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Comparison of viral loads according to RDT result, and duration and intensity of symptoms
Viral loads (by NP PCR) were significantly higher in patients with RDT positive (median 1.9x10Log viral loads by NP PCR and saliva PCR according to A) RDT result and B) intensity band of positive RDT.The sensitivity of RDT according to symptoms duration varied between 80% and 90%. It was lowest the day of symptoms onse...
PMC9955963
Viral loads according to PCR type of sampling
VLs of patients with positive saliva PCR (median 1.3x10
PMC9955963
Comparison between log viral loads by nasopharyngeal PCR and saliva PCR.
VIRUS
A) Log viral loads in RDT positive (black dots) and negative (white dots) patients. Dotted lines: Mean log viral loads; Black line: Considered threshold for presence of cultivable virus (nasopharyngeal PCR); B) Bland-Altman analysis showing the difference between nasopharyngeal and saliva log viral loads; SD = Standard...
PMC9955963
Log viral loads by saliva PCR saliva volume: Low volume corresponds to a gingivo-buccal swab only; high volume corresponds to a gingivo-buccal swab with <0.5 ml of saliva in addition.
sore throat, anosmia, ageusia
SORE THROAT
The two PCR were equivalent also in patients with ageusia or sore throat and no other symptom outside anosmia (p = 0.7).
PMC9955963
Discussion
The results of the present study show that the detection rate of positive COVID-19 cases by RDT was high, especially for those with a VL of ≥10The detection rate of SARS-CoV-2 by PCR performed on a saliva sample was equivalent to that of RT-PCR performed on NP swabs. The sensitivity of PCR of one type of sampling compa...
PMC9955963
RDT versus PCR
cough, fever
The sensitivity of RDT of more than 95% in patients with VL≥10There was a slight variability in performance between the three different RDTs with STANDARD Q® having a higher sensitivity (93%) than those of PanbioIn our study, the specificity of all three tests was 100%, which is impressive considering the potential for...
PMC9955963
Saliva PCR versus NP PCR
Having a detection rate of saliva PCR equivalent to that of NP PCR is in line with a previous study done on 70 patients COVID-19 positive that showed excellent concordance between the two sampling methods [The median SARS-CoV-2 VL in saliva was approximately two log lower than that in the NP swab. With such a differenc...
PMC9955963
Clinical significance
If RDT would be used in settings with a lower SARS-CoV-2 prevalence, such as 10%, a negative test would have a negative predictive value (NPV) of 98.6%. Such an NPV is acceptable if the patients do not belong to high-risk populations (severe cases, hospitalized patients). If the prevalence would be only 1%, the NPV wou...
PMC9955963
Limitations
The present study was conducted in a well-defined outpatient population with usual testing criteria for COVID-19 and presenting within 7 days after symptom onset for most of them. Our results might not apply in a setting where patients would have lower viral loads and/or attend after one week of symptoms, keeping in mi...
PMC9955963
Conclusion
The good performance of the best available RDTs allows point of care management of patients at primary care level, as well as community testing aimed at stopping transmission chains. RDT results allow immediate isolation of the vast majority of contagious individuals, without confining unnecessarily those who are not. ...
PMC9955963
Supporting information
PMC9955963
Patient’s database.
(PDF)Click here for additional data file.
PMC9955963
Study’s protocol.
(PDF)Click here for additional data file.
PMC9955963
Strobe checklist.
(PDF)Click here for additional data file.
PMC9955963
TREND checklist.
René, Meige
MARION, MEIGE, RECRUITMENT
(PDF)Click here for additional data file.(XLSX)Click here for additional data file.We thank Yann Sancosme, Maxime Hostettler, Marion de Vallière and Maria Daniela Garrido for help in patient recruitment; Pierrette Meige, Catherine Mialet, Chantal Ngarambe, Tina Wyllie, Mani Souvannaraj, Annie Herard, Vincent Gliven, Ma...
PMC9955963
References
PMC9955963
Supplementary Information
SECONDARY, INSULIN RESISTANCE
In animal studies, β-nicotinamide mononucleotide (NMN) supplementation increases nicotinamide adenine dinucleotide (NAD) concentrations and improves healthspan and lifespan with great safety. However, it is unclear if these effects can be transferred to humans. This randomized, multicenter, double-blind, placebo-contro...
PMC9735188
Keywords
PMC9735188
Introduction
β-Nicotinamide mononucleotide (NMN) is a natural product which exists in small quantity in most plants, such as edamame, broccoli, and cucumber [Many preclinical studies on NMN supplementation have been reported [
PMC9735188
Materials and methods
PMC9735188
Study design, ethical approval, and participants
ICH, high-density lipoprotein, hemoglobin/erythrocytes, coronavirus disease 2019
BLOOD, SECONDARY, CORONAVIRUS DISEASE 2019, RECRUITMENT
This multicenter, randomized, parallel, double-blinded, placebo-controlled, dose-dependent clinical trial on NMN supplementation at daily oral doses of 300 mg, 600 mg, and 900 mg for 60 days aimed to test the effect of NMN supplementation on blood NAD concentration (primary outcome), safety, tolerability, and clinical ...
PMC9735188
Investigational product
The investigational product was food-grade NMN bulky powder with the brand name “AbinoNutra™NMN,” which was developed and manufactured by Aba Chemicals Co., Ltd. (Shanghai, China) in collaboration with Abinopharm, Inc. (Connecticut, USA) on manufacturing process development, quality control, and regulatory compliance. ...
PMC9735188
Procedures and outcome measurements
CRF
ADVERSE EVENTS, CRF
Participants were required to visit one of the two clinic centers four times. The first visit was for screening of eligibility; second visit (day 0) for baseline assessment and randomization; third visit (day 30) for mid-point efficacy, safety, and dosing compliance assessment; and fourth visit (day 60) for end-of-tria...
PMC9735188
Blood NAD concentration
Colorimetric NAD test kit from MyBioSource, Inc. (catalog# MBS841786; California, USA) was used for the measurement of NAD concentration in participants’ blood samples. The test measures the total blood concentration of NAD
PMC9735188
Safety and tolerability
ADVERSE EVENTS, ADVERSE EVENT
Safety evaluation of NMN supplementation was to assess if NMN would cause significant changes to clinical lab parameters from blood and urinary samples and to adverse events (AE) when compared to placebo and baseline. Clinical lab tests of blood and urinary samples were conducted at baseline and day 60. The lab clinica...
PMC9735188
Six-minute walking test
THORACIC
The 6-minute walking test was conducted by adapting the protocol issued by the American Thoracic Society [
PMC9735188
Blood biological age
The Aging.Ai 3.0 calculator (Insilico Medicine, Inc., Hong Kong and New York) [
PMC9735188
Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) test
The HOMA-IR was assessed by taking blood samples from participants when fasting at days 0 and 60. Fasting insulin and glucose levels was then measured by Suburban Diagnostics (Pune, India). HOMA-IR index was calculated by an online HOMA2 IR calculator at
PMC9735188
36-Item Short Form Survey (SF-36 Questionnaire)
Assess participants’ overall health status or quality of life [
PMC9735188
Statistical analysis
The statistical analysis was performed using the R software (version 4.1.2). Statistical significance was set at
PMC9735188
Results
PMC9735188
Blood NAD concentration
The NAD concentrations are given in Table Efficacy of the placebo and three NMN treated groups, comparisons of treatment over baseline within the same group Efficacy of the placebo and three NMN-treated groups, comparisons of the three treated groups vs. placebo, 600 mg vs. 300 mg, and 900 mg vs. 600 mg on the chan...
PMC9735188
Six-minute walking test
The walking distance of the six-minute walking test is given in Table Participants in the 600 mg NMN-treated group had a statistically longer walking distance compared to the 300 mg NMN-treated group at days 30 and 60 (both
PMC9735188
Blood biological age
Results of the blood biological age are given in Table
PMC9735188
HOMA-IR index
HOMA-IR results are summarized in Table
PMC9735188
SF-36 Questionnaire scores
SF-36 scores are summarized in Table
PMC9735188
Discussion
prediabetic, skeletal muscle
ADVERSE EVENTS, SECONDARY, OBESE, INSULIN SENSITIVITY
This randomized, double-blinded, placebo-controlled trial investigated the efficacy and safety of NMN supplementation with 300 mg, 600 mg, and 900 mg daily oral doses in healthy adults of 40-65 years old. The primary objective was to evaluate blood NAD concentration. The secondary objectives were to assess the safety a...
PMC9735188
Acknowledgements
RS
We would like to thank the teams of Suburban Diagnostics, Pune, India for testing all the clinic laboratory samples. We sincerely appreciate Professor Abel Zhou at University of Canberra for his insightful observations of our clinical data. Finally, we are thankful that Dr. Susan Cho from AceOne RS, Inc. in the USA hel...
PMC9735188
Author contribution
ABM
LY contributed to the trial design and wrote this report. ABM contributed to the data analysis and co-wrote this report. AV contributed to the trial operation overview and clinical study report (CSR). SP contributed to the clinical trial operations, data review, and analysis. ST contributed to the trial design, quality...
PMC9735188
Funding
The clinical trial is fully funded by Aba Chemicals Co. (Shanghai, China) and Abinopharm, Inc. (Connecticut, USA).
PMC9735188
Data availability
All data will be available on reasonable request to the corresponding author. A proposal will be needed for assessment of request.
PMC9735188
Declarations
PMC9735188
Conflict of interest
LY is an employee of Abinopharm, Inc., RT and ZL are employees of Aba Chemicals, Co., and AM, AV, SP, ST, NA, GA, and VK declare no conflict of interest.
PMC9735188
References
PMC9735188
Subject terms
COVID-19 (CORONAVIRUS DISEASE 2019), DISEASES
The purpose of this study was to determine the discount rates for money and health outcomes in the Thai context, including the discount rates for communicable and non-communicable diseases. Moreover, this study aimed to explore the socio-demographic characteristics that influence discounting. The computer-based experim...
PMC9969024
Introduction
DISEASES
Discounting is a method of adjusting the future costs and benefits of healthcare interventions such as devices, medicines, vaccines, procedures, and healthcare systems to their present value. The impact of discounting, according to the context of economic evaluation, is dependent on the timing of costs and benefits, im...
PMC9969024
Methods
A computer-based experimental design was used, along with a choice-based elicitation procedure, to obtain time preferences for money and health. The experiment based on money-related questions was carried out in all subjects. For health-related questions, the subjects were divided into two subgroups, one to answer ques...
PMC9969024
Experimental design
DISEASE, CORONAVIRUS DISEASE 2019
An experimental design method from a previous study by Attema et al.For each iteration, a choice-based elicitation procedure was performed to obtain the subjects’ time preferences. After subjects had chosen their preferred option, the next iteration was altered to make the chosen option less attractive and the non-chos...
PMC9969024
Population
cognitive impairment, a disability, acute illness
The sample size was calculated using a formula by Vaughan et al.The following subjects were eligible for this study: (1) Chiang Mai Province residents aged 25–50 years (as of September 30th, 2020) with Thai nationality according to the civil registration; (2) the participants must have lived in their own residence for ...
PMC9969024
Procedure
A total of 1202 subjects were asked to complete the money-related questionnaire. For health-related questions, all subjects were randomly assigned in a 1:1 ratio. A total of 602 subjects were assigned to the first group and were asked to complete a questionnaire about the COVID-19 situation. For the second group, 600 p...
PMC9969024
Study instrument
The questionnaires were developed based on the literature review and were revised in response to recommendations from the expert meeting. There were two versions of the questionnaire. The first version was associated with COVID-19 scenarios, whereas the second version was involved with air pollution caused by fine part...
PMC9969024
Outcomes
SECONDARY
The primary outcome of this study was the discount rates for money and health determined from the subjects' indifference values and the secondary outcome was the socio-demographic characteristics that influence discounting.
PMC9969024
Data collection
The officers in local organizations such as the District Office, District Public Health Office, Sub-district Municipality, and Health Promoting Hospital were contacted to coordinate and recruit the volunteers or subjects in the selected districts. The general Thai population that met the eligibility criteria of this st...
PMC9969024
Data analyses
The statistical analyses were divided into 4 steps. First, a choice-based elicitation procedure was performed to measure the individual’s indifference values of time preference for money and health outcomes. Second, the indifference values from each subject were summarized using descriptive statistics. Third, the cumul...
PMC9969024
Step 1: measurement of individual indifference values
A choice-based elicitation procedure was performed to obtain the subjects’ time preferences for money and health. The health and money profiles covered the next 20-year time interval. The time interval was divided into 7 time points: tThe elicitation procedure began at time point tNext, the elicitation of the remaining...
PMC9969024
Step 2: summary of the indifference values
The descriptive statistics were used to summarize the indifference values from the choice-based elicitation and were displayed as mean, standard deviation (SD), median, and interquartile range (IQR).
PMC9969024
Step 3: measurement of cumulative weights
The cumulative weighting functions were generated using the mean and median of the indifference values from each time point. The degree of discounting was indicated by the area under the cumulative weighting function. The greater the size of this area, the more the subjects discount the future.
PMC9969024
Step 4: measurement of discount factors and discount rates
The discount factors were computed from the cumulative weighting functions in the discounting modelCumulative weighting functions and discount factor equations.Remark: δ, κ, ∝ , r, and p represent parameters governing discounting model.To determine which discount model best described subjects' preferences, this study u...
PMC9969024
The effect of socio-demographic variables on discounting
Because the areas under the normalized weighting functions were censored between 0 and 1, the Tobit model was applied to investigate the relationships between discounting and socio-demographic characteristics
PMC9969024
Data analysis tools
Descriptive statistics and the Tobit model were performed using the STATA software version 14.0 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). The continuous approximation for discount rate was analyzed using R software (R Core Team. 2013. R: A language and environment for...
PMC9969024
Ethical approval and consent to participate
The ethics approval was obtained from the Institutional Review Board of the Faculty of Pharmacy, Chiang Mai University (Certificate of Approval No.006/2564/E). All procedures were carried out in accordance with the applicable guidelines and regulations. The study protocol was explained to all subjects. All subjects sig...
PMC9969024
Results
PMC9969024
Demographic characteristics
respiratory diseases
RESPIRATORY DISEASE, DISEASES
A total of 1202 subjects participated in the experiment, ranging from 25 to 50 years old, with a mean age of 37.3 ± 7.9 years. Of those, 66.6% were female, 40.9% were generation X (aged 42 years and above), and 42.4% were married. The average number of years of education was 12.9 (standard deviation; SD 0.1). The avera...
PMC9969024
Cumulative weighting functions
CORONAVIRUS DISEASE 2019
A table with descriptive statistics was presented in the Supplement (Table Cumulative weighting functions. COVID-19, Coronavirus disease 2019; PM2.5, Air pollution with fine particulate matter.The mean areas for the COVID-19 situation and the air pollution situation in the health scenario (Fig. Figure Relation between ...
PMC9969024
Discounting models
CORONAVIRUS DISEASE 2019
The analyses used 5 parametric forms to fit the cumulative weighting functions to determine which discount function best described subjects’ preferences. The medians of the individual estimates of the parameters in each of the models are shown in Table Estimated discount functions.Remarks: (1) Estimated discount functi...
PMC9969024
Effect of socio-demographic characteristics on discounting
respiratory diseases
RESPIRATORY DISEASE, CORONAVIRUS, REGRESSION, DISEASE, DISEASES
Table The effect of socio-demographic characteristics on discounting.COVID-19, Coronavirus Disease 2019.Remarks: (1) ( ) depicts the standard error.(2) Tobit model, with the left-censored value at 0 and the right-censored value at 1.(3) *,**,*** denote statistically significant at the 0.01, 0.05, and 0.1 levels, respec...
PMC9969024
Discussion
COVID-19 infection
RESPIRATORY DISEASE, COMMUNICABLE DISEASES, COVID-19 INFECTION, REGRESSION, DISEASES
To the best of our knowledge, this study is the experimental attempt to use a direct method to obtain time preferences for money and health in a large representative sample in Thailand. As the subjects discounted money more than health, discounting in this study was domain-specific. The correlation between discounting ...
PMC9969024
Conclusion
DISEASES
This study’s findings revealed that discounting for money was greater than discounting for health. Money and health had annual discount rates of 6.2% and 1.3%, respectively. Furthermore, in the COVID -19 situation, the annual discount rate for health was higher than that in the air pollution situation (2.4% vs. 0.7%). ...
PMC9969024
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-30559-2.
PMC9969024
Author contributions
P.B., U.P., and J.Y. initiated the study design and methodology. All authors participated in material preparation, subject enrollment, and data acquisition. J.Y. and P.B. performed the data analyses. J.Y. and U.P. drafted the manuscript. All authors contributed to the interpretation and validation of the results, revis...
PMC9969024
Funding
This study was supported by the National Research Council of Thailand (NRCT) under the Integrated Strategic Research Program on Social Sciences: Khonthai 4.0 (Grant No. 2563/5-04) and the Royal Golden Jubilee Ph.D. (RGJ-Ph.D.) Program (Grant No. PHD/0112/2561). The funders had no role in the design and conduct of the s...
PMC9969024
Data availability
All data generated or analyzed during this study are included in this published article and its supplementary information file. Additional raw data files can be available from the corresponding author upon reasonable request.
PMC9969024
Competing interests
The authors declare no competing interests.
PMC9969024
References
PMC9969024
Introduction
fractures, pelvic fractures, trauma
The incidence of low-energy pelvic ring fractures has sharply increased over the past decade and is projected to continue doing soDespite the increasing incidence of fragility fractures of the pelvis, adequate and evidence based treatment strategies are still missing. For high-energy trauma resulting in unstable and di...
PMC10522702
Materials and methods
trauma, fracture, fractures, fractureS
METASTATIC TUMORS, PATHOLOGIC FRACTURES, OSTEOPOROSIS
This randomized prospective nonblinded study (PRESS—Prospective Randomized Evaluation of Sacral fractureS), was conducted from October 2017 to April 2020 with a parallel design at the University Medical Center Hamburg-Eppendorf. The mid-term outcomes of two different treatment options in elderly patients with sacral fr...
PMC10522702
Treatment
dislocation, pain
SECONDARY
In the ST group, percutaneous minimally invasive navigated S1 sacroiliac screw osteosynthesis (Showing an X-ray postoperatively after percutaneous S1 Screw fixation and application of anterior supraacetabular external fixator.In the CCT group radiological follow-up imaging was performed after 3–5 days to exclude signif...
PMC10522702
Outcome measures
Data were collected at admission by Barthel questionnaires
PMC10522702
Statistical analysis
SPSS statistical program 25.0 (SPSS, Chicago, IL) and GraphPad Prism 9 (GraphPad Software, La Jolla, CA) were used for statistical analyses. Continuous variables are expressed as mean ± standard deviations (SD), while categorial variables are expressed as numbers and percentages. Normality distribution of the data was ...
PMC10522702
Sample size calculation
The sample size was calculated for the primary outcome, mortality at 24 months follow-up, with the scope of non-inferiority of the non-surgical. This calculation was performed considering the expected effect size, power, and design effect (log rank test). Based on a crossover rate of 11% reported by Höch et al.
PMC10522702
Ethical approval
This study conforms to the Declaration of Helsinki, was approved by the local research ethics committee called “Ärztekammer Hamburg” (reference number: PV5550) and was retrospectively registered with the German Clinical Trials Registry (DRKS00013703) on 10/12/2018.
PMC10522702
Consent to participate
mentally impaired, dementia
For this vulnerable group, written informed consent was obtained from all participants or their legal representatives. If no legal guardian was available but the patient was mentally impaired (dementia), a legal guardian was appointed by the Hamburg authority in an expedited procedure after a personal assessment by a l...
PMC10522702
Award
Trauma
This trial received the award as best evidence-based Study provided by the German Society for Orthopedic and Trauma Surgery (DGOU) in 2021.
PMC10522702
Complications and survival rate
infection
INFECTION, COMPLICATION
The median follow-up time was 12.9 months. Ten patients (25.6%) were lost to follow-up at 12 months. Three patients in the ST group and in the one patient in the CCT group died. Patients treated surgically showed a 17.6% complication rate (n = 3). One patient was diagnosed with a pin infection and loosening of the exte...
PMC10522702
Intention-to-treat and per protocol outcome analyses
When comparing the preoperative to the follow-up measurements in all patients in the ITT multivariate analysis, there was a significant decrease in VAS-pain (Short- and mid-term improvements of primary outcome measures.
PMC10522702
Discussion
death, pelvic fractures, pain, Tile B1, fractures, trauma
RECRUITMENT, APC, MEDICAL COMPLICATION
The aim of this study was to compare clinical outcomes as well as the one-year mortality of comprehensive conservative versus surgical treatment of low-energy posterior pelvic ring fractures that are typically found in older populations. We found no significant difference between the surgically and conservatively treat...
PMC10522702
Conclusion
fracture, fractures
The result of this randomized controlled pilot trial indicates that surgical treatment of FFP II fractures in geriatric patients may not be superior to conservative treatment. Non-displaced posterior pelvic ring fractures (FFP II) in an older population may be treated with comprehensive conservative therapy (analgesia ...
PMC10522702
Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-43249-w.
PMC10522702
Author contributions
D.M.T.: study conception and design, data collection, drafting manuscript, G.A.: data collection, drafting manuscript, A.S.: statistical analysis, T.R.: data interpretation, review manuscript, K.H.F.: review manuscript, L.K.: Data collection, statistical analysis, C.A.: data collection, drafting manuscript, T.B.: study...
PMC10522702
Funding
Open Access funding enabled and organized by Projekt DEAL.
PMC10522702
Data availability
The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.
PMC10522702
Competing interests
The authors declare no competing interests.
PMC10522702
References
PMC10522702
Background
The Delphi technique has steeply grown in popularity in health research as a structured approach to group communication process. Rating and ranking are two different procedures commonly used to quantify participants’ opinions in Delphi surveys. We explored the influence of using a rating or ranking approach on item pri...
PMC10436639
Methods
A randomized controlled parallel group trial was embedded in a three-round online Delphi survey. After an “open” first round, primary care patients, trained patient partners, and primary care clinicians from seven primary care practices were allocated 1:1 to a rating or ranking assessment group for the remainder of the...
PMC10436639
Results
Thirty-six panelists (13 clinic patients, 7 patient partners, 16 clinicians; 60% females) were randomized to the rating (
PMC10436639
Conclusions
A rating or ranking procedure led to modestly similar item prioritization in a Delphi survey, but ranking was more difficult. This study should be replicated with a larger number of participants and with variations in the ranking and rating procedures.
PMC10436639
Trial registration
Not applicable.
PMC10436639
Supplementary Information
The online version contains supplementary material available at 10.1186/s13063-023-07442-6.
PMC10436639
Keywords
PMC10436639