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Funding
Open Access funding enabled and organized by Projekt DEAL. The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
PMC9970129
Declarations
PMC9970129
Disclosure
PD, Sebastián A.
Dr. med. Esther Giehl-Brown, Dr. med. Sandra Dennler, Dr. med. Sebastián A. Garcia, Dr. med. Danilo Seppelt, Dr. med. Florian Oehme, Dr. med. Johannes Schweipert, MHBA, Prof. Dr. med. Jürgen Weitz, MSc and PD Dr. med. Carina Riediger, MSc, have no conflicts of interest or financial ties to disclose.
PMC9970129
References
PMC9970129
Background
febrile
Parents often contact out-of-hours services due to worry concerning febrile children, despite the children rarely being severely ill. As telephone triage of children is challenging, many children are referred to hospital assessment. This study investigated if video triage resulted in more children staying at home. Seco...
PMC10464404
Methods
death, febrile
In this prospective quality improvement study, nurse call-handlers enrolled febrile children aged 3 months-5 years to video or telephone triage (1:1), with follow-up within 48 h after call. The setting was an out-of-hours call-center for non-urgent illness in Copenhagen, Denmark, receiving over 1 million calls annually...
PMC10464404
Results
There was no difference in triage outcome (home care vs. hospital referral) or number of patients assessed at hospital between triage groups. However, more video triaged patients received in-hospital treatment, testing and hospitalization.
PMC10464404
Keywords
Open access funding provided by Royal Library, Copenhagen University Library
PMC10464404
Introduction
’ worry, febrile, fever
SECONDARY
Telephone triage is used extensively during out-of-hours (OOH) healthcare and is a crucial tool in prioritizing both pre-hospital and in-hospital resources. Telephone triage is a challenging task, and children, the relatively most frequent group of callers, are inherently difficult to triage. This is mainly due to seco...
PMC10464404
Methods
PMC10464404
Setting
injuries
EVENT, EMERGENCY
The study was conducted at the OOH Medical Helpline 1813 (MH1813) in Copenhagen, Denmark, which is open 24/7 for injuries and OOH for medical illness. An assessment at a hospital OOH in Denmark requires referral from either the Emergency Medical Services or an OOH service such as MH1813. Self-referral is largely discou...
PMC10464404
Design
fever, ill
A prospective quality improvement study design was used, where a group of experienced nurse call-handlers invited parents of young children to participate. In all calls matching the inclusion criteria and where the parent consented to participation, the call-handlers were instructed to perform standard telephone triage...
PMC10464404
Outcome measures
death
ADVERSE EVENTS, DISEASES, MINOR, ADVERSE EVENT
Outcome data were derived from four sources: MH1813 patient records, questionnaire responses from parents and call-handlers, and the hospitals’ patient charts. The primary outcome of the study was to investigate if video triage could result in 10-percentage points more patients being able to stay at home during the fir...
PMC10464404
Statistical analysis
REGRESSION
Patients’ baseline characteristics (age, gender, triage response and symptom) were described with frequency (number, percentage), median and interquartile range (IQR). Differences in triage response, symptoms registered by call-handler and hospital outcome between the video and telephone triage groups were analyzed usi...
PMC10464404
Ethics
EMERGENCY
The study was a quality improvement study, and the Research Ethics Committee in the Capital Region of Denmark deemed approval was not indicated (Journal number H-19037554), and participant consent was hence not needed. All participating parents were however informed about the study and gave verbal consent. The manageme...
PMC10464404
Results
PMC10464404
Discussion
fever, Non-Danish, ill, worry, tonsillitis
EAR INFECTIONS, MINOR, SECONDARY, TONSILLITIS
Our primary aim was to investigate if video triage could enable more ill children to stay at home, while also efficiently identifying potentially severely ill children with the need for assessment at hospital. There was not a difference in the number of patients triaged to stay at home or in the number of patients asse...
PMC10464404
Author contributions
ABH
The study was designed by CG, DC, GL, FF, MSF and ABH. CG conducted the experimental work and collected data. Analysis of data was done by CG, DC, AKE and HGJ. Interpretation of data was conducted by CG, DC, HGJ, GL, ABH, FF and HGJ. CG drafted the initial manuscript. Revising and commenting of manuscript was done by a...
PMC10464404
Funding
Open access funding provided by Royal Library, Copenhagen University Library. The study received unrestricted grants from the TRYG Foundation, the health research foundation of the Capitol Region and the Amager-Hvidovre Hospital research foundation. The funding bodies had no influence on study design or collection, ana...
PMC10464404
Availability of data and materials
The datasets used during the current study are available from the corresponding author on reasonable request.
PMC10464404
Declarations
PMC10464404
Consent for publication
Not applicable.
PMC10464404
Competing interests
The authors declare that they have no competing interests.
PMC10464404
References
PMC10464404
Abstract
PMC9932240
Objectives
MARF, bone dehiscence, postoperative pain
PERIOSTEUM
One of the simplest methods to increase keratinized gingiva is the modified apically repositioned flap (MARF) technique. In this method, the periosteum remains exposed, which may lead to postoperative pain and discomfort. In the presence of bone dehiscence, bone resorption and gingival recession may occur. Hence, this ...
PMC9932240
Material and Methods
MARF
In this randomized controlled trial study, 10 patients (six males and four females with a mean age of 33.9 ± 11.13) with less than 2 mm of attached gingiva bilaterally were treated by the MARF + PRF membrane (test group), on the one hand, whereas, on the other hand, it was treated only by MARF (control group). Clinical...
PMC9932240
Results
MARF
The attached gingival width increased significantly in both groups (1.7 mm in the MARF and 2.3 mm in the PRF) and this was greater in the PRF group (
PMC9932240
Conclusion
gingiva, MARF, reduced shrinkage, Postoperative pain
Using PRF with the MARF method significantly increased the width and thickness of the gingiva and reduced shrinkage compared to MARF only. Postoperative pain and vestibular depth changes were similar in both groups.
PMC9932240
INTRODUCTION
gingiva, Gingiva, bone dehiscence, postoperative pain
PERIOSTEUM
Gingiva is the part of oral mucosa that covers the alveolar processes of jaws and surrounds the neck of the teeth. The gingiva is divided anatomically into marginal (unattached), attached, and interdental areas (Newman et al., In this method, a horizontal incision is performed in the attached gingiva and a split‐thickn...
PMC9932240
MATERIALS AND METHODS
PMC9932240
Study design
MARF
This study was designed as a randomized controlled trial with a split‐mouth design. To participate in the study, the following inclusion and exclusion criteria need to be fulfilled. This study was done to evaluate the clinical results of using PRF in combination with MARF to increase the attached gingiva around the tee...
PMC9932240
Inclusion criteria
gingiva
Inclusion criteria in the study were: patients with less than 2 mm of attached gingiva at the buccal site; less than 5 mm of vestibular depth (VD); and the presence of high frenum pull bilaterally in the mandible.
PMC9932240
Exclusion criteria
SYSTEMIC DISEASE, PLAQUE
Exclusion criteria were systemic diseases, pregnancy and lactation, smoking, alcohol use, plaque index >20%, gingival recession Class 3 or 4 Miller, and PPD >5 mm.Patients were invited to participate in the study after being fully informed. Informed consent was obtained from all participants. The study was approved by ...
PMC9932240
Participants and randomization
MARF, Blindness
MAY, BLINDNESS
The present study was performed in the periodontics department of the Dentistry School of Hamadan University of Medical Sciences from May to September 2021; 10 people who had less than 2 mm of attached gingiva and needed soft tissue augmentation on both sides were selected.The sample size was determined based on the as...
PMC9932240
Surgical procedures
CAVITY
Chlorhexidine 0.2% was used for rinsing the oral cavity before surgery. Local anesthesia (lidocaine 2% with epinephrine 1:80,000) was performed in the buccal area of the premolars by mental nerve block.
PMC9932240
Control group (MARF)
PERIOSTEUM
A horizontal incision was made by a blade (no. 15) approximately 0.5 mm coronal to the mucogingival junction. The split‐thickness flap was elevated and the dissection was extended 5 mm in an apical direction. The coronal part of the flap would contain a band of keratinized tissue. The extension of the incision depends ...
PMC9932240
Test group (PRF)
MARF
STERILE, PERIOSTEUM
Patient's blood was collected into 10 ml sterile silica‐coated plastic tubes without anticoagulants (VACUETTE; Greiner Bio‐OneOne GmbH, Kremsmünster, Austria). At least two tubes were prepared, and the tubes were centrifuged immediately in a fixed‐angle centrifuge (Arman Teb Noor, Iran, Tabriz). According to studies by...
PMC9932240
Primary outcomes: Width and thickness of keratinized tissue
tooth
CAVITY, PERIOSTEUM
The patient's oral cavity was examined by a specialist with Williams Probe (Hu‐Friedy; Chicago, USA) to evaluate the clinical parameters. The evaluated parameters such as probing pocket depth (PPD), keratinized tissue width, VD, and gingival thickness (GT) were measured at the baseline, and after 8 weeks. GT measuremen...
PMC9932240
Secondary outcomes: Postoperative pain and wound shrinkage
postoperative pain, pain
SECONDARY
A secondary objective of the study was to assess postoperative pain. A visual analog score (VAS) questionnaire was used to evaluate the amount of pain, ranging from 0 (no pain) to 10 (worst pain), and the patients were asked to fill out the questionnaire on the VAS scales on the day after surgery.To assess the wound sh...
PMC9932240
Statistical analysis
The data were checked for normality in distribution using a normal quantile plot. The confidence level was determined at 95%. The patient was used as a statistical unit. After a rejection of normality, a paired
PMC9932240
RESULT
Postoperative pain, MARF, platelet‐rich, postoperative pain
PERIOSTEUM
Ten patients participated in this trial. The mean age was 33.9 ± 11.1 years old and the male/female ratio was 6:4. None of the subjects dropped out during the 8‐week follow‐up. One side of each patient was randomly assigned to the test (MARF + PRF) or control (MARF) group, while the contralateral side was assigned to t...
PMC9932240
DISCUSSION
postoperative pain, Postoperative pain, pain, MARF, bone dehiscence, Inflammation, LSCC
INFLAMMATION, ALMEIDA
A gingival width of 2 mm is sufficient to maintain healthy gingiva (Wennstrom & Lindhe, The apical repositioning flap introduced by Friedman increases the risk of bone resorption (Lang & Löe, In a 1‐ to 11‐year follow‐up study, Carnio et al. (The MARF and PRF groups resulted in a significant increase in keratinized tis...
PMC9932240
LIMITATION
Pain
This study was limited to the mandibular premolar area due to the split‐mouth design. Also, a small sample size may be subject to selection bias. Wound shrinkage will continue for months and the complete shrinkage assessed needs long‐term follow‐ups. Pain assessment one day after surgery may lead to bias.To substantiat...
PMC9932240
CONCLUSION
gingiva, MARF, reduced shrinkage, Postoperative pain
DEHISCENCE
Using PRF with the MARF method significantly increased the width and thickness of the gingiva and reduced shrinkage compared to MARF without PRF. Postoperative pain scores and VD changes were similar in the test and control groups. Increasing the GT may allow PRF to be used in the presence of bone dehiscence.
PMC9932240
AUTHOR CONTRIBUTIONS
PMC9932240
CONFLICT OF INTEREST
The authors declare no conflict of interest.
PMC9932240
ETHICS STATEMENT
The study protocol was registered on the IRCT registry, with Registration reference: IRCT20211124053173N1.
PMC9932240
ACKNOWLEDGMENTS
The authors would like to thank the dental research center and vice chancellor of research at the Hamadan University of Medical Sciences for their support. This research was fully funded by the research center, Hamadan University of Medical Sciences.
PMC9932240
DATA AVAILABILITY STATEMENT
The applicant has unlimited access to the data after sending the request via email to the corresponding author.
PMC9932240
REFERENCES
PMC9932240
Subject terms
beta-cell dysfunction, diabetes
SECONDARY, INSULIN RESISTANCE, TYPE 2 DIABETES, INSULIN SENSITIVITY, DIABETES
In early type 2 diabetes, the strategy of “induction” with short-term intensive insulin therapy followed by “maintenance” with metformin can stabilize pancreatic beta-cell function in some patients but not others. We thus sought to elucidate determinants of sustained stabilization of beta-cell function. In this seconda...
PMC10374648
Introduction
deterioration of pancreatic beta-cell function, T2DM
TYPE 2 DIABETES
The natural history of type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic beta-cell function over timeHere we show that one such strategy is the administration of initial short-term IIT (as induction therapy) followed by metformin (as maintenance therapy), an approach that has been s...
PMC10374648
Results
T2DM
The RESET-IT Main trial (ClinicalTrials.Gov NCT02192424) was a multi-centre, parallel arm trial in which adults with T2DM were randomly assigned to receive induction therapy with a 3-week course of IIT, followed by maintenance therapy consisting of either (i) metformin alone or (ii) metformin with intermittent 2-week c...
PMC10374648
Characteristics at Baseline and after 3-weeks Induction
Table Baseline characteristics of study population stratified into (i) participants who had sustained stabilization of beta-cell function for 2 years and (ii) those who did notContinuous variables presented as mean followed by standard deviation in parentheses (if normal distribution) or median followed by interquartil...
PMC10374648
Characteristics during maintenance phase
adiposity
ADIPOSITY
We next examined the maintenance phase (from 3-weeks to 2-years). Of note, the stabilization and non-stabilization groups did not differ in the maintenance therapy to which participants were randomized (Table Characteristics at completion of maintenance therapy at 2-years in (i) participants who had sustained stabiliza...
PMC10374648
Changes over time in metabolic variables.
(
PMC10374648
Determinants of sustained beta-cell stabilization
analysesTwo-sided
REGRESSION
Finally, we performed logistic regression analyses to identify independent determinants of the stabilization of beta-cell function at 2-years (Table Logistic regression analyses of (dependent variable) stabilization of beta-cell function over 2 years: (A) core model derivation and (B) sensitivity analysesTwo-sided We n...
PMC10374648
Discussion
weight gain, weight loss, T2DM, beta-cell dysfunction
REGRESSION, INSULIN RESISTANCE, INSULIN SENSITIVITY, GESTATIONAL DIABETES
In this study, we show that 55 of 99 patients with T2DM achieved sustained stabilization of beta-cell function over 2-years in response to induction IIT followed by metformin maintenance. These individuals had poorer beta-cell function than their peers at baseline but experienced greater recovery thereof in response to...
PMC10374648
Methods
This multi-centre clinical trial was approved by the research ethics boards of Mount Sinai Hospital (Toronto, ON), Western University (London, ON), and Hamilton Health Sciences (Hamilton, ON), which were sites where the study took place. The trial was registered at ClinicalTrials.Gov NCT02192424. It was conducted in ac...
PMC10374648
Study population
T2DM, liver disease
LIVER DISEASE
Inclusion criteria included age 30–80 years and duration of T2DM ≤ 5 years. Before the trial, participants could be treated with either metformin or lifestyle only. Exclusion criteria included treatment with anti-diabetic medication other than metformin, estimated glomerular filtration rate <50 ml/min, and known liver ...
PMC10374648
Randomization and Interventions
Participants stopped metformin (if applicable) and fasted overnight prior to the baseline visit, at which they completed a 2 h 75 g oral glucose tolerance test (OGTT). At this visit, they received instruction on healthy lifestyle practices for managing T2DMThese 2 treatment protocols have been described in detail previ...
PMC10374648
Physiologic Indices on OGTT
INSULIN SENSITIVITY/RESISTANCE
The serial 2 h 75 g OGTTs enabled assessment of physiologic indices reflecting insulin sensitivity/resistance and beta-cell function. Participants fasted overnight prior to each OGTT, with metformin held on the morning of the test. During each OGTT, venous blood samples were drawn at fasting and at 30-, 60-, 90- and 12...
PMC10374648
Outcomes
SECONDARY
The primary and secondary outcomes of the trial have been previously reported in detail
PMC10374648
Statistical Analyses
Statistical analyses were conducted with R 4.2.2, with two-tailed
PMC10374648
Reporting summary
Further information on research design is available in the 
PMC10374648
Supplementary information
Supplementary InformationPeer Review FileReporting Summary
PMC10374648
Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-40287-w.
PMC10374648
Acknowledgements
MOP 133701, Diabetes
GILBERT, DIABETES
RR holds the Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at Mount Sinai Hospital. SBH holds the Diabetes Canada Chair in Diabetes Management at Western University. SMR holds the Brian W. Gilbert Chair in Primary Health Care at Western University. HCG holds the McMaster-Sanofi Populat...
PMC10374648
Author contributions
R.R. and B.Z. designed the study. R.R., A.E., S.B.H., S.R., H.C.G., N.M., C.K.K. and B.Z. implemented the study and acquired the data. R.R. led overall study implementation. A.E. oversaw research coordination. J.P. performed the statistical analyses. R.R. wrote the manuscript. R.R. and J.P. verified the data. All autho...
PMC10374648
Peer review
PMC10374648
Data availability
De-identified data can be made available under restricted access from the corresponding author (Ravi.Retnakaran@SinaiHealth.ca), for academic purposes, subject to a material transfer agreement and approval of the Mount Sinai Hospital Research Ethics Board. Individual participant data that underlie the results reported ...
PMC10374648
Code availability
The code used for the statistical analyses is available at Github at the following link:
PMC10374648
Competing interests
N.M., Nordisk
R.R. reports grants from Boehringer Ingelheim, grants and personal fees from Novo Nordisk, personal fees from Sanofi, personal fees from Eli Lilly, outside the submitted work. SBH reports grants and personal fees from Sanofi, grants and personal fees from Novo Nordisk, grants and personal fees from AstraZeneca, persona...
PMC10374648
References
PMC10374648
Purpose
hematotoxicity
GLIOBLASTOMA
In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population.
PMC9886607
Methods
hematotoxicity, HAE
ADVERSE EVENTS, ADVERSE EVENT, REGRESSION
Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the ...
PMC9886607
Results
HAE
REGRESSION
HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was si...
PMC9886607
Conclusion
HAE
Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures.
PMC9886607
Trial registration
NCT01149109.
PMC9886607
Keywords
Open Access funding enabled and organized by Projekt DEAL.
PMC9886607
Introduction
HAE, Glioblastoma, hematologic adverse
GLIOBLASTOMA, PRIMARY BRAIN TUMOR
Glioblastoma is the most common malignant primary brain tumor in adults and has a detrimental prognosis despite standard-of-care treatment with surgery, radiotherapy, and temozolomide chemotherapy [The aim of the present study is to provide a detailed analysis of patterns, predictors and prognostic effect of high grade...
PMC9886607
Methods
PMC9886607
Study design, participants and treatment
HAE, neutropenia, leukopenia, anemia, lymphopenia
ADVERSE EVENT, NEUTROPENIA, THROMBOPENIA, LEUKOPENIA, ADVERSE EVENTS, ANEMIA, LYMPHOPENIA
The CeTeG/NOA-09 study design has been published previously [HAE were defined as thrombopenia, leukopenia, lymphopenia, neutropenia, or anemia of grade 3 or higher. All adverse events were rated according to the Common Terminology of Clinical Adverse Events (CTCAE) version 4.0 and documented using pre-specified clinica...
PMC9886607
Statistical analysis
HAE
REGRESSION
Standard descriptive statistics were used for all presented data. Group differences were analyzed with Fisher’s exact test for categorical variables, and Mann-Whitney U test for continuous and ordinal variables as normal distribution could not be assumed.Survival analysis was performed using Cox regression to analyze t...
PMC9886607
Results
PMC9886607
Patterns of hematologic adverse events grade 3 or higher
lymphopenia, HAE, hematotoxicity, neutropenia
ADVERSE EVENTS, NEUTROPENIA, LYMPHOPENIA
The prevalence of HAE was higher in patients treated with CCNU/TMZ compared to treatment with TMZ alone without reaching statistical significance (36.4% (24 of 66) vs. 28.6% (18 of 63), respectively, p = 0.36) as reported before [ Swimmer plot with individual patient data on applied chemotherapy courses and hematotoxi...
PMC9886607
Risk of recurring hematotoxicity
HAE
EVENTS
Among patients experiencing HAE, the median number of events was 1 (range, 1–4), with no difference between treatment arms (TMZ: 1 [range 1–4], CCNU/TMZ: 1 [range 1–4], p = 0.40). The risk of repeat HAEs during later courses among patients receiving at least one further course of chemotherapy after first HAE was 42.9% ...
PMC9886607
Impact of hematotoxicity on chemotherapy and survival
hematotoxicity, HAE
Chemotherapy was completed (i.e. concomitant + 6 adjuvant courses of TMZ or 6 courses of CCNU/TMZ) in 40.6% (26 of 66) of patients receiving CCNU/TMZ and 59.4% (38 of 63) of patients receiving TMZ, as reported before [According to protocol, chemotherapy was stopped if a course was delayed by more than 6 weeks. More pat...
PMC9886607
Discussion
HAE, hematologic adverse, toxicity, lymphopenia, glioma, hematotoxic, hematotoxicity
LYMPHOPENIA, EVENTS, GLIOMA
The present study provides a detailed comparative analysis of high grade hematotoxicity in the CeTeG/NOA-09 trial. No hematologic adverse event grade 5 was reported and the overall frequency of HAE showed a non-significant tendency to be higher with CCNU/TMZ as compared to TMZ [HAE patterns differed between the treatme...
PMC9886607
Author contribution
JW, CS and UH designed the analysis. JW performed data analysis and wrote the first draft of the manuscript. CS and UH supervised the work. All authors contributed to data acquisition, commented on previous versions and read and approved the final manuscript.
PMC9886607
Funding
Open Access funding enabled and organized by Projekt DEAL. The trial was funded by the German Ministry for Education and Science (Grant No. 01KG1005).
PMC9886607
Data availability
The dataset is available from the corresponding author upon reasonable request. The data are not publicly available due to privacy restrictions.
PMC9886607
Declarations
PMC9886607
Conflict of interest
Janssen-Cillag, Novocure
UH has received lecture and/or advisory board honoraria from Medac, Novartis, Daichii-Sankyo, Noxxon, AbbVie, Bayer, Janssen, and Karyopharm. CS has received lecture or advisory board honoraria from AbbVie, Bristol-Myers Squibb, HRA Pharma, Medac, Roche, and Seagen. GT has received lecture, consultant or advisory board...
PMC9886607
Informed to consent 
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Helsinki Declaration and its later amendments and the Guidelines for Good Clinical Practice. The study was approved by the Ethics committees of all participating centers.Written informed consent was obt...
PMC9886607
References
PMC9886607
1. Introduction
OA, inflammation, osteoarthritis, arthritis, pain, joints
RHEUMATOID ARTHRITIS, INFLAMMATION, JOINT DISEASES, OSTEOARTHRITIS, ARTHRITIS, DISEASES
Methylsulfonylmethane (MSM) is a food ingredient present in small amounts in many foods, and its anti-inflammatory effects have been reported. We conducted a randomized, double-blind, placebo-controlled trial of oral consumption of MSM on mild pain of the knee joint in healthy Japanese participants. A total of 88 parti...
PMC10346176
2. Materials and Methods
PMC10346176
2.1. Study Aim
knee pain
This study aimed to determine the effect of oral consumption of MSM on knee joint quality of life (QOL) in mild knee pain participants.
PMC10346176