebezem and Freddy J. Troost are co-last authors. Study concept and design: Michiel Kleerebezem, Freddy J. Troost, Tamara Smokvina. Acquisition of data: Tim Klaassen, Annick M.E. Alleleyn, Edoardo Zaccaria, Freddy J. Troost. Analysis and interpretation of data: Edoardo Zaccaria, Michiel Kleerebezem, Freddy J. Troost. Drafting of the manuscript: Edoardo Zaccaria, Michiel Kleerebezem, Freddy J. Troost, Tim Klaassen. Critical revision of the manuscript for important intellectual content: Michiel Kleerebezem, Freddy J. Troost, Tamara Smokvina. Statistical analysis: Edoardo Zaccaria, Jos Boekhorst, Tim Klaassen. Obtained funding: Michiel Kleerebezem, Freddy J. Troost. Administrative, technical, or material support: Freddy J. Troost, Michiel Kleerebezem. Study supervision: Michiel Kleerebezem, Freddy J. Troost. The authors read and approved the final manuscript. | PMC9990280 |
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Funding | This study was funded by Danone Research via an investigator grant (code: INSIDE:PLF-8712-GD). Study sponsor was not involved in the study design and in the collection, analysis, and interpretation of data nor in the decision to submit this work for publication. | PMC9990280 |
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Availability of data and materials | The datasets supporting the conclusions of this article are available in the DANS repository, on the following doi: 16S 10.17026/dans-xhw-dhpr, Metatranscriptome 10.17026/dans-xvh-yww8, Permeability test 10.17026/dans-xnp-nkq8, Urine Metabolites: 10.17026/dans-2ad-cx47, Short Chain Fatty Acid profiling 10.17026/dans-z3q-vvz4. The supplementary | PMC9990280 |
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Declarations | PMC9990280 |
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Ethics approval and consent to participate | This study was approved by the Medical Ethics Committee of Maastricht University (MU), Maastricht, the Netherlands, and performed in full accordance with the Declaration of Helsinki (latest amendment by the World Medic Association in Fortaleza, Brazil, in 2013) and Dutch Regulations on Medical Research involving Human Subjects (WMO, 1998), as well as with the International Conference on Harmonisation–Good Clinical Practice (ICH-GCP) guidelines. The study was performed at MU from October 27th, 2016 (screening visit, first subject) until October 27th, 2017 (last visit last subject). This study was registered in the US National Library of Medicine ( | PMC9990280 |
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Consent for publication | Not applicable. | PMC9990280 |
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Competing interests | This author discloses the following: T. Smokvina is an employee of Danone Research. The remaining authors declare that they have no competing interests. | PMC9990280 |
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References | PMC9990280 |
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Methods | We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18–33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. | PMC10637674 |
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Results | STIS | There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, | PMC10637674 |
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Conclusions | STIS | Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies. | PMC10637674 |
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Data Availability | The data that support the findings of this study are available in Table S5. | PMC10637674 |
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Introduction | STIS, SEXUALLY TRANSMITTED INFECTIONS | Sexually transmitted infections (STI) continue to be a global health concern. Most STIs are asymptomatic, often undetected and are therefore left untreated [Multiple behavioral and social factors increase STI risk among young women including inconsistent or lack of condom use, multiple sexual partners [The aim of the study was to investigate the prevalence and incidence of STIs among South African women and to compare incidence between contraceptive arms, age groups, study sites, and according to condom use and semen detection. | PMC10637674 |
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Methods | PMC10637674 |
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Study participants | The participants in this sub-study were enrolled at the Setshaba Research Centre (SRC) in Tshwane (n = 53) and MatCH Research Unit (MRU) in eThekwini (n = 109) as part of the ECHO trial [ | PMC10637674 |
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Specimen collection and processing | PROSTATE | For this sub-study, lateral vaginal wall swab samples were collected between June and December 2017 for STI diagnosis and prostate specific antigen (PSA), a biomarker of semen, testing. Specimens were collected at three timepoints—at baseline (immediately before contraceptive method initiation), month one (M1), and month three (M3). Almost all (96%) participants completed all three visits. Samples were collected by placing Dacron swabs on the lateral vaginal wall and rotating 360 degrees, prior to storage at -80°C for a median time of 23 months (range 21–28 months).Frozen lateral vaginal wall swabs were thawed on ice overnight at 4⁰C prior to elution in 1 mL of phosphate buffered saline (PBS; Sigma-Aldrich, P5493). Tubes were vortexed for 60 seconds and incubated at 4⁰C for 1 hour. Excess mucus was then scraped off the inner wall of the tubes and each tube was vortexed again for 30 seconds. | PMC10637674 |
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STI testing | HSV-2 | All participants were tested for CT and NG using a nucleic acid amplification test on the GeneXpert instrument system at screening, the final visit and as clinically indicated in the ECHO trial. Additionally, HSV-2 serologic testing was conducted at screening and final visits as part of the parent trial at Bio Analytical Research Corporation South Africa [ | PMC10637674 |
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PSA measurement | ® | Swab eluants were transferred into filter centrifuge tubes (Corning® Costar® Spin-X® tubes Sigma-Aldrich, | PMC10637674 |
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Data analysis | Statistical analyses were performed using GraphPad Prism (GraphPad Software, USA) and R Studio (R Studio Software, USA). Women were grouped by age to include approximately equal numbers within each group (18–21; 22–25; 26–33 years). We used the Fisher exact test to compare baseline STI prevalence between groups, including age group, contraceptive group (copper-IUD, LNG implant and DMPA-IM) and Chi-Square test for PSA detection (detected/not detected), condom use (yes/no) and site (eThekwini/Tshwane). Kruskal-Wallis test was used to compare weight, height, body mass index and number of sex acts in the past three months. We compared STI incidence over the three-month follow-up period between groups using the Kaplan-Meier method. P-values were adjusted for multiple testing using a Bonferroni correction [ | PMC10637674 |
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Results | PMC10637674 |
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Cohort characteristics | Baseline demographic, behavioural and clinical characteristics of the study participants are described by age group ( | PMC10637674 |
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Baseline STI prevalence | HSV-2 | STI prevalence was high overall, with 40% of women having an active STI (CT, NG, TV, MG or HSV-2 shedding), 10% having more than one STI, 19% having CT and 19% having TV ( | PMC10637674 |
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Total proportion of women with active sexually transmitted infections (STIs) at baseline by age group. | STI infections | The younger (18–21, n = 52) and middle (22–25, n = 62) age group had a greater proportion of STI infections than the older age group (26–33, n = 47). The younger age group had a greater proportion of | PMC10637674 |
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Baseline STI prevalence overall and by age group. | Abbreviations: STI, sexually transmitted infection.^tested positive for at least one STI (CT, NG, TV, MG or HSV-2). Proportions were compared using the Fishers Exact test*p<0.05 following Bonferroni correction was considered statistically significant. | PMC10637674 |
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STI incidence | STIS, EVENT, SEXUALLY TRANSMITTED INFECTION | The incidence of any active STI during the three-month follow-up period was very high [107.9/100 women years (wy); (A-F), Kaplan-Meier curve showing sexually transmitted infection (STI) incidence between age groups over time (days). Red represents the 18–21 year olds, green the 22–25 year olds and blue the 26–33 year olds. The tables show the number of individuals at risk of acquiring STIs over time. A vertical drop represents an event has occurred and a verticle tick mark on the curves indicate that a participant has been censored at that timepoint. (A) Any STI incidence over time. There were no significant differences between any age groups. (B) | PMC10637674 |
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Three-month STI incidence overall and by contraceptive group. | *p<0.05 following Bonferroni correction was considered statistically significant.No statistically significant differences in STI incidence between contraceptive groups was noted, but trends towards higher incidence of any active STI or CT alone were observed in the DMPA-IM arm compared to LNG implant users (p = 0.11 and p = 0.07, respectively; | PMC10637674 |
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Discussion | HIV, adverse pregnancy outcomes and infertility, infection, infections, HIV infection | STIS, INFECTION, INFECTIONS, HIV INFECTION | STIs have a major impact on both sexual and reproductive health and, in addition to their individual pathogenic effects, increase the risk of HIV, adverse pregnancy outcomes and infertility. Understanding factors that influence STI prevalence and incidence is critical for the implementation of effective management strategies to reduce the burden of these infections and associated adverse outcomes. Similar to previous studies [Younger women (18–21 years) had a higher prevalence of CT compared to older women (26–33 years), 29% vs 8% respectively. This is similar to the prevalence reported in the ECHO parent study that recorded CT prevalence of 20–28% in South African women at baseline and found that younger women were more likely to have a CT infection than older women [We measured PSA as a biomarker of semen to evaluate the relationships between recent unprotected sexual intercourse, reported condom use and STI incidence. Only 13% of individuals tested positive for PSA at baseline and, while PSA was not associated with reported condom use, it was significantly associated with reporting of recent vaginal sexual acts. We did not find any association between PSA positivity across all visits and STI incidence, and we did not observe significant differences in PSA detection between age groups, study sites or contraceptive arms. However, a study by Deese et al. [This study had several important strengths including randomization to contraceptive method, high adherence to contraceptive method and testing for STIs and other co-factors. However, limitations include the small sample size, short follow-up period, and limited power to evaluate differences between some of the STIs between the different groups. It would also be vital to study the STI incidence and prevalence rates in women living with HIV as this cohort included only seronegative women. This has importance as previous studies have reported a bidirectional relationship between HIV and STIs, with women with HIV more likely to have a STI compared to HIV-negative women [In conclusion, this study found a high prevalence and incidence of STIs, especially in young women who are also most at risk of HIV infection in South Africa [ | PMC10637674 |
Supporting information | PMC10637674 |
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Inclusivity in global research. | (DOCX)Click here for additional data file. | PMC10637674 |
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Total proportion of women with active sexually transmitted infections (STIs) at baseline by study site. | STIS, EVENT, SEXUALLY TRANSMITTED INFECTION | The Setshaba (n = 53) study site had a greater proportion of (JPG)Click here for additional data file.(A-C). Kaplan-Meier curve showing sexually transmitted infection (STI) incidence between study site by age group over time (days). Red represents the MatCH site, green the Setshaba site. The tables show the number of individuals at risk of acquiring STIs over time. A vertical drop represents an event has occurred and a verticle tick mark on the curves indicate that a participant has been censored at that timepoint. (A), STI incidence between sites for 18–21 year olds were not statistically significant. (B), There was no statistically significant differences for 25–33 years olds between sites. (C), STI incidence between sites for 26–33 year olds had a statistically significant difference (p = 0.002).(JPG)Click here for additional data file. | PMC10637674 |
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Kaplan-Meier curve showing any active sexually transmitted infection (STI) incidence between participants testing positive or negative for vaginal prostate specific antigen (PSA). | EVENT | Red represents participants positive for PSA at any visit, green indicates participants negative for PSA at all visits. The tables show the number of individuals at risk of acquiring any active STI over time. A vertical drop represents an event has occurred and a cross mark on the curves indicates that a participant has been censored at that timepoint. There was no statistically significant difference in the incidence of an active STI between participants positive or negative for PSA.(JPG)Click here for additional data file. | PMC10637674 |
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Total proportion of women reporting ever using condoms according to prostate specific antigen (PSA) detection at baseline. | There were no significant differences in PSA detection in women who reported condom use and in women reporting no condom usage.(JPG)Click here for additional data file. | PMC10637674 |
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Vaginal prostate specific antigen (PSA) concentrations according to reported time since last vaginal intercourse (days). | PSA concentration was significantly higher among women reporting vaginal intercourse 0–4 days compared to 8–13 days prior to the study visit (p = 0.03).(JPG)Click here for additional data file. | PMC10637674 |
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Baseline demographic, behavioural and clinical characteristics of study by study site. | Abbreviations: (DOCX)Click here for additional data file. | PMC10637674 |
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Baseline STI prevalence overall and by study site. | SEXUALLY TRANSMITTED INFECTION | Abbreviations: STI, sexually transmitted infection. ^tested positive for at least one STI (CT, NG, TV, MG or HSV-2). Proportions were compared using the Fishers Exact test *p<0.05 following Bonferroni correction was considered statistically significant.(DOCX)Click here for additional data file. | PMC10637674 |
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Baseline STI prevalence overall and by contraceptive group. | SEXUALLY TRANSMITTED INFECTION | Abbreviations: STI, sexually transmitted infection. ^tested positive for at least one STI (CT, NG, TV, MG or HSV-2). Proportions were compared using the Fishers Exact test *p<0.05 following Bonferroni correction was considered statistically significant.(DOCX)Click here for additional data file. | PMC10637674 |
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Three-month STI incidence overall and by study site. | *p<0.05 following Bonferroni correction was considered statistically significant.(DOCX)Click here for additional data file. | PMC10637674 |
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Full study dataset. | (XLSX)Click here for additional data file.We thank all the women who participated in this study, the communities that supported this work and the study teams responsible for the collection, processing, storage and shipping of the samples. The contents of this paper are solely the responsibility of the authors and do not necessarily reflect the views, decisions, or policies of the institutions with which they are affiliated, the ECHO trial funders, or the supporting governments. | PMC10637674 |
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Introduction | death | DISEASE PROGRESSION | Transgender women (TGW) remain a key population within the global HIV pandemic, with estimates that suggest that their risk of acquiring HIV is almost 50 times higher than the rest of the population [Treatment-related factors may also affect the level of adherence to antiretroviral treatment (ART). Complexity of regimen (dosing frequency, pill burden) and presence of side effects are frequent correlates of treatment abandonment [Increasing TGW’s ART adherence and retention is critical for this population’s quality of life and for public health. Evidence demonstrates that provision of HIV treatment, in addition to preventing disease progression and death, greatly reduces transmission to sex partners, an approach known as treatment as prevention (TasP) [We, therefore, hypothesized that a DTG-based treatment would be an effective regimen in ART-naïve, HIV-1-infected TGW. We conducted this 48-week study to determine retention, adherence and viral suppression of TGW treated with DTG plus tenofovir disoproxil fumarate (TDF) coformulated with either emtricitabine (FTC) or lamivudine (3TC) (DTG + TDF-XTC) and to identify clinical and psychosocial factors associated with retention. | PMC9858466 |
Methods | PMC9858466 |
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Study setting | ’ | This study was conducted in a non-governmental organization that provides free-of-charge trans-competent and trans-affirmative HIV care in the context of clinical research in Buenos Aires, Argentina. Our trans-affirmative healthcare service includes a) use of patients’ preferred name and pronoun in interactions, clinical records and forms (which include sex assigned at birth and gender identity); b) an interdisciplinary trans-competent trained staff, aware of transgender people’s needs and accepting of their identities; c) integration of multiple services for this community (e.g., HIV, gender-affirming medical procedures, anal health) to simplify service delivery; d) adjustment to transgender populations’ social contexts (e.g., flexible scheduling and hours); and e) inclusion of transgender peer navigators. Peer navigators function as a bridge between the research site and the transgender community. Some of their main tasks are: a) to provide health information to their peers adapting it to their community and making it more accessible and comprehensible, b) to invite potential participants and to enroll them in the studies, c) to verify that they understood the informed consent correctly and to answer any concern about it, d) to assist transgender people in obtaining medical appointments and in navigating the healthcare service, e) to remind participants their upcoming visits, and f) to contact lost to follow-up participants to re-engage them in the study. | PMC9858466 |
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Study design | MAY | This was a prospective, open-label, single-arm trial of DTG-TDF/XTC. This study was designed in a national context of use of efavirenz-containing triple antiretroviral regimen with possible changes in sleep quality. This regimen could particularly affect a population with high proportions of engagement in nightly sex work, such as TGW [Participants were recruited by outreach efforts of peer navigators, through testing campaigns conducted in places were transgender people gather or live, and through collaboration with a local transgender community-based organization. Eligible participants started ART and were followed for 48 weeks according to study protocol and procedures, between December, 2015 and May, 2019 ( | PMC9858466 |
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Statistical analyses | SECONDARY, EVENT | Sample size was not determined in advance and a convenience sampling was conducted. All data were anonymized and analyzed using the Statistical Package for the Social Sciences (SPSS) 24 software.Descriptive statistics were presented for the primary and secondary outcomes, with median and interquartile ranges (IQRs) or frequencies and proportions (%), as appropriate. Comparisons between “retained” and “not retained” individuals were performed to identify baseline clinical and sociodemographic factors associated with loss of follow-up at week 48, using Chi-square/Fisher’s exact test for categorical variables, and Mann-Whitney’s U test for continuous variables when normality was not confirmed. Longitudinal differences between baseline and week 48 were assessed for CD4 count and weight, using Wilcoxon rank-sum test, as these variables showed non-normal distributions. A survival analysis of retained participants was performed with R (survival package). Time to event was calculated by Kaplan-Meier method. For all the analyses, a | PMC9858466 |
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Ethics statement | TransViiV study was evaluated and approved by the institutional review board under the number FH-17. The study was carried out following the good clinical practices. All individuals provided a written informed consent before participation in any study procedure. Participation was voluntary. At each visit, participants received a $150 Argentine pesos compensation (approximately, 15 USD at the moment of the study) to cover transportation costs, and a coupon exchangeable for a basic breakfast or meal. | PMC9858466 |
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Results | MAY | Between December, 2015 and May, 2018, 75 TGW were screened. Of these, 61 were enrolled and received the study treatment. Fourteen TGW (18%) were considered screening failure, being the most frequent reasons non-amplification of the genotypic test and plans to move to another city in the following year ( | PMC9858466 |
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Screening to week 48. | NOTE. | PMC9858466 |
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Baseline clinical and psychosocial characteristics | At enrollment, most patients were asymptomatic, with 96% CDC staged as class A. Main HIV route of transmission was unprotected sexual contact. Within the baseline clinical characteristics ( | PMC9858466 |
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Baseline characteristics of enrolled, retained, and virally suppressed HIV positive TGW. | ideation, drug abuse | Abbreviations: IQR, interquartile; pVL, plasma viral loadBaseline psychosocial characteristics show high levels of social vulnerability (e.g., 53% [n = 32] reported unstable housing; 77% [n = 47], current engagement in sex work; 61% [n = 37], incomplete high school education). Regarding mental health indicators, 26% (n = 16) of these TGW reported significant suicidal ideation in the last 2 weeks. Moreover, 66% reported drug use in the last year (53% [n = 32] reported cocaine use), 13% [n = 8] evidenced possible drug abuse and 53% (n = 32) presented hazardous alcohol use. | PMC9858466 |
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Adherence, retention and viral suppression | Regarding adherence, the mean for week 24 was 86.9% and the median value was 95% (76.6–95). For week 48, the mean reported adherence was 86.3% and the median value was also 95% (76.6–95).Regarding retention, 82% were retained in the study at week 24 and this proportion decreased to 77% at week 48. Of the 47 retained participants, 2 did not have a pVL at week 48 but, as they attended the clinic, they were considered as retained for the analyses. Although 14 (22%) participants were discontinued or lost to follow-up (In relation to the CD4 count, a statistically significant increase was recorded between baseline and week 48 ( | PMC9858466 |
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Survival analysis | EVENT | The starting point for this analysis is baseline visit when participants received the first treatment medication. Time between this visit and the next medication dispensed (next visit date) was calculated until the first event of no medication dispensed occurred. When this happened, the participant was considered “not retained in the study” for that time point. The survival analysis performed shows that the probability of retention in the study decreases with time ( | PMC9858466 |
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Time to last visit/medication dispensed curve. | PMC9858466 |
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Safety and tolerability | death, Hypertriglyceridemia, cryptococcal meningitis, weight gain, appendicitis | HYPERTRIGLYCERIDEMIA, CRYPTOCOCCAL MENINGITIS, APPENDICITIS, MENINGEAL TUBERCULOSIS, INTESTINAL TUBERCULOSIS | The study drugs were well tolerated. Nine clinical AEs (grade 1: 17% [8/47] and grade 2: 2% [1/47]) were classified as possibly related to study treatment. The most frequent laboratory abnormalities were elevated aspartate transaminase/alanine transaminase (grade 2: 20% [9/45]) without an increase in bilirubin. Hypertriglyceridemia (grade 2) was observed in 13.3% (6/45) of the participants.Five participants presented SAEs, although none were considered related to study treatment, and two resulted in the participant’s discontinuation from the study (one was a suicide attempt after 8 weeks of treatment and the other, a meningeal tuberculosis at week 4, leading to death). Although external factors were identified in the case of suicidal attempt, after discussing with the medical team, it was decided to discontinue ART. The other 3 SAEs included cryptococcal meningitis at day 5, intestinal tuberculosis at week 20, and appendicitis at week 24 that resulted in hospital admission. These three participants finalized the protocol.Given that weight gain has been reported for DTG-based regimens, changes at week 48 were analyzed for exploratory reasons. Participants increased their weight, on average, by 2.6% compared to their weight at the baseline visit. In absolute terms, there was an increase of 1.5 kilos on average between baseline and week 48; this difference was not statistically significant ( | PMC9858466 |
Clinical and psychosocial factors associated with retention | As shown in | PMC9858466 |
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Baseline clinical and psychosocial characteristics by retention status among HIV positive TGW. | * ** Fisher’s exact test is recorded. | PMC9858466 |
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Discussion | toxicity, weight gain | This study with HIV-1-infected ART-naïve TGW showed that 77% met the protocol definition of retention (at week 48) after their initial prescription of drug regimen comprising DTG plus TDF-FTC or 3TC. Likewise, 72% and 97% of participants showed viral suppression at week 48 in ITT and per-protocol analyses, respectively. The regimen had low toxicity, good tolerance and high adherence (about 95%).Although retention and viral suppression figures are below the UNAIDS recommended goals, they still represent an achievement in this challenging group of patients. In fact, studies from Latin America show lower rates of retention among TGW. A respondent-driven sampling study among TGW in Brazil that aimed to estimate the HIV cascade of continuum of care showed that 67.2% reported linkage to care [Baseline characteristics of the sample show a high level of psychosocial vulnerability. One third of the participants (30%) were foreign-born, half of them reported unstable housing, and a high proportion was engaged in sex work for a living. These factors, among others, may increase mobility and, therefore, the risk of being lost to follow-up in HIV care [Age was one of the factors associated with retention in this sample of TGW. Older TGW are more likely to be retained in the study than younger ones. In relation to this, older TGW may have a history of approaching the healthcare system seeking gender-affirming medical procedures (e.g., hormone therapy), which then facilitates access to other healthcare services that they may need, such as HIV care [Adherence to ART is affected by a range of factors, among them, the AEs associated with chronic therapy [The absence of a control arm did not allow us to draw conclusions about efficacy of once-daily DTG-based ARV-naïve patients. However, in this single-arm study, this regimen achieved viral suppression in 72% of 45 patients by ITT analysis and 97% in the analysis per-protocol. Given that the number of “non-suppressed” participants was very small, an exploratory analysis of possible correlates of this condition could not be conducted, as required statistical parameters were not achieved.In the course of DTG-based ART, an unexpected excess in weight gain has been reported [In Argentina, gender identity stigma from healthcare workers is associated with avoidance of TGW to attend healthcare services [ | PMC9858466 |
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Limitations | STILL | The present study has some limitations. Firstly, our findings cannot be generalized to all HIV positive TGW in Argentina. A small non-probability sample was enrolled, limiting generalizability of results. Still, the final sample showed sociodemographic characteristics that are similar to nationwide studies with non-clinical samples [Although our results seem favorable in the context of this specific population, they are still far from the achievement of the UNAIDS global 95-95-95 HIV goals by 2030 [ | PMC9858466 |
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Conclusion | In this study, DTG-based treatment delivered by a trans-competent team in a trans-affirmative service was safe and well tolerated by TGW and associated with high retention, high adherence and high viral suppression at 48 weeks among those being retained. Thus, results support the use of DTG-based treatments in this population, as it is recommended by the WHO [Despite involving a small sample of TGW, this is the first longitudinal study of these characteristics in Argentina, contributing to the scarce information available in Latin America, on retention and adherence to ART among transgender people. It also supports the need for a more comprehensive approach in HIV care, integrating medical and psychosocial/behavioral factors, to address retention in this population. As these results suggest, a trans-affirmative approach in care and the inclusion of peer navigators may facilitate access to healthcare and favor greater retention. Thus, it is recommended to continue exploring the feasibility of the implementation of these strategies in public healthcare services. | PMC9858466 |
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Supporting information | PMC9858466 |
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Original protocol Spanish version. | (PDF)Click here for additional data file. | PMC9858466 |
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Original protocol English version. | (PDF)Click here for additional data file. | PMC9858466 |
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Minimal anonymized data set. | Travestis | (XLSX)Click here for additional data file.The authors would like to thank all the participants and organizations that work with us, and that collaborate in improving the health of the trans population: Asociación de Travestis, Transexuales y Transgéneros de Argentina (A.T.T.T.A), Asociación Civil Hotel Gondolin and Casa Trans. | PMC9858466 |
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Background and purpose | aneurysms, intracranial aneurysms | ANEURYSMS, INTRACRANIAL ANEURYSMS | The CATCH (Coil Application Trial in China) trial was designed to assess the safety and efficacy of the Numen Coil Embolization System in the treatment of intracranial aneurysms in comparison with the Axium coil (ev3/Medtronic). Although the endovascular treatment of small (< 5 mm) intracranial aneurysms has been reported with favorable long-term clinical and angiographic outcomes, randomized trials are still lacking. Data for aneurysms smaller than 5 mm were extracted from the CATCH trial. | PMC10276443 |
Materials and methods | aneurysm occlusion, intracranial aneurysms | SECONDARY, RECURRENCE, INTRACRANIAL ANEURYSMS | A randomized, prospective, multicenter trial was conducted at ten centers throughout China. Enrolled subjects with small intracranial aneurysms were randomly assigned to receive treatment with the Numen Coil or the Axium coil. The primary outcome was successful aneurysm occlusion at the 6-month follow-up. In contrast, the secondary outcomes included complete aneurysm occlusion, recurrence rate, clinical deterioration, and safety data at the 6-month and 12-month follow-ups. | PMC10276443 |
Results | aneurysm occlusion | COMPLICATIONS | A total of 124 patients were enrolled in the study. Overall, 58 patients were assigned to the Numen group, and 66 were assigned to the Axium group. At the 6-month follow-up, the successful aneurysm occlusion rate was 93.1% (54/58) in the MicroPort NeuroTech group and 97.0% (64/66) in the Axium group, with a common odds ratio of 0.208 (95% confidence interval, 0.023–1.914; P = 0.184). Complications were comparable between the groups. | PMC10276443 |
Conclusions | INTRACRANIAL ANEURYSMS | Compared with the Aixum coil, the Numen coil is safe and effective in treating small intracranial aneurysms. | PMC10276443 |
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Trial registration | (13/12/2016, NCT02990156) | PMC10276443 |
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Keywords | PMC10276443 |
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Introduction | thrombosis, aneurysm, aneurysms, occlusion, ischemic stroke, unruptured aneurysms, disability | THROMBOSIS, RECURRENCE, ANEURYSM, ANEURYSMS, ISCHEMIC STROKE, INTRACRANIAL ANEURYSMS | Due to the unique structures of small aneurysms, technical difficulties exist in the treatment of small aneurysms, including ruptured and unruptured aneurysms. Compared with clipping, intravascular embolization has lower mortality and disability rates [In recent years, with the development of manufacturing technology, the performance of coil delivery has been optimized. At the same time, to reduce the recanalization rate and enhance the durability of endovascular treatment, various materials have been added, including hydrogels, polyglycolic acid, and nylon.[The Numen Coil Embolization System (MicroPort NeuroTech, Shanghai, China) is a new electric detachable bare-metal coil made of platinum-tungsten alloys. Preclinical studies have shown that it promotes thrombosis in the aneurysm sac and vascular endothelialization in the neck to treat intracranial aneurysms. Compared with other types of spring coils, there are various coils with small sizes and lengths, which ensure the safety of the endovascular treatment of small aneurysms.In addition to the invention of appropriate spring coils, auxiliary techniques, such as stent-assisted and balloon-assisted coiling, provide patients with a minimally invasive and effective option. Compared with coiling-only methods, stent-assisted coiling techniques show similar immediate occlusion rates, lower recurrence rates, long-term angiographic occlusion rates, and higher ischemic stroke and mortality rates [Many studies on the endovascular treatment of small aneurysms have been reported [ | PMC10276443 |
Materials and methods | PMC10276443 |
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Study design | aneurysm rupture, aneurysm, aneurysms | ANEURYSM, RECRUITMENT, ANEURYSMS, ANEURYSM RUPTURED, COMPLICATIONS, INTRACRANIAL ANEURYSMS | This study is a subgroup analysis of Catch data obtained from a prospective, multicenter, open-label, randomized controlled trial that includes patients treated with the Numen and Axium coil. The CATCH clinical trial includes patients treated with the Numen or Axium coil starting in August 2017 and concluding in December 2019, following the enrollment of 350 patients. The data of 140 patients whose aneurysms were smaller than 5 mm were extracted from the CATCH trial in this subgroup analysis. Details regarding the institutional review board and ethics committee approvals, patient population, and protocol requirements are described in the primary CATCH article.This subgroupanalysis was performed to assess the safety and efficacy of the Numen coil Embolization System in treating of small intracranial aneurysms (< 5 mm) compared with the Axium coil. Data for analysis were basic demographic information, including patient age, sex, and history of aneurysm rupture; aneurysm characteristics, including aneurysm size and location; procedural data, including packing density, devices used; and follow-up data, including any complications. Before commencing recruitment, the study was registered with the China Clinical Trial Registry (NCT02990156). | PMC10276443 |
Participants | aneurysm, intracranial lesion, unruptured intracranial aneurysm, cerebral arteriovenous malformation, stenosis | ANEURYSM, STENOSIS | At each clinical center, eligible patients were screened if they met any of the following criteria: The patient was aged 18 to 80; ruptured (World Federation of Neurologic Societies grade < IV) or unruptured intracranial aneurysm, as demonstrated by computed tomography angiography (CTA), magnetic resonance angiography (MRA) or digital subtraction angiography (DSA); complete aneurysm cure with one treatment; the diameter was < 5 mm; and written formed consent before enrollment. Ineligible patients were excluded according to the following criteria: any contraindications for endovascular treatment, angiography, or anesthesia; severe stenosis or occlusion in the parent vessel; and the presence of a cerebral arteriovenous malformation or an intracranial lesion. | PMC10276443 |
Randomization and masking | rupture | All eligible patient allocations were randomized at a 1:1 ratio based on an interactive Web response system. Information technology specialists developed the system from an independent clinical research organization. The online central randomization method ensured that the allocation was concealed. In addition, minimization criteria were applied to balance possible factors, including neck width, diameter length, location, and rupture status. Masking the treatment allocation to the investigators was not possible. However, members who followed up with trial subjects were blinded to the assignment. | PMC10276443 |
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Procedures | aneurysm, wide-necked aneurysms | SURGICAL COMPLICATIONS, ANEURYSM | All recruited participants performed routine preoperative examinations to reduce surgical complications. All procedures were performed under general anesthesia and via a transfemoral approach. After sheath placement, systematic heparinization was individually administered to maintain an activated clotting time of 250–350 s. Then, appropriate coils were implanted into the aneurysm sac through a microcatheter. It was suggested that the test or control group coil length used in each aneurysm should be more than 50% of the total length. For wide-necked aneurysms, remodeling balloons or stents were recommended as assist devices, excluding flow diverters and covered stents. The antiplatelet and anticoagulation regimens were left to the individual operator, according to the standard of each clinical center. The drug usage of each participant was recorded in detail from preoperatively to 12 months postoperatively. | PMC10276443 |
Clinical and radiological assessments | rupture, aneurysm occlusion, aneurysm | EVENTS, EVENTS, ANEURYSM, COMPLICATIONS | All participants underwent preoperative preparation, including clinical examination and angiographic assessment of the target aneurysm. Before randomization, the parameters collected included age, sex, and rupture status. In addition, other baseline data were obtained on aneurysm size and location. After surgery, the following data were collected on the coils, assist devices, complications, and angiographic images. At 1-month post-implantation, investigators followed up with each participant by telephone. DSA was recommended at the 6-month follow-up, while MRA was suggested at the 12-month follow-up. In addition, complications and additional interventions for the target aneurysm at any time were documented.Digital copies of imaging data before treatment, immediately after treatment, at the 6-month follow-up, and the clinical research organization collected during the 12-month follow-up. An independent core laboratory and Clinical Events Committee (CEC), comprised of three members qualified in neuroimaging or equivalent qualifications, located at the Sixth People’s Hospital, Shanghai, reviewed all the imaging and endpoint events. The degree of aneurysm occlusion was assessed according to the 3-class Raymond scale (complete occlusion, neck remnant, and residual aneurysm). The modified Rankin Scale (mRS) score was also obtained during the follow-up. | PMC10276443 |
Outcomes | aneurysm rupture, aneurysm occlusion, aneurysm | RECURRENCE, ANEURYSM, ADVERSE EVENTS, ISCHEMIC STROKE, SECONDARY, ANEURYSM RUPTURED | The trial’s primary outcome was the proportion of participants with successful aneurysm occlusion at the 6-month follow-up. Members of the independent core laboratory reviewed the digital copies of the imaging data and assessed the degree of aneurysm occlusion. Successful aneurysm occlusion was defined as Raymond class I or II. The secondary outcomes included the following: immediately successful aneurysm occlusion rate, complete aneurysm occlusion at the 6-month and 12-month follow-ups (complete aneurysm occlusion was defined as no contrast filling in either the sac or the neck of the aneurysm); recurrence rate at the 6-month and 12-month follow-ups; clinical deterioration rate at 6-month and 12-month follow-ups (clinical deterioration was defined as an mRS score > 2 and an increase of at least 1 point); and safety data at the 1-month, 6-month and 12-month follow-ups (including adverse events, such as ischemic stroke, intraoperative or delayed aneurysm rupture, and neurological sequelae).In addition, the total coil length and coil packing density were also recorded. The coil packing density was defined by dividing the coil volume by the aneurysm volume [ | PMC10276443 |
Statistical analysis | ADVERSE EVENTS, SECONDARY | The baseline characteristics of patients between groups were compared to verify intergroup differences. Medians with interquartile ranges were used for continuous variables, and proportions were used for categorical variables. The t-test or Mann-Whitney U test was used for continuous variables, and the χ2 test or Fisher exact test was used for categorical variables. The primary and secondary outcomes were studied using odds ratios with a 95% confidence interval, and the χ2 test or Fisher exact test was used for comparisons between groups. The number of adverse events was compared by using Fisher exact test. All analyses were performed using SPSS version 23 (IBM, Armonk, New York). All tests were two-sided, and P < 0.05 was considered statistically significant. | PMC10276443 |
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Results | PMC10276443 |
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Baseline results | ruptured aneurysm, aneurysm, aneurysms | RECRUITMENT, RUPTURED ANEURYSM, ANEURYSM, ANEURYSMS | Three hundred and fifty patients were recruited into the CATCH trial between April 2017 and October 2017 under randomization. Recruitment was stopped after the target number of patients had been recruited. The data of 140 patients whose aneurysms were smaller than 5 mm were extracted from the CATCH trial. The 140 patients formed the full analysis set (FAS) and underwent the treatments of interest. Due to the small size of the aneurysm sac in one ruptured aneurysm case, investigators failed to deliver coils into the sac. Among the 140 treated patients, 14 withdrew from the study without reason, non-conformance of one subjects with inclusion and exclusion criteria, and non-usage of coils in one subjects according to their random allocation. The remaining 124 patients formed the per-protocol set (PPS). The baseline characteristics of the patients and the aneurysms are shown in Table
Baseline characteristics of the per-protocol setData are No. (%), mean (SD), or median (interquartile range) | PMC10276443 |
Numen arm | aneurysm, aneurysms | RUPTURED ANEURYSMS, ANEURYSM, ANEURYSMS | Among patients allocated to the Numen group, the mean age was 56 ± 9.89. Twenty (34.48%) patients were male, while 38 (65.52%) were female. The mean aneurysm size was 3.85 ± 0.60 mm. Fifty-seven aneurysms (98.28%) were located in the anterior circulation, and 1 (1.72%) was found in the posterior circulation. Twelve patients (20.69%) were treated for ruptured aneurysms. Twenty-four patients (41.38%) were treated without using assistive devices. Stent-assisted coiling alone was used in 30 patients (51.72%), and balloon remodeling alone was used in 4 patients (6.90%). The mean packing density was 46.23 ± 23%, and the mean total coil length was 18.20 ± 10.97 mm. | PMC10276443 |
Axium arm | aneurysm, aneurysms | RUPTURED ANEURYSMS, ANEURYSM, ANEURYSMS | Among patients allocated to the Axium group, the mean age was 55 ± 9.57 years. Twenty-six (39.39%) patients were male, while 40 (60.61%) were female. The mean aneurysm size was 3.83 ± 0.82 mm. Sixty-five aneurysms (98.48%) were located in the anterior circulation, and 1 (1.52%) was in the posterior circulation. Nineteen patients (28.79%) were treated for ruptured aneurysms. Twenty-nine patients (43.94%) were treated without using assistive devices. Stent-assisted coiling alone was used in 36 patients (54.55%), and balloon remodeling alone was used in 1 patient (1.52%). The mean packing density was 45.50 ± 26%, and the mean total coil length was 21.29 ± 9.75 mm. | PMC10276443 |
Primary and secondary outcomes | thrombosis, allergic, fever, intraoperative ischemic stroke, stroke, vomiting,, ischemic stroke, headache | THROMBOSIS, ADVERSE EVENTS, STROKE, ISCHEMIC STROKE, SECONDARY, ARTERY OCCLUSION, EVENTS, COMPLICATIONS | Treatment and follow-up details are shown in Table
Primary and secondary outcomes evaluationData are No. (%). P < 0.05 was considered statistically significantStatistical analysis showed that complications were comparable between the groups. Overall, general adverse events occurred in 9/58 patients (15.5%) in the Numen group and 11/66 patients (16.7%) in the Axium group, with a common odds ratio of 0.680 (95% CI, 0.351–2.402, P = 0.862). Most of these events were symptoms, such as vomiting, headache, fever, or allergic response. In addition, there were 4 cases of intraoperative ischemic stroke (1 in the Numen group and 3 in the Axium group), which were considered after further examination by MRI and angiography. Among these 4 cases, the case of stroke in the Numen group and one in the Axium group were thought to be caused by parent artery occlusion; the other 2 cases were caused by intrastent thrombosis. All ischemic stroke patients recovered well after medical therapy and rehabilitation. | PMC10276443 |
Discussion | aneurysm, Intraoperative aneurysm rupture, aneurysms, Numen, small aneurysms, thrombus, saccular aneurysms, unruptured aneurysms, intracranial aneurysms | ANEURYSM, COMPLICATION, ANEURYSMS, THROMBUS, SACCULAR ANEURYSMS, EVENTS, COMPLICATIONS, INTRACRANIAL ANEURYSMS | Although several studies have been conducted to evaluate the safety and efficacy of the endovascular treatment of small intracranial aneurysms, randomized trials are still lacking. We extracted data from the CATCH trial and found that endovascular coiling techniques for treating small intracranial aneurysms are safe and feasible. Our results showed high success rates and complete occlusion immediately after endovascular surgery and during follow-up. According to a meta-analysis by Yamaki et al., technical success was achieved in 92% of patients, and 7% of aneurysms retreated [Intraoperative aneurysm rupture is a severe complication in the endovascular treatment of small aneurysms. The small size of the aneurysm sac limits the movement of the microcatheter [This study showed that the Numen coil was non-inferior to the Axium coil in treating small intracranial aneurysms. Unlike Axium coils, there are two types of three-dimensional (3D) coil shapes for Numen coils: 3/4 loops and 1/2 loops. The 3D coil with 3/4 loops is fabricated by a series of Ω-shaped loops, which provides a stable framing in the aneurysm sac. And the 3D coil with 1/2 loops is formed by a series of Ω-shaped and S-shaped loops incorporated for dense filling and safe finishing. The advantage of Numen coils includes: firstly, the anti-unwinding design improves its softness; secondly, the half size standard makes the selection more accurate; thirdly, the shorter caudal segment in length enhances the stability of the microcatheter. The coil packing density was suggested to be reduced, allowing slow thrombus formation in the sac [Although an additional assist device can facilitate coil packing, it may increase the incidence of complications, especially ischemic events [When dealing with small unruptured aneurysms, the natural history of these aneurysms should be considered [Only small saccular aneurysms were involved in this study, so the results only represent the treatment of one particular type of aneurysm. Well-controlled studies in the future were needed for validation. In addition, although we included aneurysms in the posterior circulation, there were only two cases of such aneurysms. Studies on using these techniques in treating aneurysms in the posterior circulation should be performed. | PMC10276443 |
Acknowledgements | We gratefully acknowledge Prof. Jielai Xia (Department of Medical Statistics, Fourth Military Medical University, Xi An, China) for providing guidance on the various statistical methods used in this study. We are grateful to all principal investigators and delegated physicians who enrolled the required participants in all the participating centers. We also thank the participants, their medical caretakers, and the families who consented to participate in the CATCH trial. | PMC10276443 |
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Author contributions | Conceptualization: Sheng Guan; Writing original draft preparation: Yazhou Jin; Methodology: Xinbin Guo; Formal analysis and investigation: Tao Quan; Resources: Rui Zhao, Tianxiao Li, Zhenwei Zhao, Hua Yang, Xingen Zhu, Guobiao Liang, Bing Leng, Xin Wu, Yang Wang; Supervision: Sheng Guan; Writing, review and editing: Sheng Guan; All authors reviewed the manuscript. | PMC10276443 |
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Funding | The trial was funded by the National Key R&D Program of China during the 13th Five-year Plan Period (Grant No. 2016YFC1300700), the National Key Clinical Specialty Construction Project, and the Project of the Shanghai Science and Technology Commission (Grant No. 17441907000) while being sponsored by unrestricted grants from the MicroPort Company. | PMC10276443 |
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Data availability | The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. | PMC10276443 |
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Declarations | PMC10276443 |
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Competing interests | The authors declare no competing interests. | PMC10276443 |
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Ethics approval and consent to participate | The study was approved by the ethics review board of Zhengzhou University First Affiliated Hospital (2017-09) in accordance with the Declaration of Helsinki. Written informed consent was obtained from all individual patients included in the study. | PMC10276443 |
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Consent for publication | Not applicable. | PMC10276443 |
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Abbreviations | EVENTS | Coil Application Trial in ChinaClinical Events CommitteeFull Analysis SetPer-Protocol Set | PMC10276443 |
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References | PMC10276443 |
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Objectives | SURGICAL COMPLICATIONS | To compare hearing outcome and surgical complications between endoscopic classic and reversal stapedotomies. | PMC10313534 |
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Patients and methods | otosclerosis | SURGICAL COMPLICATIONS, OTOSCLEROSIS | A prospective single blinded randomized clinical study carried out on 60 patients with otosclerosis who were randomized into two groups; each containing 30 patients. Patients in group 1 underwent endoscopic classic stapedotomy. Patients in group 2 underwent endoscopic reversal stapedotomy. Both groups were compared as regards hearing outcome and surgical complications. | PMC10313534 |
Results | SURGICAL COMPLICATIONS | The difference in the hearing outcome between the two groups was statistically non-significant. Post-operative closure of the air bone gap (ABG) within 10 dB was attained in 76.67% and 80% of patients in groups 1 and 2, respectively. The differences in the surgical complications between the two studied groups were statistically non-significant. | PMC10313534 |
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Conclusion | SURGICAL COMPLICATIONS | Endoscopic classic and reversal stapedotomies are comparable to each other as regards hearing outcome and surgical complications. The authors recommend further studies with relatively larger sample size. | PMC10313534 |
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