title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Conclusions | The training intervention led to significant improvements in Clinical trial registered with | PMC10161761 | ||
Keywords | PMC10161761 | |||
At a Glance Commentary | PMC10161761 | |||
Scientific Knowledge on the Subject | PRETERM BIRTH | Preterm birth is associated with long-term cardiopulmonary risk. Young adults born preterm are reported to have a lower rate of | PMC10161761 | |
What This Study Adds to the Field | cardiovascular disease | PRETERM BIRTH, ELEVATED BLOOD PRESSURE, HYPERTENSION, CARDIOVASCULAR DISEASE | In this trial subgroup analysis of young adults with elevated blood pressure and stage 1 hypertension, a 16-week aerobic exercise training intervention led to significant improvements in peak exercise Preterm birth affects 10% of live births worldwide (Whole-body Cardiovascular fitness in early life has been shown to be important for long-term health. Shah and colleagues found that each 1-minute reduction in exercise test duration from baseline to year 7 of follow-up was associated with a 21% increased risk in all-cause mortality and a 20% increased risk of cardiovascular disease in long-term follow-up ( | PMC10161761 |
Methods | PMC10161761 | |||
Anthropometry | CREST | Height and weight were measured to the nearest centimeter and 0.1 kg, respectively, with participants’ footwear removed and light clothing worn. With a measuring tape, waist circumference was measured 2 cm above the iliac crest, and hip circumference was measured at the point of widest overall girth near the level of the greater trochanter of the femur or midbuttock. | PMC10161761 | |
Spirometry and Cardiopulmonary Exercise Test | CORTEX | All participants underwent spirometry testing according to standard guidelines by using the Cortex Metalyzer 3B (Cortex Biophysik GmbH) (Afterward, participants completed a peak cardiopulmonary exercise test on a seated stationary cycle ergometer (Ergoline GmbH) using a validated incremental protocol. Respiratory gases were measured breath by breath using the same Metalyzer as that used for spirometry. Continuous electrocardiogram monitoring was used to record heart rate, and blood pressure readings were taken every 4 minutes with a manual mercury sphygmomanometer (ACCOSON Freestyle). Participants maintained 60 revolutions per minute during the test, which started with one quiescent minute of resting measurements followed by 2 minutes of warm-up at 20 watts. After this, workload increased to 35 watts. To normalize test duration to 8–12 minutes, participants who reported higher activity or fitness levels had their workload increased to 75 watts after the warm-up. The workload was then increased in increments of 15 watts each minute, while participants cycled continuously until exhaustion prevented them from maintaining 50 revolutions per minute or safety termination criteria were met. The test ended with a 2-minute cool-down period at 50 watts and revolutions of the participant’s own preference. | PMC10161761 | |
Intervention | The intervention stipulated three 60-minute aerobic training sessions (completed on bicycle ergometers) on separate days per week for 16 weeks at an exercise intensity of 60–80% of peak heart rate measured at baseline. A wrist-worn heart rate and activity monitor (Fitbit Charge HR; Fitbit, Inc.) was gifted to the participants who were encouraged to wear it daily. To track physical activity in the intervention group, activity from the wrist-worn activity monitor was tracked using the Fitabase data management platform and records kept of training sessions attended. The compliance threshold for the intervention was set at 80%, equivalent to 39 or more independent training sessions, with no more than 2 weeks between sessions. A compliant session was defined, | PMC10161761 | ||
Statistical Analysis | stroke | STROKE | Baseline subgroup cohort characteristics were tested for normality by visual inspection of histograms and normal quantile-quantile plots. Continuous variables are presented as mean (standard deviation) when the data were normally distributed and median (interquartile range) when the data were non-normally distributed. Frequencies are presented as The main effects of the trial were analyzed by fitting general linear models with 16-week follow-up Subgroups (term- and preterm-born) were defined by splitting the gestational age variable from the minimization procedure (gestation: <32, 32–37, or ⩾37 weeks’ gestation) into two levels: ⩾37 and <37 weeks’ gestation. The subgroup analysis was then performed by fitting additional linear models, including an interaction term between treatment allocation (exercise, control) and gestational age category (⩾37 or <37 weeks’ gestation) to test whether the intervention effects would vary significantly across subgroups. Hence, for adjusted Complete case analyses were performed throughout. Model assumptions were tested and confirmed by plotting residuals versus fitted values. The results for preterm and term groups are presented as adjusted mean differences with 95% confidence intervals (CI). An α level of 0.05 was considered statistically significant. No adjustments were done for multiple testing. The cardiac index and stroke volume index (SVI) at the ventilatory anaerobic threshold and peak exercise intensity (CI | PMC10161761 |
Results | PMC10161761 | |||
Exercise Intervention: Preterm- and Term-born Subgroup Interaction Effects | term-born | Adding an interaction term to the model, as per Forest plot showing the main effects of a 16-week aerobic training intervention in the full-study group (black), followed by the subgroup effects for term-born (green) and preterm-born (blue) young adults on the primary outcome ( | PMC10161761 | |
Limitations | PRETERM BIRTH | Despite being prespecified, this study was an exploratory subgroup analysis and must therefore be regarded as hypothesis generating. As such, we were not able to explore all birth history factors related to preterm birth that may have impacted the response to the trial intervention. The cardiac index and SVI estimates were made on the basis of | PMC10161761 | |
References | PMC10161761 | |||
Background | IFI | INVASIVE FUNGAL INFECTION | Edited by: Gaoqian Feng, Nanjing Medical University, ChinaReviewed by: Jessica K. Roberts, Cognigen, United States; Paul Gubbins, University of Missouri–Kansas City, United StatesIn patients with invasive fungal infection (IFI), the steady-state serum trough concentration ( | PMC10410275 |
Aims | This randomized, prospective observational single-center study aimed to identify factors affecting VCZ- | PMC10410275 | ||
Results | Results indicated that CYP2C19 genetic polymorphisms might significantly impact VCZ loading and maintenance dose selection. CYP2C19 phenotype, C-reaction protein (CRP), and average daily dose/body weight were significant influencers on VCZ- | PMC10410275 | ||
Discussion | DiThis formula may serve as a valuable supplement to the Clinical Pharmacogenetics Implementation Consortium (CPIC | PMC10410275 | ||
Introduction | critically ill, ill, fungal infections, IFI | CRITICALLY ILL, FUNGAL INFECTIONS, INVASIVE FUNGAL INFECTION | Despite medical advances, fungal infections are a significant morbidity and mortality cause. Invasive fungal infection (IFI) in critically ill patients continues to present a hurdle and significant challenge for the clinician (However, individualized dose adjustment is critical to achieving optimal serum VCZ concentration. VCZ has non-linear pharmacokinetics due to its saturable metabolism. The proportion of exposure dose increase is much more significant than the dose increase for VCZ. Therefore, VCZ serum trough concentrations (VCZ-The high interindividual pharmacokinetic variability of VCZ is mainly influenced by the liver through cytochrome CYP2C19 and, to a lesser extent, by CYP2C9 and CYP3A4 (Therefore, the study aimed to (і) Determine the guiding significance of the CYP2C19 genetic polymorphisms for the initial loading dose of VCZ in ill patients; (ii) Determine factors affecting VCZ- | PMC10410275 |
Materials and methods | PMC10410275 | |||
Standard protocol approvals, registrations and patient consents | INVASIVE FUNGAL INFECTION | A prospective cohort study was conducted at Zhengzhou Central Hospital Affiliated to Zhengzhou University from August 2018 to August 2021. Hospitalized patients who met the following inclusion criteria were eligible for the study: (і) age ≥ 18 years old; (ii) diagnosed with invasive fungal infection according to the criteria established by De Pauw et al. (Study flow diagram. VCZ, voriconazole; | PMC10410275 | |
Treatment regimen and groups | The patients were randomly assigned to either the non-gene-directed group (Group A, | PMC10410275 | ||
CYP2C19 genotyping | CYP2C19 genotype was determined from peripheral blood, which was extracted and stored in an EDTA anticoagulant tube. Real-time fluorescence quantitative PCR (ThermoFisher Applied Biosystems 7500 fast PCR) was performed using a Human CYP2C19 gene detection kit (PCR-fluorescence probe method, Wuhan YZY Medical Science and Technology Co., Ltd, China) following the manufacturer’s instructions. Genomic DNA was isolated from whole blood using QIAamp DNA blood kits (Qiagen, Hilden, Germany). According to nomenclature by CPIC | PMC10410275 | ||
Serum VCZ trough concentrations assay | The blood samples collected from the enrolled patients were centrifuged at 3500 r/min for 10 minutes. VCZ- | PMC10410275 | ||
Cytokine concentrate assay | PCT | CRP, PCT, and IL-6 were detected using validated sandwich ELISA kits according to the manufacturer’s instructions at the Zhengzhou Clinical Laboratory Center. The interval for drawing blood between inflammatory factors and | PMC10410275 | |
Data collection | PCT | The hospital medical records of all patients included in the study were screened, reviewed, and analyzed by trained reviewers using a hospital information system. Clinical data were collected, including demographics, comorbidities, concomitant use of proton pump inhibitors (PPIs) and glucocorticoid, clinical information regarding VCZ dosing, duration of VCZ therapy, patients’ symptoms, body temperature, and chest X-Rays. Laboratory data included white blood cell counts, CRP, PCT, IL-6, gamma-glutamyl transpeptidase (GGT), AST, ALT, alkaline phosphatase (ALP), TBIL, albumin, blood urea nitrogen (BUN), serum creatinine (Scr), and Creatinine clearance. | PMC10410275 | |
Efficacy assessment of VCZ | death, IFI, toxicity, infection, Cancer | INFECTIOUS DISEASES, ALLERGY, INFECTIOUS PROCESS, INFILTRATES, INFECTION, MYCOSES, INVASIVE FUNGAL INFECTION, INVASIVE FUNGAL INFECTION, CANCER | Patients who received VCZ for suspected invasive fungal infection (IFI) were classified according to the Invasive Fungal Infection Group criteria of the European Organization for Research and Treatment of Cancer and Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Efficacy assessment was performed by a team of three physicians led by the chief physician. The final clinical response to VCZ was evaluated based on the patients’ clinical symptoms, laboratory data, the Galactomannan experiment, 1,3-β-D-glucan experiment, bacteriological findings, and computed tomography. The response was classified as complete, partial, or treatment failure, with a complete response being defined as the resolution of signs and symptoms of the infectious process, including chest X-ray, and a partial response is defined as at least a 50% improvement in pulmonary infiltrates and signs and symptoms of the infection. Treatment failure was defined as the withdrawal of the treatment due to poor response, toxicity, or death associated with the infection ( | PMC10410275 |
Safety assessment | hepatotoxicity, Hepatotoxicity | HEPATOTOXICITY | Hepatotoxicity was defined as ALT or AST more than three times the upper limit of the institution’s normal reference ranges (ALT 0–40 U/L, AST 0–35 U/L), or TBil more than two times the upper limit of the institution’s normal reference ranges (TBIL 5.1–22 umol/L). For patients with abnormal values at baseline, hepatotoxicity was defined as ALT or AST more than three times or TBil more than two times the baseline value. The relationship between hepatotoxicity and VCZ was evaluated. | PMC10410275 |
Statistical analysis | Statistical analyses and randomization were performed using the Statistical Package for the Social Sciences software (ver.19.0; SPSS Inc.). Data were presented as the number of categorical variables or as mean ± standard deviation (mean ± SD) or median values (minimum-maximum) and interquartile range (IQR) for continuous variables. Chi-squared or Fisher’s exact test compared groups for categorical variables. Comparisons were conducted using the Student’s t-test or the Mann-Whitney U-test for continuous variables, one-way ANOVA analysis of variance, or the Kruskal-Wallis test. Pearson’s correlation analysis was used to analyze the relationship between inflammatory markers and | PMC10410275 | ||
Results | PMC10410275 | |||
Baseline patient characteristics | The demographic and clinical characteristics of the included patients are presented in Demographic and clinical characteristics of subjects in different groups.Data are presented as the mean ± S.D. for continuous variables and as numbers for categorical variables. | PMC10410275 | ||
VCZ trough concentrations | A patient can undergo multiple
| PMC10410275 | ||
Correlations between Inflammatory factors and VCZ- | PCT | Twenty-eight out of 306 patients had complete indicators for VCZ-CRP, PCT, and IL-6 levels were significantly correlated with VCZ-
There were significant differences in CRP, PCT, and IL-6 levels among patients with VCZ- | PMC10410275 | |
This study, 306 patients were divided into groups based on PPIs (esomeprazole, omeprazole, pantoprazole, rabeprazole) and a control group. The demographic and clinical characteristics of the included patients are displayed in Demographic and clinical characteristics of subjects in all groups.Data are presented as the mean ± standard deviation or the medians (IQR) for continuous variables and the number for categorical variables.Values on day 1 of voriconazole therapy. The interval for drawing blood between inflammatory factors and VCZ-C
Each VCZ-
| PMC10410275 | |||
Clinical efficacy of VCZ and assessment of adverse drug reactions | hepatotoxicity | As shown in Comparisons of VCZ clinical efficacy among the groups.Data are presented as the number for categorical variables. A Chi-squared test, Compare the total favorable response (complete plus partial responses) in all groups.Out of 306 patients, 40 had hepatotoxicity. We assessed the effects of different levels of VCZ-The frequency of hepatotoxicity among groups. | PMC10410275 | |
Analysis of factors affecting VCZ- | Factors affecting VCZ-Correlation between VCZ-Data are presented as the number of categorical variables. A Chi-squared test compared categorical data. VCZ-C
VCZ-C | PMC10410275 | ||
Analysis of factors affecting VCZ maintenance dose | REGRESSION | A multiple linear stepwise regression analysis was performed using VCZ stable maintenance doses (Y) as a dependent variable and sex (x
VCZ, voriconazole; CRP, C-reactive protein; UM, Ultrarapid metabolizer; RM, rapid metabolizer; NM, normal metabolizer; IM, intermediate metabolizer; PM, poor metabolizer. | PMC10410275 | |
Establishment and validation of prediction model for VCZ stable maintenance dose | DISEASE | According to the admission order, the 302 patients were divided into the derivation and validation groups. There were no significant differences in the general clinical data (sex, age, body weight, albumin, co-administered PPIs, co-administered hormones, CYP2C19 phenotype, underlying disease, etc.) between the derivation and validation groups (In the derivation group, the stable maintenance dose was used as the independent variable (Y), and age (xThere was no significant difference between the predicted VCZ maintenance dose and the actual maintenance dose according to the predictive model and the actual maintenance dose (376.10 ± 57.87 vs. 374.00 ± 47.93 mg, The data of 13 patients with different rates (≥ 20%) were compared and analyzed. It was shown that the | PMC10410275 | |
Discussion | liver injury, inflammation, abnormal liver function, Liver dysfunction | REGRESSION, INFLAMMATION, DRUG INTERACTIONS, PCT | In many studies, most CYP2C19 mutations involved three common alleles in the Chinese Han population, namely CYP2C19 *2,*3, and *17 (Due to the high bioavailability of oral dosage form (96%) according to VCZ’s label, the intravenous and oral routes of administration are interchangeable when clinically indicated. In the study, 306 patients were treated with different routes of administration for VCZ (Intravenous, oral and sequential therapy). The results showed no noticeable difference in different routes of administration between groups A and B (Although CRP and IL-6 are known to be involved in the high fluctuation of VCZ-These findings indicate that high inflammation, reflected by CRP, PCT, and IL-6, can affect the pharmacokinetics of VCZ, resulting in an increase in Our study found that a multiple linear stepwise regression did not identify PPIs or glucocorticoids as significant covariates for VCZ exposure. These covariates may be due to multiple factors, such as high inflammation and poor metabolism genotype, that could mask the results of drug interactions. Previous studies have shown that VCZ exposure increases with the type of PPI used (Although CPICIn addition to the significant covariates that affect the VCZ maintenance dose mentioned above, several other covariates must be considered. Liver dysfunction affects the clearance of VCZ, and patients with abnormal liver function often experience increased VCZ exposure due to slowed clearance when using conventional doses. The established model is based on patients with normal liver function without considering the effect of liver injury on the dose. Therefore, for patients with abnormal liver function, the dose should be appropriately reduced based on the recommended dose of the model during clinical treatment with VCZ. For individual patients whose VCZ maintenance dose is less than 200 mg/d or more than 600 mg/d, a significant deviation from the predicted dose appears in the established prediction model. There may be some other influencing factors that still need to be discovered. | PMC10410275 |
Conclusions | Our study provides evidence of the variability of inflammatory factors affecting VCZ- | PMC10410275 | ||
Data availability statement | The original contributions presented in the study are included in the article/ | PMC10410275 | ||
Ethics statement | The studies involving human participants were reviewed and approved by The Investigational Review Board at Zhengzhou Central Hospital Affiliated to Zhengzhou University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. | PMC10410275 | ||
Author contributions | LZ, LC, and QX designed the research, analyzed and interpreted the data, performed the statistical analysis, drafted the manuscript, and incorporated feedback from all authors. ML and HL coordinated and managed study data acquisition. LZ, ZS, and HL examined all the specimens and collected clinical data. ZG, YG, HZ, and FQ collected clinical specimens, supervised data acquisition, and analyzed and interpreted data. WC co-conceptualized the study, designed the research, and revised the manuscript. All authors contributed to the article and approved the submitted version. | PMC10410275 | ||
Acknowledgments | The authors acknowledge the Translational Medicine Center, the Department of Respiratory Medicine, and the Department of Hematology at Zhengzhou Central Hospital for their assistance with TDM, blood samples, and clinical data collection. | PMC10410275 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10410275 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10410275 | ||
Supplementary material | The Supplementary Material for this article can be found online at:
Click here for additional data file. | PMC10410275 | ||
References | PMC10410275 | |||
Objective | thumb carpometacarpal osteoarthritis | The aim was to evaluate the cost-utility of a 3-month multimodal occupational therapy intervention in addition to usual care in patients with thumb carpometacarpal osteoarthritis (CMC1 OA). | PMC10314563 | |
Methods | A cost-utility analysis was performed alongside a multicentre randomised controlled trial including three rheumatology departments in Norway. A total of 180 patients referred to surgical consultation due to CMC1 OA were randomised to either multimodal occupational therapy including patient education, hand exercises, assistive devices and orthoses (n=90), or usual care receiving only information on OA (n=90). The outcome measure was quality-adjusted life-years (QALYs) derived from the generic questionnaire EQ-5D-5L over a 2-year period. Resource use and health-related quality of life of the patients were prospectively collected at baseline, 4, 18 and 24 months. Costs were estimated by taking a healthcare and societal perspective. The results were expressed as incremental cost-effectiveness ratios, and a probabilistic sensitivity analysis with 1000 replications following intention-to-treat principle was done to account for uncertainty in the analysis. | PMC10314563 | ||
Results | During the 2-year follow-up period, patients receiving multimodal occupational therapy gained 0.06 more QALYs than patients receiving usual care. The mean (SD) direct costs were €3227 (3546) in the intervention group and €4378 (5487) in the usual care group, mean difference €−1151 (95% CI −2564, 262). The intervention was the dominant treatment with a probability of 94.5% being cost-effective given the willingness-to-pay threshold of €27 500. | PMC10314563 | ||
Conclusions | The within-trial analysis demonstrated that the multimodal occupational therapy in addition to usual care was cost-effective at 2 years in patients with CMC1 OA. | PMC10314563 | ||
Trial registration number | PMC10314563 | |||
STRENGTHS AND LIMITATIONS OF THIS STUDY | A strength of the study is the involvement of a patient research partner throughout the conduct of the study, although it may be considered a limitation that only one partner was involved.Self-reported costs combined with several months between assessments may have biased the total costs of the study.We were unable to include medication costs, travel expenses or purchase of technical or medical equipment (except those provided as part of the study) in the analyses due to imprecise reporting. | PMC10314563 | ||
Introduction | Hand osteoarthritis, OA | HAND OSTEOARTHRITIS, JOINT DISEASE | Hand osteoarthritis (OA) is the most common joint disease,There is a common misconception that hand OA is a normal part of ageing, and that there is ‘nothing to be done’.Oppong The aim of this study was to perform a cost-utility analysis (CUA) of a 3-month multimodal occupational therapy intervention in addition to usual care versus usual care only in patients with CMC1 OA referred to surgical consultation. The outcome measure was quality-adjusted life-years (QALYs), and the costs were estimated both as direct and indirect costs and societal costs over a 2-year period taking a healthcare and societal perspective. | PMC10314563 |
Methods | PMC10314563 | |||
Study design and setting | RHEUMATISM | A CUA was performed alongside a multicentre randomised controlled trial (RCT) including rheumatology departments in three Norwegian hospitals (St. Olav’s Hospital in Trondheim, Haukeland University Hospital in Bergen and Haugesund Rheumatism Hospital) and is described in the protocol article. | PMC10314563 | |
Patient and public involvement | RECRUITMENT | A patient research partner from the Patient Research Panel at Diakonhjemmet Hospital, who had lived with hand OA for several years, was involved throughout the project. She participated in project meetings where she gave input to the project plan, recruitment procedure and information material as well as feedback on the interpretation and dissemination of the results. | PMC10314563 | |
Participants and randomisation | cognitive deficits | Patients referred by their general practitioner for surgical consultation due to CMC1 OA at the three rheumatology departments between 2013 and 2015 were considered eligible for the study if they could speak Norwegian and had no cognitive deficits. Eligible patients received information about the study, a written consent form and a questionnaire by post. Patients who agreed to participate were scheduled for an appointment with an occupational therapist (OT) at the hospital within 2 weeks after referral. After a baseline assessment, the patients were randomised to either a 3-month multimodal occupational therapy intervention or usual care. In Norway, the waiting period between referral and the actual surgical consultation was at the time this study was conducted between 4 and 6 months, and the intervention was conducted during this waiting period. Patients were assessed again immediately before surgical consultation (approximately 4 months after baseline assessment), and 18 and 24 months after the baseline assessment (
| PMC10314563 | |
Intervention | During the waiting period between referral and surgical consultation, the intervention group received a multimodal occupational therapy intervention in line with recommended first-line treatment.The control group received usual care, which generally means staying on the waiting list for consultation in specialist healthcare, that is, receiving no treatment in specialist healthcare. For the purpose of this study, the control group were assessed at the hospital at baseline and all follow-up time points by an OT. They received general written and oral information about hand OA. The control group had the same possibility as the intervention group to ask questions and be given advice.If necessary, patients in both groups could independently seek treatment in primary healthcare, such as a consultation with general practitioner or other healthcare personnel (this information was collected as part of this study). Both groups had a surgical consultation with a medical specialist approximately 4 months after the baseline assessment. All patients paid a deductible for the assessment consultations (a maximum of €259 per year). | PMC10314563 | ||
Randomisation and blinding | OA | Patients were randomised using a computer-generated list with a block size of 10, stratified by hospital. Envelopes were opened by the patients after receiving information on hand OA and completing baseline assessment. The group affiliation was known to both the patients and the OTs. | PMC10314563 | |
Data collection | PMC10314563 | |||
Health outcome | The health-related quality of life (HRQoL) was measured at baseline, 4, 18 and 24 months using the generic instrument EQ-5D-5L (EuroQol 5-dimension, | PMC10314563 | ||
Resource use and costs | disability | Healthcare usage was collected from different sources at baseline, 4, 18 and 24 months. The OT reported the number of consultations related to the intervention at each assessment, whereas surgical procedures and postoperative treatment were collected from patients’ medical record. In addition, the use of primary and specialist healthcare was self-reported by the patient. We have included the costs related to the OT assessment at baseline, 4 and 18 months for both groups (OT assessment at 24 months were not included as the usual care group then received the intervention). Although the OT assessment was done for study purposes, it was included in the cost estimates because we cannot rule out a possible positive effect of an appointment with an OT in specialist healthcare for the control group. We have not included medication costs, travelling expenses or purchase of technical or medical equipment (except assistive devices provided to patients in the intervention group) due to lack of or imprecise reporting. Many patients reported using medication when needed, making it impossible to calculate costs. Travelling expenses were not collected, and with regard to technical or medical equipment (except those provided as part of the project), it was not possible to determine if the patients had bought the equipment before or during the trial.Data on sickness absence related to surgery were collected from patient medical records. The number of hours of informal help at home due to OA (from spouse, family or friends) and the productivity loss (due to any reason of sickness absence and disability benefits, excluding sickness absence related to surgery) were self-reported. If not explicitly indicated by the patient, we expected that the productivity loss remained the same between assessment points, thus, if the patient reported sickness absence of 50% at 4 months and 100% at 18 months, this was calculated as 50% productivity loss between 4 and 18 months, and 100% between 18 and 24 months.The costs of specialist healthcare visits and surgery were calculated using diagnosis-related group (DRG) weights from 2019. DRG is a coding system used for administration of both clinical and financial activity in specialist healthcare. The DRG costs were estimated by multiplying the cost weighting for the specific DRG group of the patient with the unit cost of 2019.Direct costs included costs related to specialist healthcare (medical specialist, OT, physical therapist, nurse, radiographs surgery, assistive devices) and primary healthcare (general practitioner, physical therapist, manual therapist, acupuncturist, blood samples). Indirect costs included productivity loss due to sickness absence (due to surgery or for other reasons) and costs related to help with chores at home. | PMC10314563 | |
Statistics | Differences in QALYs between the two groups were estimated using the trapezoidal method (area under the curve).Cost-effectiveness (CE) plane of the incremental cost-effectiveness ratios of multimodal occupational therapy (intervention group) in addition to usual care (control group) were recalculated with 1000 replications of the study data using the bootstrap resampling method. The intervention is at the origin. QALYs, quality-adjusted life-years.Cost-effectiveness acceptability curve for direct costs, representing the probability that the multimodal intervention is cost-effective in addition to usual care. At a willingness-to-pay threshold of €27 500/QALY, the probability of multimodal intervention being cost-effective was 94.5%. QALYs, quality-adjusted life-years.Between-group differences in mean costs and mean effects were analysed using independent sample t-test. Significance level was set to 0.05. Statistical analyses were performed using Excel, SPSS V.26 and Stata V.16. | PMC10314563 | ||
Results | PMC10314563 | |||
Baseline characteristics | osteoarthritis, SD, Pain | OSTEOARTHRITIS | A total of 180 patients were randomised to either multimodal occupational therapy in addition to usual care (n=90) or usual care only (n=90). The mean age across both groups was 63 years (SD 7.6) and 79% of the patients were women. We found no between-group differences in any of the baseline characteristics including utility score, medication use or percentage of patients working full-time or part-time (Demographic variables for patients referred to surgical consultation due to thumb carpometacarpal osteoarthritis (n=180)All information was collected at the baseline assessment.Pain at rest was reported for referred hand (the mean of both hands if bilateral referral).*Comorbidities was categorised as present if they had any of 16 predefined comorbidities.CMC1, thumb carpometacarpal joint; NRS, Numeric Rating Scale. | PMC10314563 |
Missing data | SENSITIVITY | A total of 18 patients (7 in the intervention group and 11 in the control group) had missing HRQoL utility score at one or more timepoints. For these missing values we used ‘last observation carried forward’. Sensitivity analyses showed that the average HRQoL utility scores remained the same for both groups without imputation of these missing values. Missing self-reported costs were not imputed (n=16). The costs related to surgery were collected from patient medical records and were not encumbered by missing data. | PMC10314563 | |
Cost-utility analysis | absence or disability, SD, disability | The total between-group difference in QALYs was 0.06 (95% CI −0.02, 0.15) after 24 months, in favour of the intervention group. The distribution of EQ-5D-5L utility score across the different time points for the two groups are shown in
Mean direct and indirect healthcare costs (mean and SD) per patient for the intervention and control group (n=180)The table also shows unit price and the resource use (n).All costs are given in Euro (€1=Kr 10) and adjusted to 2019.*DRG (diagnosis-related group system).†List of reimbursement codes.‡Rates for physiotherapists.§Official statistics of average wage.¶Based on real costs.The mean cost of multimodal occupational therapy intervention (baseline information on hand OA, instruction in hand exercises, assistive devices, and customisation of orthoses, and adjustment of hand exercises and orthoses after 14 days) was approximately €500 per patient. Surgery accounted for the largest between-group difference related to direct healthcare costs with 22 surgical procedures in the intervention group and 33 surgical procedures in the control group, resulting in a €550 difference in surgical cost per patient between the two groups. The use of physiotherapy/occupational therapy also constituted a high cost. However, almost one-third of these costs were related to the predetermined assessment points (4, 18 and 24 months) that were part of the study but not the actual OT intervention (€375 per patient in the control group and €307 per patient in the intervention group).Productivity loss due to sickness absence or disability benefits was the largest contributor to the total costs in both groups. However, at baseline, only 7% of the sickness absence in both groups was reported to be due to hand OA, and the percentages at 4, 18 and 24 months were 6%, 2% and 0.5%, respectively. Similar numbers of patients in the two groups were retired at baseline (34% in the control group vs 32% in the intervention group), 4 months (36% vs 34%) and 24 months (42% vs 43%). However, more patients in the intervention group (43%) retired between 4 and 18 months than in the control group (36%), indicating that fewer patients contributed to productivity loss in the intervention group during this period.
Cost-utility analysis of mean costs (SD), mean effects (SD), incremental differences in costs and effects (95% CI) and incremental cost-effectiveness ratio (ICER) for direct and total direct and indirect costs (n=180)Direct costs, €: self-reported use of primary and specialist healthcare, including surgery.Indirect costs, €: productivity loss from sickness absence due to surgery, costs related to informal help at home, productivity loss from sickness absence and disability benefits excluding sickness absence due to surgery.Total cost, €: direct costs+indirect costs.*Mean effect without imputations; intervention group 1.58 (0.28), control group 1.51 (0.28). | PMC10314563 | |
Discussion | subluxation, OA, disability | DISEASE PROGRESSION | The aim of this study was to evaluate the cost-utility of a 3-month multimodal occupational therapy intervention in patients with CMC1 OA in a 2-year period. Our results demonstrate that the intervention, consisting of patient education, hand exercises, orthoses and assistive devices, has the highest probability of being cost-effective, given the willingness-to-pay threshold (€27 500/QALY). The results indicate that the intervention is both less costly and more effective when provided alongside usual care. This study is one of few studies to evaluate the cost-utility of conservative treatment in hand OA, and the only study to evaluate the cost-utility of the 2018 EULAR guidelines on first-line treatment for CMC1 OA. Our findings add to the evidence base by demonstrating that multimodal occupational therapy is a cost-effective alternative for the management of CMC1 OA.The results of this study are in line with a previous study showing that hand exercises were more cost-effective than leaflet and advice in patients with hand OA.In our study, we did not separately evaluate the different parts of the recommended first-line treatment. It is possible that we would have found the same results as Oppong Surgery constituted a large cost in this within-trial. Although we found a tendency towards reduction in surgical procedures in the intervention group compared with the control group, this result was not statistically significant.Productivity loss represented the largest contributor to the total costs in both groups. The between-group difference may to some extent be attributed to a higher retirement rate in the intervention group. Although most participants were of retirement age, we do not know the reason for retirement and this should therefore be reported in future studies. Additionally, to avoid bias, register data should be used for more accurate reporting of sickness absence and disability benefits.The patients reported to have OA complaints for a median of 5 years, and more than 60% showed radiographic signs of subluxation of the CMC1 joint, indicating advanced disease progression. However, only 21% of the patients had visited a physiotherapist or an OT before referral to surgical consultation.The current study is the first study assessing the cost-utility of recommended multimodal treatment in patients with CMC1 OA. It is considered a strength that the study was conducted alongside an RCT. The study also has some limitations. Almost 80% of the sample were women, which represents a higher proportion of women than the usual gender distribution in hand OA. The results may therefore not be representative for men with hand OA. The self-reported costs and the 14-month time frame between the reporting may have biased the total costs. This has most likely contributed to lower overall costs, as patients may not remember to report all consultations with healthcare personnel, especially in the time period between 4 and 18 months. On the other hand, the costs related to surgery were collected from patient medical records and will not be encumbered by the same bias. A total of 16 patients had missing data throughout the study. There may have been systematic reasons for these patients being missing, which could have affected the outcome. However, there were more missing data in the control group than the intervention group, indicating that the between-group difference could have been larger if all patients had reported direct and indirect costs. The results may have been biased by the method of imputation of missing HRQoL utility values. However, due to low number of missing values and sensitivity analyses showing no difference in mean score whether using ‘Last observation carried forward’ or not, we did not go any further with more advanced methods like multiple imputation. We were unable to include medication costs, travel expenses or purchase of technical or medical equipment, except for the assistive devices provided as part on the intervention, in the analyses. This is not in line with the most recent recommendations for cost-utility analyses | PMC10314563 |
Conclusion | The within-trial analysis demonstrated that multimodal occupational therapy was cost-effective in addition to usual care in patients with CMC1 OA, when taking a healthcare and societal perspective. The intervention was the dominant treatment with a 94.5% probability of being cost-effective at 2 years, given the willingness-to-pay threshold of €27 500/QALY. The low cost related to the intervention supports the use of this first-line treatment in all patients with CMC1 OA. | PMC10314563 | ||
Supplementary Material | PMC10314563 | |||
Reviewer comments | PMC10314563 | |||
Data availability statement | Data are available upon reasonable request. Data are available upon reasonable request to the project manager (Ingvild Kjeken, Ingvild. kjeken@diakonsyk.no). | PMC10314563 | ||
Ethics statements | PMC10314563 | |||
Patient consent for publication | Not applicable. | PMC10314563 | ||
Ethics approval | This study involves human participants and was approved by Norwegian Regional Ethical Committee (2012/2265/REK sør-øst C). Participants gave informed consent to participate in the study before taking part. | PMC10314563 | ||
References | PMC10314563 | |||
Abstract | premenstrual syndrome, inflammation, primary dysmenorrhea | PREMENSTRUAL SYNDROME (PMS), PMS, INFLAMMATION, DYSMENORRHEA, PRIMARY DYSMENORRHEA, PREMENSTRUAL SYNDROME | Premenstrual syndrome (PMS) and primary dysmenorrhea are common gynecological problems and inflammation may have a role in their etiology. Curcumin is a polyphenolic natural product for which there is increasing evidence of anti‐inflammatory and iron chelation effects. This study assessed the effects of curcumin on inflammatory biomarkers and iron profile in young women with PMS and dysmenorrhea. A sample of 76 patients was included in this triple‐blind, placebo‐controlled clinical trial. Participants were randomly allocated to curcumin (Curcumin supplementation significantly decreased serum levels of high‐sensitivity C‐reactive protein (hsCRP) in women with premenstrual syndrome and dysmenorrhea, but could not affect hematological inflammatory parameters including white blood cells (WBC) count, neutrophil percentage, mean platelet volume (MPV) and red blood cell distribution width (RDW). Curcumin was well‐tolerated, and none of markers of iron metabolism statistically changed after intervention.
| PMC10315327 |
BACKGROUND | inflammation, pain, tumor necrosis, dysmenorrhea | PREMENSTRUAL SYNDROME (PMS), TUMOR NECROSIS, PMS, ADVERSE EVENTS, INFLAMMATION, INEFFECTIVE ERYTHROPOIESIS, DYSMENORRHEA, COMPLICATIONS | Premenstrual syndrome (PMS) and dysmenorrhea are common menstrual associated complications which have a negative effect on well‐being and quality of life of women of child bearing age (Bahrami, Avan, et al., There are several parameters that can be used to assess hematological biomarkers derived from a complete blood count (CBC), including absolute counts of white blood cells (WBC), neutrophils as well as red blood cell distribution width (RDW), mean platelet volume (MPV), neutrophil: lymphocyte ratio (NLR), platelet: lymphocyte ratio (PLR), and RDW: platelet ratio (RPR) are novel inexpensive and reproducible indices indicating systemic inflammation in different conditions (Bilgin et al., RDW estimates erythrocytic heterogeneity in volume. Increased RDW reflects ineffective erythropoiesis and associated with higher cytokine levels such as interleukin (IL)‐1, IL‐6 and tumor necrosis factor‐α (TNF‐α) (He et al., HsCRP as an acute‐phase reactant released by the liver is strong index of inflammation. It has been shown that serum hsCRP levels vary during the menstrual cycle in PMS women together with physical and mood manifestations, which advocates the contribution of low‐grade inflammation in the etiology of PMS (Puder et al., Conventional treatment for PMS and dysmenorrhea may induce severe adverse events or be ineffective for relieving pain (Drevon, CUR has been reported to be safe with no serious adverse events even at doses as high as 8–12 g daily for 3 months (Karandish et al., Until now, some clinical trials have explored the effects of CUR administration on serum hsCRP value, but to the best of our knowledge have not assessed its effects on hematological parameters and iron metabolism. Taking into account wide‐ranging positive pharmacological and biological characteristics of CUR while we lack controlled trials among patients with both PMS and dysmenorrhea, the aim of this study was to assess the effects of CUR supplementation on iron profile, inflammatory hematological biomarkers and hs‐CRP levels among apparent healthy young women with PMS and dysmenorrhea. | PMC10315327 |
MATERIALS AND METHODS | PMC10315327 | |||
Study design and participants | gynecological disorders, bleeding, allergy, dysmenorrhea, PMS | BLEEDING, PMS, ALLERGY, DYSMENORRHEA, CHRONIC DISORDERS, PREMENSTRUAL SYNDROME, GYNECOLOGICAL DISORDERS | From December 2019 to March 2020, female students residing at five women’ university dormitories in Birjand (South Khorasan province, Iran), were invited for interview in the current randomized, triple‐blind, placebo‐controlled clinical trial. This study was supported by Birjand University of Medical Sciences, and registered at Iranian Registry of Clinical Trial (IRCT20191112045424N1; available at: Volunteers who fulfilled the following inclusion criteria were recruited into the study: (1) an age between 18 to 24 years; (2) a marital status of single; (3) menstrual cycle days between 21 to 35 days, with the bleeding time lasting 3–7 days; (4) not suffering from gynecological disorders and allergy to herbs or medicinal plants, and (5) definitely diagnosed with both moderate to severe dysmenorrhea and PMS by a gynecologist. Exclusion criteria included participants who: had either acute or chronic disorders based on history and medical examinations, taking any kinds of medications or supplements, and undergone stressful conditions throughout the trial.Menstrual patterns were evaluated using a questionnaire consisted of items concerning the age of menarche, menstruation cycle days and duration of bleeding. Gynecologist diagnosed women who suffered from dysmenorrhea and PMS by using visual analogue scale (VAS) and PSST (Premenstrual Syndrome Screening Tool), respectively (Ayadilord et al., Although 200 women were eligible to take part in this study, only 76 met the inclusion criteria and were chosen for this trial (Figure Flow chart of trial. | PMC10315327 |
Randomization, blinding and intervention | ® | BLIND | Eligible participants were randomly divided into either placebo or treatment (CUR) groups. While the CUR consisted of 500 mg curcuminoids +5 mg piperine (95%); C3 Complex (Sami Labs Ltd.), the placebo capsules contained inert filler (500 mg lactose powder) plus 5 mg piperine (Bioperine®, Sami Labs Ltd.). Bioperine® as bioactive alkaloid is purified extract obtained from With the intent of ensuring the triple‐blind design, CUR and placebo capsules were matched in shape, size and color, and the color of placebo (microcrystalline cellulose) was matched to that of CUR powder. The CUR and placebo powders (labeled as “code A" or “code B") were dispensed in identical blinded bottles. The Pharmacy Department of the Birjand University of Medical Science performed the randomization and blinding. The eligible volunteers were randomly assigned to one of the two arms “code A or B”. Next, a statistician provided a randomized list employing NCSS (statistical software) via the simple block randomization method based on CONSORT guidelines. The eligible study participants were assigned to one of the two groups “code A or B”, regarding to the randomized list. Participants with an even number on the registration list were enrolled to the CUR group; the remaining participants were put into the placebo group. Coding keys were sent to study's principle investigator through mail after the end of study and final analysis. Thus, neither the participants, nor the principal investigator and data analyst had been aware of the group allocation of the participants and had been blind to the capsule ingredients until the trial and data investigation were accomplished. With the aim of improving CUR's oral bioavailability and facilitating its absorption through intestines, piperine, a major bio‐active component of pepper was used in addition to CUR (Shoba et al., | PMC10315327 |
Blood collection | BLOOD | Twenty milliliter blood specimens were collected in the morning subsequent to a 12‐h overnight fasting. Blood samples were obtained from each participant 3 days prior to the intervention and within 3 days subsequent to the consuming last capsule. We used both serum separator tubes and EDTA tubes for the purpose of this study. Serum samples were stored −80°C in a reference laboratory until analysis. EDTA tube was used to quantify blood cell counts. | PMC10315327 | |
Complete blood count | BLOOD | Blood cell counts, hemoglobin levels, dimensional variables (MPV and RDW), and some combined parameters, such as NLR, PLR and RPR, were assessed by means of an automated commercial cell counter (Sysmex K‐800). All experiments were conducted in duplicate. | PMC10315327 | |
Measurement of | Serum hsCRP, Fe and total iron‐binding capacity (TIBC) levels were evaluated using commercial kits (Pars Azmun, Iran; catalogue numbers: 1027015, 1,022,001, 1,022,032 respectively) with auto‐analyzer (Prestige 24i, Tokyo Boeki Ltd.). Serum ferritin values were quantified using an enzyme‐linked immunosorbent assay (ELISA kit; Diazist, Tehran, Iran; RRID:AB_10575316) according to the manufacturer's instructions. Each test was performed in duplicate. | PMC10315327 | ||
Other variables | The anthropometric parameters and blood pressure of participants were measured using standard procedures in our health centers by expert paramedic staff as described previously (Askari et al., The dietary intake of study population was evaluated by a trained dietician by using a three‐day recall food records method (two weekdays and one weekend day) at the first and last week of the trial. Dietplan software (version 4, Forestfield software Ltd.) was used for estimation of daily mean of energy and macro‐ and micronutrients intake during the trial. | PMC10315327 | ||
Statistical analysis | Statistical data analyses were performed by using the Statistical Package for the Social Science software for Windows, version 18.0 (SPSS Inc.). All indices were presented as mean ± standard deviation (SD) or median and interquartile range (IQR). Non‐parametric tests were also used in the statistical analysis due to some parameters were not normally distributed (Kolmogorov–Smirnov test). The Student's | PMC10315327 | ||
RESULTS | PMC10315327 | |||
Recruitment | rash | A total of 76 subjects were recruited into the trial and 38 individuals were allocated to each of the groups. Of the total, 73 subjects completed the study: 36 in CUR group and 37 in placebo group. During the trial, 2 patients who reported rash side effects in the CUR group and one participant in the placebo group who unwilling to continue the study were lost to follow‐up (Figure | PMC10315327 | |
Comparison of baseline features between the two groups | Comparison of the baseline features of participants indicated no significant differences between CUR and placebo groups regarding to the mean age, blood pressure and anthropometric indices (Table Baseline features of study population.
Abbreviations: BMI, body mass index; DBP, diastolic blood pressure; SBP, systolic blood pressure; WC, Waist circumference.Using independent sample Dietary intakes of the study groups at baseline and after intervention.
Independent sample Paired sample | PMC10315327 | ||
Effect of the intervention on inflammatory biomarkers | After three menstrual cycle of intervention, significant decrement was observed in the median (IQR) serum levels of hsCRP in the CUR group [from 0.30 mg/L (0.0–1.10) to 0.20 mg/L (0.0–1.3); Comparison of hsCRP levels in curcumin and placebo groups before and after intervention.Comparison of inflammatory biomarkers in treatment groups before and after intervention.Bold values significant
Abbreviations: hsCRP, high‐sensitivity C‐reactive protein; MPV, mean platelet volume; NLR, neutrophil: lymphocyte ratio; PLR, platelet: lymphocyte ratio; RDW, red blood cell distribution width; RPR, red blood cell distribution width: platelet ratio; WBC, White blood cell.
| PMC10315327 | ||
Effect of the intervention on iron profile | The blood levels of Fe, ferritin, TIBC and hemoglobin showed no significant difference between the two groups at the baseline (Comparison of iron profile in treatment groups before and after intervention.
Abbreviations: Hb, hemoglobin; hsCRP, High‐sensitivity C‐reactive protein; TIBC, total iron‐binding capacity.
| PMC10315327 | ||
DISCUSSION | sepsis, critically ill, dysmenorrhea | CRITICALLY ILL, PMS, NONALCOHOLIC FATTY LIVER DISEASE, DYSMENORRHEA, SEPSIS, INFLAMMATORY RESPONSE | To the best of our knowledge, this study is the first clinical trial that has investigated the effects of CUR intervention on inflammatory markers and iron profile in women with both PMS and dysmenorrhea. Our study demonstrated that 3 successive menstrual cycle administration of oral CUR had considerable effect on hsCRP levels which decreased significantly in the CUR group by within‐groups analyses. CUR had no significant effect on measures of iron homeostasis in healthy women with PMS and dysmenorrhea.In our study, CUR oral supplements significantly reduced serum hsCRP levels. The results of two randomized clinical trial disclosed that nano‐formulate of CUR significantly mitigated mean serum hsCRP levels in patients with nonalcoholic fatty liver disease (Jazayeri‐Tehrani et al., The anti‐inflammatory effects of CUR might be associated with its phytochemical compounds. The potential positive effect of CUR on inflammatory response may be because of the modulatory effect of CUR on inflammatory signaling paths. It prohibits myeloid differentiation protein 2‐Toll‐like receptor 4 co‐receptor axes, induces peroxisome proliferator activated receptor‐γ (PPAR‐γ), suppresses the induction and phosphorylation of JAK/STAT proteins, and blocks mitogen activated protein kinase (MAPKs) cascade (Aggarwal et al., Since hs‐CRP has a non‐normal distribution, most studies present it as median (25th, 75th percentile) or apply log transformation or divide it into quartiles or quintiles for comparison (Rogowski et al., CUR had no significant effect on inflammatory hemogram parameters in this trial. Results of recent randomized clinical trial on critically ill patients with sepsis failed to demonstrate the nano‐curcumin had beneficial effect on NLR and PLR compared to placebo (Naeini et al., Our results indicate that three menstrual cycle CUR administration did not alter iron status in healthy women with PMS and dysmenorrhea. We evaluated iron status by measuring serum iron, ferritin and TIBC levels in our cases because decreased iron status was reported post long‐time curcuminoid feeding in previous in vivo studies (Chin et al., CUR acts as a free radical scavenger because of the enol form being a hydrogen donor or acceptor and has been reported to neutralize the detrimental effects of iron‐induced ROS generation (Ferrari et al., This was a sub‐study of our previous triple‐blinded controlled trial on CUR's effects on menstrual‐associated manifestations in young women with PMS and dysmenorrhea (Bahrami et al., | PMC10315327 |
CONCLUSION | IRON DEFICIENCY ANEMIA, DYSMENORRHEA, PMS | In conclusion, CUR was significantly more effective versus placebo in decreasing serum hsCRP, an inflammatory biomarker, in young women with PMS and dysmenorrhea. There are no significant differences between CUR intake and placebo regarding to the iron profile, while no treatment‐induce iron deficiency anemia were registered. However, further studies are warranted to get a definitive conclusion. | PMC10315327 | |
AUTHOR CONTRIBUTIONS | Afsane Bahrami conducted all analyses and drafted the manuscript. Amir Talebpour and Mahtab Mohammadifard coordinated the fieldwork of the study. Reza Zare Feyzabadi, Mahboube Tajik, Sara Mahmoudzadeh, Mansoore Saharkhiz and Hadis Rezapour provided methodological feedback. Afsane Bahrami and Gordon A. Ferns supervised the overall research project and helped to draft the manuscript. All of the authors have read and confirmed the final manuscript. All authors state that they have no conflicts of interest. | PMC10315327 | ||
FUNDING INFORMATION | This study was supported by grants [grant nu#456131(Afsane Bahrami)] from Birjand University of Medical Sciences, Birjand, Iran. | PMC10315327 | ||
CONFLICT OF INTEREST STATEMENT | The authors have no conflict of interest to disclose. | PMC10315327 | ||
CONSENT TO PUBLISH | Not applicable. | PMC10315327 | ||
ETHICS APPROVAL | Ethical approval was obtained from the Birjand University of Medical Sciences and informed written consent was completed by all participants (code: IR.BUMS.REC.1399.226). | PMC10315327 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.