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Oral PFMT Instructions
pelvic floor muscle, constipation
VAGINA, RECRUITMENT, URETHRA
Both groups received oral PFMT instructions, comprising one-to-one health education about UI and PFMT practice guidance at the time of recruitment by experienced obstetricians, without further follow-up treatments. The health education content covered the following 5 topics: introduction to UI and lifestyle factors ass...
PMC10337423
Outcomes and Measures
PMC10337423
Baseline Measures
At baseline, participant demographic characteristics and pregnancy-related data, such as age, education, height, prepregnancy weight, number of pregnancies, and prior abortions, were collected through a self-designed electronic questionnaire (by scanning a QR code on the smartphone) before randomization. In addition, d...
PMC10337423
Primary Outcome
incontinence
INCONTINENCE, INCONTINENCE
The primary outcome was the severity of incontinence symptoms based on the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF) [
PMC10337423
Secondary Outcomes
Pelvic Muscle
URINARY INCONTINENCE, SECONDARY, INCONTINENCE
The secondary outcomes were quality of life, self-efficacy with PFMT, and knowledge of UI, measured at baseline, 2 months after randomization, and 6 weeks post partum.Quality of life was measured using the Incontinence Impact Questionnaire-7 (IIQ-7), with 7 items assessing 4 domains (physical activity, travel, social a...
PMC10337423
Protocol Changes
SUI, pelvic floor muscle strength
VAGINA, SECONDARY, RECRUITMENT
We have made several modifications to the original protocol before trial onset. First, the inclusion criteria were changed to gain additional insight into the preventive effect of the UIW app–based intervention. Therefore, we included all pregnant women regardless of UI status and type of UI, instead of recruiting only...
PMC10337423
Statistical Analysis
SECONDARY
Sample size estimation was performed using G*Power (version 3.1; Heinrich-Heine-Universität Düsseldorf) [An intention-to-treat approach was used in all data analyses that included all participants. Baseline data are shown as means and SDs for continuous variables and as counts and percentages for categorical variables,...
PMC10337423
Results
PMC10337423
Subgroups Analyses
URINARY INCONTINENCE, URINARY INCONTINENCE, INCONTINENCE
The post hoc subgroup analyses of the primary outcome revealed statistically significant interactions between subgroups of prepregnancy BMI, UI status during pregnancy, and baseline ICIQ-UI-SF scores, both at 2 months after randomization and 6 weeks post partum (Subgroup analyses of primary outcome at 2 months after ra...
PMC10337423
Adverse Events
ADVERSE EVENTS
There were no reported adverse events over the duration of the study.
PMC10337423
Discussion
PMC10337423
Principal Findings
To the best of our knowledge, this is the first trial that combines mHealth and PFMT to prevent and treat UI symptoms in Chinese pregnant women. The results of this study support the effectiveness of UIW app–based interventions in reducing UI symptom severity, UI impact on life, and enhancement of PFMT self-efficacy an...
PMC10337423
Limitations
incontinence
INCONTINENCE
This study has some limitations. First, there were no objective outcome measures. Although the primary outcome evaluation depended on self-reporting, which might have overestimated the improvement of incontinence, it may best represent incontinence from the patient’s perspective, and the self-reported instrument (ICIQ-...
PMC10337423
Implications for Future Practice
Given the high incidence of UI during pregnancy and post partum and its severe impact on quality of life, it is critical in clinical practice to provide effective PFMT guidance for pregnant women, which is a crucial component of the primary prevention of UI. This study showed that oral PFMT instructions in conjunction ...
PMC10337423
Conclusions
URINARY INCONTINENCE, LATE PREGNANCY
These results demonstrated that the UIW app–based mHealth intervention effectively reduced the severity of UI symptoms during late pregnancy, and the effect was sustained at 6 weeks post partum. In addition, participants receiving the app-based PFMT intervention also revealed higher levels of quality of life, self-effi...
PMC10337423
Abbreviations
floor muscle trainingstress
INCONTINENCE
Consolidated Standards of Reporting TrialsConsolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online TelehealthInternational Consultation on Incontinence Questionnaire-Urinary Incontinence Short FormIncontinence Impact Questionnaire-7mobile healthpelvic floor muscle trainingstres...
PMC10337423
Data Availability
The data sets used and analyzed during this study are available from the corresponding author upon reasonable request.
PMC10337423
Background
Inflammation
CHRONIC INFLAMMATION, HIV INFECTION, COMPLICATION, INFLAMMATION, ATHEROSCLEROSIS, DISEASES
Chronic inflammation has been described in people living with HIV (PLHIV) receiving antiretroviral therapy (ART) despite viral suppression. Inflammation associated non-communicable diseases, including atherosclerosis, are becoming recognized complication of HIV infection. We studied the effect of pitavastatin on athero...
PMC9969700
Methods
dyslipidemia
DYSLIPIDEMIA
A randomized, double-blind, crossover study was conducted in HIV-infected persons with dyslipidemia and receiving atazanavir/ritonavir (ATV/r) to evaluate the effect of 2 mg/day pitavastatin treatment versus placebo. High-sensitivity CRP (hs-CRP), cytokines, and cellular markers in PLHIV receiving 12 weeks of pitavasta...
PMC9969700
Results
A total of 24 HIV-infected individuals with a median (interquartile range) age of 46 (41–54) years were recruited, and the median CD4 T cell count was 662 (559-827) cells/mm
PMC9969700
Conclusions
Pitavastatin treatment increases basic FGF levels, and lowers HLA-DR
PMC9969700
Keywords
PMC9969700
Introduction
human immunodeficiency virus
HUMAN IMMUNODEFICIENCY VIRUS
The use of antiretroviral therapy (ART) in people living with human immunodeficiency virus (PLHIV) has evidently reduced opportunistic infection-related morbidity and mortality [Protease inhibitors are currently recommended as alternative agents for first-, second-, and third-line antiretroviral regimens [Statins posse...
PMC9969700
Materials and methods
PMC9969700
Study design and participants
dyslipidemia
DYSLIPIDEMIA
This study is a substudy of a randomized, double-blind, crossover study of 24 HIV-infected dyslipidemic patients receiving ritonavir boosted atazanavir (ATV/r) that was conducted to study safety and efficacy of pitavastatin for treatment of dyslipidemia (ClinicalTrials.gov NCT02442700) [Flowchart of subjects in the ran...
PMC9969700
Immunophenotyping
Peripheral blood mononuclear cells (PBMCs) from study donors were isolated by gradient centrifugation using Histopaque
PMC9969700
Cytokine and chemokine levels
Levels of cytokines and chemokines in plasma samples were measured in duplicate by multiplex bead array assays using a Bio-Plex Pro Human Cytokine 27-Plex Assay Kit (Bio-Rad, Hercules, CA, USA) according to the manufacturer's instructions. The concentrations of interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7,...
PMC9969700
Statistical analysis
Median, interquartile range (IQR), and frequency were used to describe patients’ characteristics. Changes of levels of cytokines and proportions of immune cell subsets from baseline were compared by Wilcoxon signed ranks test. A
PMC9969700
Results
PMC9969700
Cellular immune profiles
For the study of cellular biomarkers, pitavastatin treatment did not have a significant effect on changes in the proportion of T cells, CD4Baseline and changes in the proportions of immune cell subsets from baseline to week 12 after pitavastatin treatment vs. placebo baselineValues are shown as median (interquartile ra...
PMC9969700
Discussion
inflammation, dyslipidemia
INFLAMMATION, EVENTS, EVENTS, DYSLIPIDEMIA
We investigated the effects of pitavastatin on atherosclerotic-associated inflammatory biomarkers in PLHIV who had dyslipidemia and receiving ritonavir-boosted atazanavir. Although pitavastatin significantly lowered serum total cholesterol and LDL-cholesterol [The INTREPID study compared the effects of pitavastatin (4 ...
PMC9969700
Conclusions
We demonstrated that pitavastatin treatment, in addition to lipid lowering effect, could lower some of the atherosclerotic-associated cellular markers, including the proportions of HLA-DR
PMC9969700
Acknowledgements
We are grateful to all participants in this study.
PMC9969700
Author contributions
Conceptulization: SK, BT, AP. Data curation: AW, AP. Methodology: SK, BT, AP. Formal analysis: AP. Funding acquisition: AP. Investigations: AW, SK, AP. Project administration: SK. Writing—original draft: SSr, AP. Writing—review and editing: SSr, SSu, SK, BT, AP. All authors read and approved the final manuscript.
PMC9969700
Funding
This work was supported by Dr Prasert Prasarttong-Osoth Research Grant from the Medical Association of Thailand. The funding body had no role in the study design, data collection, analysis and interpretation and in writing the manuscript.
PMC9969700
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC9969700
Declarations
PMC9969700
Ethics approval and consent to participate
The study protocol was reviewed and approved by the Ethical Clearance Committee on Human Right Related to Research Involving Human Subjects of the Faculty of Medicine Ramathibodi Hospital, Mahidol University (MURA2014/18).
PMC9969700
Consent for publication
Not applicable.
PMC9969700
Competing interests
The authors declare no competing interests.
PMC9969700
References
PMC9969700
Background
inflammation, gingivitis, tooth
PERIODONTAL DISEASE, INFLAMMATION, GINGIVITIS, SECONDARY, SEVERE GINGIVITIS
Periodontal disease and lung function impairment were found to be associated with low-grade systemic or local inflammation, and it might be that gingival/periodontal inflammation triggers lung function due to systemic inflammation or the transfer of oral bacteria or its components to the lung. A recent observational st...
PMC9949689
Methods
biofilm-induced gingivitis, tooth
BLIND
The study has to include 120 non-smoking subjects aged between 18 and 30 years with biofilm-induced gingivitis. The chosen “waiting control group design” will compare the immediate intervention group with the delayed intervention group, which serves as a control group. Dental and gingival status, lung function and oral...
PMC9949689
Discussion
periodontitis, gingivitis
PERIODONTITIS, GINGIVITIS, INFLAMMATION
This proposed multidisciplinary study has several strengths. Only one previous intervention study with patients with severe periodontitis (mostly smokers) has been performed. It is novel to include non-smoking subjects with mild and potentially reversible oral inflammation. Furthermore, this research is innovative, bec...
PMC9949689
Trial registration
German Clinical Trial Register DRKS00028176. Registered on February 2022.
PMC9949689
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC9949689
Introduction
PMC9949689
Background and rationale {6a}
COPD, COPD exacerbations
COPD, PERIODONTAL DISEASES, LUNG, COPD EXACERBATION
Lung function has been established several decades ago as a major predictor of increased mortality later in life (as reported by [ Epidemiological findings on the associations between periodontal diseases and COPD and lower lung function in adults and potential biological mechanismsTherefore, the results of interventio...
PMC9949689
Objectives {7}
gingivitis
INFLAMMATION, SECONDARY, GINGIVITIS
The main objective is to test the hypothesis that gingivitis reduction via optimized daily oral hygiene and antibacterial chlorhexidine-containing (CHX) mouth rinsing improves lung function in terms of forced vital capacity (FVC), as an indicator of lung volume, by at least 2%. This allows interpreting the changes in l...
PMC9949689
Trial design {8}
gingivitis
GINGIVITIS
The design of this randomized clinical trial is a “waiting control group design”, which compares the immediate intervention group with the delayed intervention group. The latter one will serve as a control group. The intervention cannot be blinded, but the outcome measure (lung function tests) is blinded, because the t...
PMC9949689
Methods: participants, interventions and outcomes
PMC9949689
Study setting {9}
This study will be executed in the academic outpatient dental clinic at the Ludwig-Maximilians-University of Munich.
PMC9949689
Eligibility criteria {10}
diabetes, tooth
GUM BLEEDING, RECRUITMENT, CHRONIC DISEASES, DIABETES
The study subjects should have an age between 18 and 30 years, because of the life period with peak achievements of lung function.The following are the inclusion criteria:Non-smoking subjects with biofilm-induced gingivitisParticipants must be vaccinated against COVID-19Negative test result for COVID-19 before each den...
PMC9949689
Who will take informed consent? {26a}
The informed consent will be obtained by the recruiting dentists.
PMC9949689
Additional consent provisions for collection and use of participant data and biological specimens {26b}
On the consent form, participants will be asked if they agree to the use of their data should they choose to withdraw from the trial. Participants will also be asked for permission for the research team to share relevant data with people from the cooperating universities. This trial does not involve collecting biologic...
PMC9949689
Interventions
PMC9949689
Explanation for the choice of comparators {6b}
chronic kidney disease, diabetes
CHRONIC OBSTRUCTIVE PULMONARY DISEASE, DISEASES, CARDIOVASCULAR DISEASES, DIABETES
Safeguarding good and lifelong oral hygiene is a prerequisite for preserving dental and oral health. During the last decades, many associations between oral health—especially periodontal health—and general medical diseases, e.g. diabetes, cardiovascular diseases, adipositas/obesity, chronic kidney disease or chronic ob...
PMC9949689
Intervention description {11a}
PMC9949689
Intervention 1
caries
CARIES
The association between microbial dental biofilm and caries is known for decades [ Motivational interviewing, individualized demonstration and instruction for optimal, systematic and regular oral hygiene using a vertical brushing technique (e.g. BASS technique).Recommendation to use fluoridated toothpaste (fluoride con...
PMC9949689
Intervention 2
non-alcoholic, periopathogens improves gingival, inflammation, tooth, CHX mouth
INFLAMMATION
The professionally administered supra- and subgingival biofilm control goes hand-in-hand with the removal of periopathogens improves gingival inflammation [In addition to the professional tooth cleaning a full-mouth disinfection using a non-alcoholic, CHX-containing mouth rinse is included in the study protocol which h...
PMC9949689
Criteria for discontinuing or modifying allocated interventions {11b}
It is not planned to discontinue or modify the intervention for trial participants.
PMC9949689
Strategies to improve adherence to interventions {11c}
A key issue in maintaining the adherence of study participants is to explain the importance of the trial, to illustrate the study protocol and why it is important to adhere to the scheduled appointments and the given oral hygiene recommendation consistently. Furthermore, the acceptance of basic oral hygiene measures in...
PMC9949689
Relevant concomitant care permitted or prohibited during the trial {11d}
There are no restrictions regarding concomitant medical or dental care during study participation.
PMC9949689
Provisions for post-trial care {30}
The study protocol includes only established preventive dental interventions. Therefore, post-trial access to products or agents which are commercially non-available is not applicable for this trial.
PMC9949689
Outcomes {12}
The primary outcome is the pre- and post-bronchodilation lung function testing with the recording of the following clinical variables:Forced vital capacity (FVC)Forced expiratory volume in 1 s (FEVForced expiratory flow at 25–75% of the pulmonary volume (FEF
PMC9949689
Lung function testing by spirometry
Spirometry prior to bronchodilation will be performed in line with ATS/ERS recommendations [Specific attention will be paid to the requirement to obtain very precise and reliable lung function data. In addition to strictly following ATS/ERS recommendations, we will reach the goal of high-quality lung function testing b...
PMC9949689
Biosampling and measurements of the microbiome
STERILE, SECONDARY
The secondary outcome is considered the bacterial composition. Both saliva and gingival fluid will be collected from the participants. Gingival fluid between the teeth will be collected with sterile paper points at 6 per-protocol predetermined sites in the lower jaw (mesial and distal at the “Ramfjord” teeth 41, 44 and...
PMC9949689
Participant timeline {13}
The time schedule of enrolment, interventions (including any run-ins and washouts), assessments and visits for participants is illustrated in the following schematic diagram (Fig. Flowchart of the study
PMC9949689
Sample size {14}
periodontitis, gingivitis
PERIODONTITIS, PERIODONTAL DISEASES, GINGIVITIS
The calculation of the power of this study is complicated by the fact that only limited information on changes in lung function is available. The only published trial on oral sanitation and its impact on lung function included 2 × 30 subjects with severe periodontal diseases and an average age of 65.7 years. The author...
PMC9949689
Recruitment {15}
RECRUITMENT, GINGIVAL BLEEDING
The recruiting will start with the pre-selections of subjects with occasional gingival bleeding. These subjects are screened for further eligibility for the intervention study. The continuous recruitment will address primarily patients of dental school and university students.
PMC9949689
Assignment of interventions: allocation
PMC9949689
Sequence generation {16a}
The main aim of the randomized allocation process will be to
PMC9949689
Concealment mechanism {16b}
In principle, all participants will receive the same preventive measures owing to ethical reasons. Following the allocation of all subjects to one of the intervention groups, each participant will be informed by telephone about the appointment for the phase 2 baseline examination. As the protocol for the two groups—imm...
PMC9949689
Implementation {16c}
The generation of the allocation will be done by the data management group independently from clinicians.
PMC9949689
Assignment of interventions: blinding
PMC9949689
Who will be blinded {17a}
The clinical research group will be blinded against the data analysts. Trial participants cannot be blinded.
PMC9949689
Procedure for unblinding if needed {17b}
The design is open-label with only outcome assessors being blinded so unblinding will not occur.
PMC9949689
Data collection and management
PMC9949689
Plans for assessment and collection of outcomes {18a}
The clinical investigation plan is illustrated in Fig. 
PMC9949689
Plans to promote participant retention and complete follow-up {18b}
An important issue in maintaining the retention of study participants is to explain the importance of prevention for individual dental health and to illustrate potential effects on medical health which are investigated in the present trial. In addition, the acceptance of basic oral hygiene measures in all participants ...
PMC9949689
Data management {19}
Data management includes checks for the plausibility of all dental, spirometry data and microbiome data.
PMC9949689
Confidentiality {27}
Typically, the recording of all clinical data will be handled using paper-based case report forms. The data will be digitalized immediately to make a subsequent data analysis available. All data will be collected and stored on secured university-based computers to protect confidentiality before, during and after the tr...
PMC9949689
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Saliva and/or gingival samples collected during each of the follow-ups will be analysed with high-throughput sequencing techniques to characterize the bacteria that are present and to determine bacterial diversity. Bacterial DNA from the 16S rRNA gene will be isolated and the V3–V4 region of the 16S rRNA amplified and ...
PMC9949689
Statistical methods
PMC9949689
Statistical methods for primary and secondary outcomes {20a}
REGRESSION
Processing and evaluation of data include checks for the plausibility of spirometry data and microbiome data. Moreover, descriptive data analysis will be used to check the plausibility of the distribution of data. For evaluating contextual and compositional determinants, low and high levels of outcome data will be used...
PMC9949689
Interim analyses {21b}
The study protocol requires interim data analyses after the screening and wash-in phase. This analysis will be carried out by the data analysis group and has to be understood as a prerequisite for forming both intervention groups.
PMC9949689
Methods for additional analyses (e.g. subgroup analyses) {20b}
Descriptive and explorative analyses for the planned interventions are planned.
PMC9949689
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
In case of non-adherence, each individual will be contacted immediately and re-invited to follow the intended timeline. If individuals are unable to proceed with study participation, the corresponding data will be excluded from the phase 1 or phase 2 dataset (lost to follow-up).
PMC9949689
Plans to give access to the full protocol, participant-level data and statistical code {31c}
The datasets analysed during the current study and statistical code are available from the corresponding author upon reasonable request, as is the full protocol.
PMC9949689
Oversight and monitoring
PMC9949689
Composition of the coordinating centre and trial steering committee {5d}
The role of the trial steering committee is to provide overall supervision for the trial and provide advice to the trial management group at both study centres, data analysts and the sponsor. The administrators will review and implement the study protocol. Furthermore, they supervise the trial management group when it ...
PMC9949689
Composition of the data monitoring committee, its role and reporting structure {21a}
tooth polishing
ADVERSE EVENTS
This study uses approved widely used preventive agents, e.g. CHX, or products, e.g. tooth polishing paste, only. Therefore, the potential risk of adverse events is very low and justifies the decision that a data monitoring committee (DMC) is not needed.
PMC9949689
Adverse event reporting and harms {22}
ADVERSE EVENTS
This study uses only approved widely used preventive agents, e.g. CHX, and therefore, the risk of adverse events can be assessed as very low and justifies the decision that a systematic registration of adverse events is not included in the trial design.
PMC9949689
Frequency and plans for auditing trial conduct {23}
With respect to the non-availability of an external sponsor, it is not planned to engage an external trial auditor, and therefore, the study group is responsible by itself to ensure that all information is credible, i.e. that all scientific data has been generated, collected and processed are methodologically correct. ...
PMC9949689
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
The Ethics Committee of the Medical Faculty of the Ludwig-Maximilians University of Munich reviewed and approved the study concept (project number 019–998).
PMC9949689
Dissemination plans {31a}
Since the results of an interventional study are closer to derive recommendations compared to observational studies, a detailed dissemination plan of study findings will be developed. This plan goes beyond publication in high-ranked peer-review journals. It includes oral presentations at national and international cong...
PMC9949689
Discussion
decline of lung function, lung diseases
INFLAMMATION, LUNG DISEASES
This proposed study has several strengths: (1) It is novel, because it includes subjects with mild (and potentially reversible) oral inflammation. (2) It is innovative, because it includes oral sanitization with lung function testing and measurements of the oral microbiome. (3) It has a high public health relevance, be...
PMC9949689
Trial status
RECRUITMENT
At present, the study protocol is fully developed and an application for funding by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) is ongoing. It is planned to begin recruitment in 2022/23.
PMC9949689
Acknowledgements
There are no acknowledgements to provide yet.
PMC9949689
Authors’ contributions
All authors contributed equally to the project conception, the development of the study design and the writing of the manuscript. The authors read and approved the final manuscript.
PMC9949689