title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
|---|---|---|---|---|
Findings | BPD, death | SECONDARY | In this secondary analysis of a randomized clinical trial including 799 extremely preterm infants, baseline risk for grades 2 to 3 BPD or death estimated using infants’ gestational age, birth weight, sex, respiratory support, and fraction of inspired oxygen was not associated with either benefit or harm from hydrocortisone exposure. | PMC10233424 |
Meaning | BPD, death, neurodevelopmental impairment | BRONCHOPULMONARY DYSPLASIA, SECONDARY | Differences in the association of hydrocortisone with death, BPD, or neurodevelopmental impairment were not identified when analyzed by infants’ baseline risk for BPD or death.This secondary analysis of a randomized clinical trial investigated whether estimated risk for grades 2 to 3 bronchopulmonary dysplasia or death is associated with the effect of hydrocortisone on the composite efficacy and safety outcomes among extremely premature infants. | PMC10233424 |
Importance | BPD, death, neurodevelopmental impairment, NDI | BRONCHOPULMONARY DYSPLASIA (BPD) | Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. | PMC10233424 |
Objective | BPD, death, NDI | To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. | PMC10233424 | |
Design, Setting, and Participants | SECONDARY | This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. | PMC10233424 | |
Intervention | Infants were randomized to 10 days of hydrocortisone or placebo treatment. | PMC10233424 | ||
Main Outcomes and Measures | BPD, death, NDI | Infants’ baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. | PMC10233424 | |
Results | BPD, death, NDI | Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. | PMC10233424 | |
Conclusions and Relevance | BPD, death | SECONDARY | In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. | PMC10233424 |
Trial Registration | ClinicalTrials.gov Identifier: | PMC10233424 | ||
Introduction | BPD, death, prematurity | BRONCHOPULMONARY DYSPLASIA (BPD) | Bronchopulmonary dysplasia (BPD) remains the most common serious morbidity of extreme prematurity,The recently conducted National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial compared hydrocortisone with placebo in extremely preterm infants receiving mechanical ventilation between postnatal days 14 and 28.The NICHD Neonatal BPD Outcome Estimator uses clinical covariates to estimate infants’ risk at various postnatal time points for the individual outcomes of death; mild, moderate, or severe BPD; or no BPD. | PMC10233424 |
Methods | BPD | SECONDARY | We performed a secondary post hoc analysis of the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial that enrolled 800 infants from 19 academic centers in the US. Participants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. The centers’ institutional review boards approved the trial, with written informed consent provided by a parent or guardian prior to enrollment. The trial protocol is found in The definition used for BPD was physiologic moderate or severe BPD assessed at a PMA of 36 weeks,Data were analyzed from September 13, 2021, to March 25, 2023. The primary outcome for the present analysis used the recently proposed evidence-based BPD grade definition To test model performance, in accordance with the Predictive Approaches to Treatment Effect Heterogeneity (PATH) statement recommendations,To describe the magnitude of effect modification, | PMC10233424 |
Results | A total of 800 infants were enrolled in the NICHD NRN Hydrocortisone Trial (421 boys [52.7%] and 379 girls [47.3%]) (eFigure 1 in Compared with infants within lower quartiles of baseline risk, infants in the higher quartiles had a lower median birth weight (800 [IQR, 690-925] g in quartile 1 vs 630 [IQR, 530-710] g in quartile 4) ( | PMC10233424 | ||
Demographic and Clinical Characteristics Used for Risk Estimates by Quartile of Baseline Risk for Grades 2 to 3 BPD or Death | BPD, death | BRONCHOPULMONARY DYSPLASIA | Abbreviations: BPD, bronchopulmonary dysplasia; FIn the primary analysis for heterogeneity of treatment effect in the efficacy outcome of grades 2 to 3 BPD or death, there was no significant interaction between baseline risk for grades 2 to 3 BPD or death and treatment on a relative or absolute scale ( | PMC10233424 |
Efficacy Outcome | BPD, death | BRONCHOPULMONARY DYSPLASIA (BPD) | The observed frequency (A), relative risk (B), and risk reduction (C) of grades 2 to 3 bronchopulmonary dysplasia (BPD) or death in the hydrocortisone vs placebo treatment groups are shown by quartile (Q) of baseline estimated risk of grades 2 to 3 BPD or death. Symbols (circles, squares, and triangles) represent estimated values by quartile of baseline risk; error bars indicate 95% CIs. The horizontal orange lines indicate the model estimated results; the horizontal blue lines and dashed lines indicate the overall trial result and 95% CIs, respectively. Grades 2 to 3 BPD or death did not differ by interaction between treatment group and baseline risk for grades 2 to 3 BPD or death. | PMC10233424 |
Outcomes by Quartile of Baseline Risk for Grades 2 to 3 BPD or Death | BPD, death, NDI | BRONCHOPULMONARY DYSPLASIA | Abbreviations: BPD, bronchopulmonary dysplasia; PMA, postmenstrual age.In the analysis of the safety outcome of moderate or severe NDI or death, there was no significant interaction between baseline risk for grades 2 to 3 BPD or death and treatment on a relative or absolute scale ( | PMC10233424 |
Safety Outcome | BPD, neurodevelopmental impairment, death, NDI | BRONCHOPULMONARY DYSPLASIA (BPD) | The observed frequency (A), relative risk (B), and risk reduction (C) of moderate or severe neurodevelopmental impairment (NDI) or death in the hydrocortisone vs placebo treatment groups by quartile (Q) of baseline estimated risk of grades 2 to 3 bronchopulmonary dysplasia (BPD) or death. Symbols (circles, squares, and triangles) represent estimated values by quartile of baseline risk; error bars indicate 95% CIs. The horizontal orange lines indicate the model estimated results; the horizontal blue lines and dashed lines indicate the overall trial result and 95% CIs, respectively. Moderate or severe NDI or death did not differ by interaction between treatment group and baseline risk for grades 2 to 3 BPD or death. | PMC10233424 |
Outcomes by Quartile of Baseline Risk for Moderate or Severe NDI or Death Between Birth and Follow-up | neurodevelopmental impairment | Abbreviation: NDI, neurodevelopmental impairment. | PMC10233424 | |
Discussion | BPD, death, NDI | LUNG DISEASE | In this analysis for heterogeneity of treatment effect in infants enrolled in the NICHD NRN Hydrocortisone Trial, baseline estimated risk for grades 2 to 3 BPD or death was not associated with the effect of hydrocortisone on observed grades 2 to 3 BPD or moderate or severe NDI or death. These findings are consistent with the primary analysis of the NICHD NRN Hydrocortisone Trial, which showed no effect of hydrocortisone on BPD or death or NDI or death.Our analysis was motivated by the multiple metaregression analyses of clinical trials of postnatal corticosteroids in preterm infants to prevent lung disease.While the overall results of a randomized clinical trial estimate the mean treatment effect for a therapy, an analysis for heterogeneity of treatment effect may identify a specific subpopulation for which there may be greater benefit or harm.Infants enrolled in the NICHD NRN Hydrocortisone Trial were at a particularly high risk for BPD or death. All required mechanical ventilation at 2 weeks’ postnatal age for inclusion in the trial. Therefore, the results of this analysis do not resolve whether there are potential differences in the effect of hydrocortisone in populations exposed at earlier postnatal ages or at different risks for BPD or death. In a randomized clinical trial of low-dose hydrocortisone (cumulative dose, 8.5 mg/kg) initiated within 24 hours after birth,There was no significant interaction for treatment effect by baseline risk for grades 2 to 3 BPD or death and the outcome of moderate or severe NDI or death in this analysis. Whereas previous evidence has supported a higher proportion of adverse childhood outcomes in infants with higher grades of BPD, | PMC10233424 |
Strengths and Limitations | BPD, death, NDI | Our analysis has several strengths, including being the first analysis, to our knowledge, of heterogeneity of treatment effect in a randomized clinical trial of corticosteroid exposure in extremely preterm infants. Moreover, this analysis assessed heterogeneity of treatment effect for both efficacy (BPD or death) and safety (NDI or death). In clinical practice, baseline risk of BPD or death is commonly used to weigh the benefits and harms of corticosteroid exposure in practice; however, to our knowledge, no individual patient-level data from a clinical trial have been analyzed to study this question. Moreover, as recommended by the PATH statement,A significant limitation of this investigation is that the available patient population had both a high and narrow distribution of baseline risk for grades 2 to 3 BPD or death, constraining our ability to analyze treatment effect heterogeneity compared with a population with a wider distribution of baseline risk. Finally, this post hoc analysis of the NRN Hydrocortisone Trial may not have been adequately powered to identify treatment effect heterogeneity; clinically relevant interactions between infant characteristics and treatment effect not identified in this analysis may exist. | PMC10233424 | |
Conclusions | BPD, death, NDI | SECONDARY | In this secondary analysis for heterogeneity of treatment effect in infants enrolled in the NICHD NRN Hydrocortisone Trial, baseline risk for grades 2 or 3 BPD or death did not modify the treatment effect of hydrocortisone for either observed grades 2 or 3 BPD or death or moderate or severe NDI or death. Similar analyses of other randomized clinical trials of corticosteroid exposure may be warranted to more precisely evaluate whether specific subpopulations of extremely preterm infants are more likely to benefit from or be harmed by systemic hydrocortisone treatment. | PMC10233424 |
Background and Objectives | headache disability, disability, pain | CHRONIC HEADACHES, HEADACHE DISORDERS | Go to This Null Hypothesis article is published as part of a collaborative effort between NeurologyThe Article Processing Charge was funded by the authors.Submitted and externally peer reviewed. The handling editor was Associate Editor Rebecca Burch, MD.Chronic headache disorders are a major cause of pain and disability. Education and supportive self-management approaches could reduce the burden of headache disability. We tested the effectiveness of a group educational and supportive self-management program for people living with chronic headaches. | PMC10065208 |
Methods | migraine, Headache, type headache, headache | MIGRAINE, MEDICATION OVERUSE HEADACHE | This was a pragmatic randomized controlled trial. Participants were aged 18 years or older with chronic migraine or chronic tension–type headache, with or without medication overuse headache. We primarily recruited from general practices. Participants were assigned to either a 2-day group education and self-management program, a one-to-one nurse interview, and telephone support or to usual care plus relaxation material. The primary outcome was headache related-quality of life using the Headache Impact Test (HIT)-6 at 12 months. The primary analysis used intention-to-treat principles for participants with migraine and both baseline and 12-month HIT-6 data. | PMC10065208 |
Results | migraine, headache | MIGRAINE, TENSION-TYPE HEADACHE, CHRONIC HEADACHE | Between April 2017 and March 2019, we randomized 736 participants. Because only 9 participants just had tension-type headache, our main analyses were on the 727 participants with migraine. Of them, 376 were allocated to the self-management intervention and 351 to usual care. Data from 586 (81%) participants were analyzed for primary outcome. There was no between-group difference in HIT-6 (adjusted mean difference = −0.3, 95% CI −1.23 to 0.67) or headache days (0.9, 95% CI −0.29 to 2.05) at 12 months. The Chronic Headache Education and Self-management Study intervention generated incremental adjusted costs of £268 (95% CI, £176–£377) (USD383 [95% CI USD252–USD539]) and incremental adjusted quality-adjusted life years (QALYs) of 0.031 (95% CI −0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained. | PMC10065208 |
Discussion | migraine, type headache, headache | MIGRAINE | These findings conclusively show a lack of benefit for quality of life or monthly headache days from a brief group education and supportive self-management program for people living with chronic migraine or chronic tension–type headache with episodic migraine. | PMC10065208 |
Trial Registration Information | Registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100 16th December 2015 | PMC10065208 | ||
Classification of Evidence | migraine, disability, headaches, pain | MIGRAINE | This study provides Class III evidence that a brief group education and self-management program does not increase the probability of improvement in headache-related quality of life in people with chronic migraine.Globally, headaches are second only to back pain as a cause of years lived with disability. | PMC10065208 |
Methods | PMC10065208 | |||
Study Design | CHRONIC HEADACHE | The Chronic Headache Education and Self-management Study (CHESS) was a randomized controlled trial conducted in 2 localities in the United Kingdom: Greater London and the Midlands. The protocol for this trial has been published. | PMC10065208 | |
Study Population | fits, headaches, ICHD-3, headache, migraine, type headache | TENSION-TYPE HEADACHES, SECONDARY, CHRONIC HEADACHES, MIGRAINE, CLUSTER HEADACHES | We primarily recruited from general practices, but people could self-refer. Participating general practices ran computer searches to identify people who had, in the previous 2 years, consulted with headaches or who had been given a prescription for a migraine-specific drug (triptans/pizotifen). After screening for those whom it would be inappropriate to approach, practices sent letters, with 1 reminder, inviting people to find out more about the trial. The study team contacted interested responders by phone to confirm eligibility and posted baseline questionnaires, paper or electronic headache diary instructions, and consent forms. When these were returned, we arranged a headache classification telephone interview with a research nurse. To exclude people with ineligible headache types requiring specific treatment, for example, cluster headaches, and to describe our study population, we used a previously validated headache classification interview.Our population of interest were adults meeting an epidemiologic definition of chronic headaches (≥15 headache days per month for at least 3 months) with migraine or tension-type headaches. For reporting, we identified 3 phenotypes, people with:
ICHD-3 criteria for chronic migraine; that is, at least 8 days per month with a migraine attack with or without aura,less than 8 migraine attacks per month, or any number of attacks meeting ICHD-3 criteria for episodic migraine and chronic tension–type headache, andchronic tension–type headache.The target population for this trial was people managed in primary care, many of whom do not have a formal headache diagnosis. Diagnostic advice was part of the intervention. This fits the point in the care pathway at which this intervention would be delivered. In this study, we report on these groups together reflecting the information needed by those who might want to commission this service in primary care. We excluded those unable to attend the group self-management sessions, without access to a telephone, not fluent in English, or unable to participate in the group intervention for health reasons.Our original objective was to test the effectiveness of an education and self-management support program for people meeting the epidemiologic definition of chronic headaches, with its effect on people with chronic migraine and those with chronic tension–type headache and episodic migraine as a secondary analysis. However, our feasibility study found that 95% of those recruited had either episodic or chronic migraine. | PMC10065208 |
Randomization and Masking | migraine, type headache, headache | MIGRAINE, MEDICATION OVERUSE HEADACHE | We used block minimization to randomize individual participants in batches of approximately 20 to ensure we could populate the self-management groups in a timely manner. We stratified by geographical locality (Midlands and Greater London) and 6 headache types (chronic migraine, chronic tension–type headache and episodic migraine, and chronic tension–type headache; each with or without medication overuse headache). The randomization program was written specifically for this trial by Warwick Clinical Trials Unit programming team. The algorithm minimized the imbalance between the 2 trial arms using the stratifying groups and ensuring the allocation ratio fidelity. Randomization was performed by a member of staff independent of the CHESS research team. We maintained strict allocation concealment and all baseline data were collected prior to randomization. It was not possible to mask the study team and participants from the treatment allocation. | PMC10065208 |
Intervention | pain | Our intervention development process has been published,Sessions were co-led by a nurse and another registered allied health professional (nurse, health psychologist, physiotherapist, chiropractor, or occupational therapist) and just once by a research assistant. All facilitators attended 2 consecutive days of training covering the educational and self-management components. The nurses delivering the one-to-one sessions attended an additional training day to cover the classification interview and medication advice.Study participants unable to attend the group they were originally allocated were offered 2 further groups to attend, if available. Quality control and assurance of the fidelity of intervention delivery was assessed by direct observation of sessions by members of the trial team with specific quality assurance feedback to facilitators as required. The protocol and results of the process evaluation have been published.Participants in the control group received a relaxation compact disk, something known to be a valued part of pain self-management programs. | PMC10065208 | |
Outcomes | Headache, pains, headache | Our primary outcome was headache-related quality of life measured using the Headache Impact Test (HIT)-6 at 12 monthsWe collected data on total headache days, average duration of headache, and headache severity from participants weekly for 6 months and then monthly, starting from the initial eligibility call to ensure we had prerandomization baseline data. Participants could report these outcomes either using a smartphone app or diary records.At baseline, we collected basic demographic data, including ethnicity (White, Black or Black British, Asian or Asian British, Mixed, and other ethnic group), self-identified gender (male, female, other, and prefer not to say), and data on the troublesomeness of any other bodily pains.To show a difference of 2.0 on the HIT-6 at 12 months with an SD of 6.87, 90% power, an intracluster correlation of 0.01, and an average cluster size of 10 in the intervention group required data on 523 participants (253 control, 270 self-management; allocation ratio, 1:1.07). | PMC10065208 | |
Statistical Analysis | Headache, anxiety, headache, migraine, depression, type headache | MIGRAINE, EVENTS, SECONDARY, ADVERSE EVENTS | Our analyses followed the prespecified statistical analysis plan available in the Supplement (For primary and secondary analyses, treatment effects were estimated using linear mixed-effects models with partial clustering to account for clustering in the self-management arm. Analyses were adjusted for age, gender, and the baseline value stratification factors. Adjusted treatment effect estimates and associated 95% CI are presented for all analyses. All statistical tests were 2-sided at the 5% significance level. As per analysis plan, if the proportion of people with chronic tension–type headache only was <15%, main analyses would be on the population with chronic migraine or chronic tension–type headache and episodic migraine.Drug use data for migraine (except Botox and calcitonin gene–related peptide monoclonal antibodies) reported in participant questionnaires were converted to amounts taken over the previous 28 days and then converted to defined daily doses (DDD).We predefined minimal adherence to the intervention as the participant attending day 1 of the intervention plus the one-to-one session with the nurse and full adherence as the participant attending the entire intervention. We performed complier averaged causal effect (CACE) analyses for both levels of adherence for the primary outcome only to estimate the difference between observed compliers (intervention) and potential compliers (control).We performed prespecified subgroup analyses to examine whether baseline anxiety (HADS anxiety subscale scores ≥11), depression (HADS depression subscale ≥11), and severity (HIT-6 ≤64 and >64) moderated treatment effect for primary outcome only.Headache days, headache duration, and severity were reported by participants at multiple time points. To account for the within-subject dependency, each outcome was analyzed using a mixed-effects model to estimate the treatment effect over time with random effects at the participant level. The models were adjusted for the same variables as in the primary analyses (fixed effects).We presented the primary outcome separately for the following: whole population, those with chronic migraine, or those with chronic tension–type headache and episodic migraine, and those with or without medication overuse. The small number with only chronic tension–type headache precluded presenting data on these individuals separately.We performed 2 sensitivity analyses: (1) excluding participants who were included in the process evaluation interviews andAdverse events (AEs) and serious adverse events (SAEs) were summarized as frequencies and percentages (%). If possible, the 2 arms were compared using either the χWe performed a prospective within-trial economic evaluation from the perspective of the UK National Health Service and Personal Social Services. | PMC10065208 |
Standard Protocol Approvals, Registrations, and Patient Consents | WEST | North West—Greater Manchester East Research Ethics Committee approved the trial (REC REF: 16/NW/0890). Participants provided written consent. The trial was registered on the International Standard Randomized Controlled Trial Number registry, ISRCTN79708100. The trial protocol is available in the Supplement ( | PMC10065208 | |
Data Availability | Individual participant data and a data dictionary will be available, subject to a data sharing agreement, for further prespecified analyses on request through Warwick Clinical Trials Unit ( | PMC10065208 | ||
Results | We approached 31,020 people from 166 general practices across London and the Midlands (combined list size = 1,529,684); 2,220 expressed an interest in the trial and 41 people self-referred. Of them, 1,912 (85%) were contactable, and 1,159 (61%) of them were eligible. We randomized 736 (64%) of these people between 24 April 2017 and 31 March 2019 ( | PMC10065208 | ||
CONSORT Chart | migraine, Migraine, type headache, headache | MIGRAINE, SECONDARY, MIGRAINE, MEDICATION OVERUSE HEADACHE | Because of the nature of the group intervention (fixed dates and times), not everyone who completed eligibility assessment could access the intervention; thus, it was not possible to randomize all those eligible for the trial (Nine participants (1%) had chronic tension–type headache, so our main analyses were on the remaining 727 with chronic migraine or chronic tension–type headache and episodic migraine. Of them, we classified 396/727 (54%) as having chronic migraine; 407/727 (56%) also had medication overuse headache (Baseline Characteristics of All Randomized Participants With Migraine by Treatment GroupDefined Daily Doses of Acute and Prophylactic Medications UsedWe held 42 self-management groups across 35 locations; 286/376 (76%) participants attended the first session, with a median group size of 6.5 (IQR 5–9), 259/376 (69%) achieved the predetermined minimum adherence (day 1 and one-to-one sessions), and 216/376 (58%) achieved full adherence to the program (eTable 15, We obtained analyzable primary outcome data from 586 participants with chronic migraine or chronic tension–type headache and episodic migraine (81%) at 12 months. There was no between-group difference in HIT-6 (adjusted mean difference, −0.3; 95% CI, −1.23 to 0.67; HIT-6–Adjusted Treatment Differences at Different Time PointsSmartphone app/diary data were poorly completed, median completion rate approximately 44%, making imputation inappropriate. The between-group difference over 12 months for the number of headache days was 0.2 (95% CI, −0.11 to 0.46; There were few differences in our secondary outcomes ( | PMC10065208 |
Treatment Differences and 95% CI for Secondary Outcomes, Adjusted for Age, Gender, Baseline Value of the Dependent Variable, Headache Type, and Geographical Locality at 4-, 8- and 12-Month Follow-ups | USD28,600, Anxiety | INTERACTIONS | Abbreviations: nC, number of participants from standard care; nSM, number of participants from self-management. Estimates and 95% CI rescaled to range from 0 to 100 for graphical representation purposes only. To obtain the estimated difference and its 95% CI in its original scale, the value from graph is multiplied by maximum value/100. For example, the estimated difference for HADS Anxiety at 4-month FU was −0.801 × 21/100 = −0.16821). See also eTables 17–19 (Treatment Effects and Treatment by Subgroup Interactions for Subgroup Analyses of the 12-Mo HIT-6 OutcomeThere were 7 AEs, 1 in the standard care arm and 6 in the self-management arm. There was 1 SAE; a participant in the standard care arm died of an unrelated cause (eTable 26, The CHESS intervention generated incremental adjusted costs of £268 (95% CI £176–£377) [USD383 (95%CI USD252–USD539)] and incremental adjusted QALYs of 0.031 (95% CI −0.005 to 0.063). The incremental cost-effectiveness ratio was £8,617 (USD12,322) per QALY gained. The incremental net monetary benefit was £354 (95% CI −£375 to £1,084) [USD506 (95% CI −USD536 to USD1,550)] with probability that the intervention is cost-effective, approaching 0.83 if the cost-effectiveness threshold is £20,000 (USD28,600) per QALY gained ( | PMC10065208 |
Cost-effectiveness Plane Displaying Incremental Costs and QALYs and Cost-effectiveness Acceptability Curves and Probability Estimate of the Intervention Compared With Usual Care at the Specified Willingness-to-Pay Thresholds | CHRONIC HEADACHE | (A) The graph shows the cost-effectiveness plane displaying 1,000 base-case ICERs simulated from the joint distribution of incremental costs and incremental QALYs. (B) Graph represents cost-effectiveness acceptability curves and gives a probability estimate of the CHESS intervention being cost-effective compared with usual care at the specified willingness-to-pay thresholds. Abbreviations: CHESS = Chronic Headache Education and Self-management Study; ICER = incremental cost-effectiveness ratio; QALY = quality-adjusted life year. | PMC10065208 | |
Discussion | chronic headache disorders, pain, headache-related disability, headache, migraine | MIGRAINE, CHRONIC PAIN, SECONDARY, HEADACHE DISORDERS | There was no indication that the CHESS intervention had any important beneficial effects on clinically relevant outcomes. Only at 4 months was there an indication, on balance, that there was beneficial effect on the HIT-6, −1.0 (95% CI −1.91 to −0.006); In our secondary outcomes, only for pain self-efficacy was there a benefit from treatment, observed at 4 and 12 months but not at 8 months. This may just be a chance finding because of multiple comparisons. However, it might indicate that our intervention does improve self-efficacy, one of our key intervention targets, but that this does not translate into a measured patient benefit.During trial design, the most appropriate measure for a population that may not have been given a headache diagnosis was the HIT-6.A quarter of people in the intervention group did not attend any treatment sessions. This was despite participants confirming they were available on proposed dates before randomization. Nonattendance is common in trials of group interventions for chronic pain, for example, 17% and 11% in 2 similar studies.Although diaries were poorly completed, the findings were consistent with main results. Defining the population of interest is important for trials of interventions of headache disorders. It is also important that criteria developed for evaluating drug treatments for pain are not inappropriately applied to studies on nonpharmacological treatments.The CHESS intervention in the absence of a clinical effect seems to generate additional QALYs and has a high probability of cost-effectiveness given UK cost-effectiveness thresholds. The EQ-5D-5L might be measuring nonspecific effects not captured by the HIT-6 or it might be that the early effect on headache-related disability has had a larger proportional effect in the area under the curve analysis.The control intervention was more than just usual care; the results of the classification interview were fed back to participants and their GPs, which might have reduced any potential effect size from the CHESS intervention if people in the control group used medication more appropriately in light of our feedback. However, the absence of any differences over time in either group in the use of prophylactic medications make it unlikely that improved diagnosis in the control group affected our findings.The trial found no evidence of any clinically relevant benefit from the CHESS intervention across multiple outcomes, at multiple time points, or in any sensitivity or subgroup analyses. It clearly demonstrates the intervention tested here is ineffective and not detrimental. This is surprising because the CHESS intervention targeted the key modifiable psychological variables known to be predictive of poor prognosis in chronic headache disorders, had a solid theoretical underpinning, intervention fidelity was high, and it was well regarded by participants and facilitators.In conclusion, our data effectively exclude the possibility that this short intervention is effective for the treatment of chronic migraine or chronic tension–type headache and episodic migraine. There remains a need to identify more effective treatments for people living with, the sometimes disabling, symptoms of chronic migraine or chronic tension–type headache and episodic migraine. | PMC10065208 |
Study Funding | ARC | This research was funded by the National Institute for Health Research (NIHR) Program Grants for Applied Research program (RP-PG-1212-20,018). S.J. Taylor is supported by the National Institute for Health Research ARC North Thames. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. | PMC10065208 | |
Disclosure | Arthritis, Pain, pain | ARTHRITIS, CHRONIC HEADACHE | M. Underwood reports grants from NIHR during the conduct of the study; personal fees from National Institute for Health Research, grants from National Institute for Health Research, grants from vs Arthritis, other from Multiple professional conferences, grants from Stryker Ltd, grants from SERCO Ltd, other from Confederation for Advanced Research Training in Africa (CARTA), and personal fees from Clinvivo Ltd, outside the submitted work, and is chief investigator on multiple research grants from Australian National Health and Medical Research Council. S. Patel is a coinvestigator on research projects funded by the NIHR. She is the director of a limited company providing pain management and other psychological services. H. Sandhu is a chief investigator and coinvestigator on research projects funded by the NIHR. She is the director of a limited company providing pain management and other psychological services. F. Griffiths reports grants from NIHR during the conduct of the study M.S. Matharu reports grants, personal fees, and honorarium for serving on advisory board from Allergan, honorarium for serving on advisory board from Novartis, personal fees and honorarium for serving on advisory board from Eli Lilly, personal fees and honorarium for serving on advisory board from TEVA, grants from Abbott, grants from Medtronic, grants from electroCore, and personal fees and honorarium for serving on advisory board from Salvia, outside the submitted work; In addition, MSM has a patent WO2018051103A1 issued. S.J.C. Taylor reports grants from HTA Improving the Wellbeing of people with Opioid Treated CHronic pain; I-WOTCH HTA 14/224/04, grants from NIHR PGfAR Competition 14 stage 2 Chronic Headache Education and Self-management Study (CHESS) reference number: RP-PG-1212-20,018, and grants from NIHR Programme Grant Round 3: RP-PG-0707-10,189 “Self-management for Chronic Pain” (COPERS) outside the submitted work. All other authors have nothing to declare. Go to | PMC10065208 |
Authors | PMC10065208 | |||
Glossary | Headache, Depression, Anxiety, Pain | adverse eventsComplier Averaged Causal EffectChronic Headache Education and Self-management Studydefined daily doseHospital Anxiety and Depression ScaleHeadache Impact Test
Pain Self-Efficacy Questionnaireserious AE | PMC10065208 | |
References | PMC10065208 | |||
Objective | To evaluate if daily oral 75 µg of Desogestrel (DSG) for 3 months prior to the insertion of etonogestrel-releasing contraceptive implant (ENG-IMPLANT) might help reduce its premature discontinuation. | PMC10010063 | ||
Results | bleeding | BLEEDING | A total of 66 women were randomized in the ENG-IMPLANT group (26) and in the DSG + ENG-IMPLANT group (40), respectively, in the Geneva University Hospitals and Basel University Hospital, from August 15th, 2016 through September 30th, 2019. In the DSG + ENG-IMPLANT group, patients were given a 3 months’ supply of 75 µg of DSG before the insertion of the ENG-IMPLANT. All women were seen after 3 months for bleeding and satisfaction evaluation, and at 12 months post ENG-IMPLANT insertion. Higher levels of satisfaction at 12-months were found in the ENG-IMPLANT group compared to the DSG + ENG-IMPLANT group (8.5 ± 1.7 vs. 6.6 ± 2.9, p = 0.012). There were no statistically significant differences regarding tolerance (7.8 ± 2.5 vs 6.8 ± 2.6, p = 0.191) and contraceptive continuation (80% vs 72.4%, p = 0.544) between groups. | PMC10010063 |
Supplementary Information | The online version contains supplementary material available at 10.1186/s13104-023-06304-3. | PMC10010063 | ||
Keywords | PMC10010063 | |||
Introduction | abdominal pain, vaginal infection, weight gain, mastodynia, acne, headache | SIDE EFFECT, VAGINAL BLEEDING, VAGINAL INFECTION, ACNE | Etonogestrel-releasing contraceptive implant (ENG-IMPLANT) is a single rod implant containing 68 mg of etonogestrel which is user independent and can be used for three years. Main side effects of ENG-IMPLANT are related to irregular vaginal bleeding. Other side effects such as weight gain, headache, acne, mastodynia, abdominal pain, emotional liability and vaginal infection are less frequent [An approach that would triage women who may have side effects and consequently difficulties adhering to ENG-IMPLANT could decrease premature removal. Such approach could be the use of daily oral 75 µg of Desogestrel (DSG) prior to the insertion of ENG-IMPLANT. In fact, DSG is transformed into its active form, etonogestrel, after hepatic metabolism and a very similar side effect profile has been described between ENG-IMPLANT and DSG users [This prospective randomized study aims to evaluate if the pre-treatment with DSG prior to ENG-IMPLANT insertion (I) increases the continuation rate at one year, if it (II) increases the tolerance of the implant and (III) to compare side effects profile of DSG and ENG-IMPLANT at 3 months. | PMC10010063 |
Main text | PMC10010063 | |||
Materials and methods | PMC10010063 | |||
Setting and study population | vaginal bleeding, gynaecological cancer, metabolic diseases, venous thromboembolism, hypersensitivity, diabetes | VAGINAL BLEEDING, COAGULATION DISORDERS, HEPATIC DISORDER, RECRUITMENT, METABOLIC DISEASES, HYPERTENSION, HYPERSENSITIVITY, DIABETES | Between August 15th, 2016 and September 30th, 2019, we conducted a randomized prospective open-label study of women aged 18 to 42 years who were interested in using ENG-IMPLANT and were willing to have 90 days of pre-treatment with DSG. The study was conducted in the family planning clinic of the Geneva University Hospitals and women’s policlinic of the University Hospital Basel. The exclusion criteria were pregnancy, lactation, vaginal bleeding of unknown origin, wish to become pregnant, weight > 80 kg, history of venous thromboembolism, hypertension, diabetes or other metabolic diseases, coagulation disorders, severe hepatic disorder, history of gynaecological cancer, known hypersensitivity to study drugs and current treatment with enzyme inducing drugs. The study was approved by the ethics committees of both hospitals (CCER 16-972). All patients signed an informed consent prior to recruitment. | PMC10010063 |
Study procedure | bleeding | BLEEDING | Once consent was obtained, women were randomized either to the ENG-IMPLANT group or the DSG + ENG-IMPLANT group. In the ENG-IMPLANT group, the implant was inserted immediately. In the DSG + ENG-IMPLANT group, patients were given a 3 months’ supply of DSG to be started immediately after which insertion of ENG-IMPLANT was proposed. In both groups, patients were instructed to complete a bleeding calendar and a satisfaction questionnaire. A 3-month visit was pre-programmed for all participants, during which the bleeding calendar and the questionnaire were collected. Participants in the DSG + ENG-IMPLANT group who completed the 3 months on DSG pill had their ENG-IMPLANT inserted during this visit. All patients were seen or called over the phone after 12 months post ENG-IMPLANT insertion in both groups. Women who had their implant removed between 3 to 12 months after the insertion completed the satisfaction questionnaire at the time of removal. | PMC10010063 |
Measurement of outcomes and other variables of interest | bleeding, headaches, irregular vaginal bleeding, breast pain, Weight gain | BLEEDING | Socio-demographic characteristics were collected. Data collectors recorded the date of implant insertion or the date of DSG initiation. The main outcome variable for this study was method discontinuation. Secondary outcomes were the side effects, tolerance and satisfaction 3 months after inclusion and 12 months after ENG-IMPLANT insertion.A satisfaction questionnaire and a bleeding calendar was used to assess bleeding patterns throughout the first 3 months of use in both groups. Overall, irregular vaginal bleeding was defined as any deviation from their habitual menstrual patterns of bleeding.The satisfaction questionnaire evaluated side effects on skin, mood, sex-drive, abdomino-pelvic or breast pain, headaches, changes to vaginal discharge, and irregular vaginal bleeding according to a graded 5 points Likert score, from never experiencing (1 point) to all the time experiencing (5 points). Two separate questions evaluated tolerance and satisfaction and were graded on a scale from 0 to 10 (0 not tolerating or unsatisfied with the method and 10 being totally satisfied and perfectly tolerating). Weight gain as cause for removal was noted when relevant. | PMC10010063 |
Randomization and statistical analysis | Statistical analysis was performed using the Stata program version 13 (StataCorp LP: College Station, TX, USA); the significance level for all tests was p < 0.05. To detect a mean difference of 0.5 standard deviation on the numerical tolerance scale, with a power of 0.85 and type 1 error rate of 0.05, we needed 2 groups of 74 participants. The randomization plan was so as to have 33% more participants in the DSG + ENG-IMPLANT group, with a 1:3 ratio, because of 35% drop out in the ENG-IMPLANT group. This would have provided a power of 0.8 to detect a difference in proportions with implant removal of 0.35 versus 0.15 to compensate for possible loss to follow-up. Sample size was set to 80 participants in the ENG-IMPLANT only group, and 120 in the DSG + ENG-IMPLANT group. Randomization was conducted on For continuous variables, means and standard deviation (SD) were calculated; for categorical data, proportions were calculated. The chi-square test and Fisher´s exact test were used when appropriate, as well as the student’s | PMC10010063 | ||
Results | PMC10010063 | |||
Study population | Among the 67 women assessed for eligibility, 66 (98.5%) were included in the study and were allocated either to the ENG-IMPLANT group (26, 39.4%) or the DSG + ENG-IMPLANT group (40, 60.6%) (Fig. Flowchart of study participants | PMC10010063 | ||
Participants' characteristics | Additional file | PMC10010063 | ||
Discussion | PMC10010063 | |||
Findings, their interpretation and comparison to other studies | There have been numerous studies evaluating ENG-IMPLANT side effects but no trial, to our knowledge, who evaluate whether the practice of 3 months oral intake of DSG prior to ENG-IMPLANT insertion improves its continuation rate at-1-year.There was no statistically significant difference regarding overall satisfaction or method continuation when using DSG for 3 months prior to ENG-IMPLANT insertion. Women who tolerated well the DSG pill at 3 months (score > 5) did not seem to better tolerate the implant at 12 months, since the proportion of women reporting good to excellent tolerance at 12 months was lower compared to the ENG-IMPLANT group alone. This might suggest that using DSG in order to predict or improve the continuation rate at one year of ENG-IMPLANT is not a promising strategy.Analysis of side effects reported in both groups did not show a difference in average tolerance between the two groups at 3 and 12 months. However, women reported a higher level of satisfaction in the ENG-IMPLANT group than the DSG + ENG-IMPLANT group at 12 months (8.5 vs. 6.6, p = 0.012). The incidence of side effects with ENG-IMPLANT at 3 and 12 months are congruent with previous publications [The higher level of satisfaction at 12 months in the ENG-IMPLANT group compared with the DSG + ENG-IMPLANT group is probably related to the fact that the study was offered only to patients interested in a long-acting reversible contraception willing to accept the possibility of a randomisation to an initial 3 months period of pill intake. Patients’ self-determination when choosing a contraceptive method has shown to ultimately result in greater satisfaction and higher continuation rates [ | PMC10010063 | ||
Conclusion | In conclusion, although our small sample size, it seems that the use of DSG prior to ENG-IMPLANT insertion does not help in predicting the continuation rate of the implant at one year. | PMC10010063 | ||
Limitations | The main limitation of our study is the small number of patients included and the high rate of loss at follow-up. Therefore, no definitive conclusions can be drawn to enforce change in attitude. | PMC10010063 | ||
Acknowledgements | Not applicable. | PMC10010063 | ||
Author contributions | SC and MY conceived the protocol object of the study. VL and MB executed the literature search and performed the data collection with FT and SG. SC, VL, RC and MY conceived and oversaw the conduction of the study. RC performed data review, methodology and statistical analysis. The manuscript was drafted by VL and critically revised by RC, TS, MV and MY. All authors read and approved the final manuscript. | PMC10010063 | ||
Funding | Funding for DSG and ENG-IMPLANT were provided for the study by MSD Switzerland. | PMC10010063 | ||
Availability of data and materials | According to Institutional Policies the database will be available upon request. | PMC10010063 | ||
Declarations | PMC10010063 | |||
Ethics approval and consent to partcipate | Approved by the Ethics Committee of Geneva on 12.04.2017 (CCER 2016-00972).The trial was retrospectively registered on | PMC10010063 | ||
Consent for publication | All the authors have approved the manuscript for publication. | PMC10010063 | ||
Competing interests | There are no disclosures of interest regarding financial, personal, intellectual, or religious interests. Completed disclosure of interests are available to view online as supporting information. | PMC10010063 | ||
References | PMC10010063 | |||
BACKGROUND: | pain, knee osteoarthritis, KOA | ADVERSE EFFECTS, KNEE OSTEOARTHRITIS | These authors contributed equally to this paper. In the treatment of knee osteoarthritis (KOA), there is a need for the long-term use of therapeutic drugs that reduce joint pain and have fewer adverse effects. | PMC10357135 |
OBJECTIVE: | KOA pain | This study aimed to investigate the therapeutic effect of bean pressing on ear points on early KOA pain. | PMC10357135 | |
METHODS: | KOA | MAY | One hundred patients with KOA recruited at the Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022 were divided randomly into a treatment group ( | PMC10357135 |
RESULTS: | On day 5 following the start of treatment, the visual analog scale (VAS) and WOMAC scores of the treatment group were significantly lower than those of the control group ( | PMC10357135 | ||
CONCLUSIONS: | KOA pain, KOA swelling | Auricular bean-pressing therapy had an analgesic effect and could also alleviate mild to moderate KOA swelling, joint stiffness, and other symptoms, effectively reducing the demand for NSAIDs and improving both knee function and quality of life. The results suggested that auricular bean-pressing therapy has promising prospects in the treatment of early KOA pain. | PMC10357135 | |
Introduction | bone hyperplasia, knee disability, swelling, pain, KOA, Knee osteoarthritis | SEPTIC SYNOVITIS, KNEE OSTEOARTHRITIS, DEGENERATION | Knee osteoarthritis (KOA) is pathologically characterized by cartilage destruction, degeneration, bone hyperplasia, aseptic synovitis, and ligament degeneration. Its clinical manifestations include pain, swelling, and limited mobility, and in severe cases, it may lead to knee disability, which more frequently occurs in middle-aged and elderly people [Auricular point bean pressing involves pressing and fixing cowherb seed on the auricular points to continuously stimulate them and create a therapeutic effect [ | PMC10357135 |
Materials and methods | PMC10357135 | |||
Clinical data | eczema, KOA | MAY, ECZEMA | This was a randomized controlled trial. One hundred participants were selected from patients with KOA who were treated at the Department of Orthopedics of Wenzhou Hospital of Traditional Chinese Medicine between February 2019 and May 2022. The standard follow-up for all treated patients lasted 4 weeks. The study was approved by the ethics committee of the Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine (approval no. WTCM-H-KT-2019047), and all patients provided signed informed consent for their inclusion in the research. The study met the requirements of the Declaration of Helsinki.One hundred patients with KOA enrolled in this study were divided into control and study groups (The inclusion criteria were: (1) patients The exclusion criteria were: (1) patients who had undergone knee surgery, (2) patients who had undergone intra-articular injection treatment within 3 months before the study treatment, (3) patients who could not complete the data collection form, and (4) patients with ear eczema or a history of any ear surgery. | PMC10357135 |
Therapeutic methods | pain | SEPARATION |
Auricular bean-pressing process. (A) Disinfection; (B) Selected auricular acupoints; (C) Fixed Cowherb seeds: (D) Finished.The control group received routine rehabilitation treatment. In both groups, the patients required NSAIDs during treatment and follow-up; this was prescribed as oral celecoxib (Pfizer Inc., USA) as an anti-inflammatory and for pain relief, one tablet twice a day. Functional exercises were prescribed: isometric training, e.g., straight leg raising and plantar dorsiflexion as the main methods for enhancing muscle strength when the pain was severe or in the acute stage. Joint loosening training included femoral-tibial and proximal tibiofibular joint long-axis traction, patellofemoral lateral and up-down sliding, patellofemoral joint separation, lateral horizontal pushing of the femorotibial joint, patella sliding, and knee extension swings [The treatment group received auricular point bean-pressing therapy based on the rehabilitation treatment. For auricular disinfection, a cotton swab was pressed onto the acupoints (Fig. | PMC10357135 |
Treatment indexes | KOA, fasting venous blood, pain | INFLAMMATION, CHRONIC DISEASES | To assess the efficacy of treatment on knee function and pain, the WOMAC index scores [The WOMAC is used mainly to evaluate the degree of KOA in patients. The scale includes three dimensions: pain, stiffness, and joint function, with 24 evaluation items. A five-grade scoring method was adopted, and each item was scored from 0 to 4 points according to severity (maximum score: 96 points). The higher the score, the more serious the condition.The VAS scale comprised a 100-mm-long line with anchoring descriptors. The patient marked the line to indicate their pain perception, and the result was expressed as the distance from the left end point to the marked point (in mm). The maximum score was 10 points. The lower the score, the better the pain relief effect.The CRP level with high sensitivity can provide effective information for many types of chronic diseases, and its value greatly increases in the early stage of inflammation. In the present study, 5 mL of fasting venous blood was collected from the patient in the morning and centrifuged at high speed. Serum was obtained, and the CRP value was detected by radioimmunoassay. | PMC10357135 |
Statistical analysis | We used SPSS™ Statistics v25.0 software (IBM, Chicago, USA) for all data processing. The data with normal or approximately normal distribution were expressed as mean | PMC10357135 | ||
Results | PMC10357135 | |||
General information statistics |
Comparison of general data of patients between two groups
Sample size determination. Notes: The map summarizes the number of the retrospectively selected patients, patients excluded, and the final sample size obtained. Of the 107 patients sampled in this study, 7 did not meet the inclusion criteria, and 3 were excluded based on the above clinical criteria. None of the patients refused to provide informed consent or undergo continued treatment. Follow-up was discontinued for 4 patients for personal reasons (Fig. | PMC10357135 | ||
Comparison of the knee sign scores and C-reactive protein levels between the two groups before and after treatment | tenderness, knee joints, swelling, pain |
Comparison of swelling, tenderness, range of motion, and CRP between the two groups (Compared with the same group before treatment,
Comparison of WOMAC scores between the two groups (Compared with the same group before treatment, After 4 weeks of treatment, the swelling, pain, mobility score, and CRP of the knee joints in the treatment group were significantly lower than those in the control group (all | PMC10357135 | |
Comparison of the Western Ontario and McMaster Universities osteoarthritis scores between the two groups before and after treatment | The comparison of the total WOMAC scores between the two groups before treatment was not statistically significant (After 4 weeks of treatment, the NSAID requirement of the treatment group was significantly lower than that of the control group (Fig.
The numbers of patients not requiring celecoxib treatment in both treatment group and control group. | PMC10357135 | ||
Discussion | obesity, osteoarthritis, meniscus rupture, KOA, disability, periarticular fractures, KOA swelling, injuries | OBESITY, OSTEOARTHRITIS, JOINT DISEASES, DEGENERATIVE JOINT DISEASE, SECONDARY, PATHOGENESIS, COMPLICATIONS, CHRONIC DISEASE | In the present study, the VAS and WOMAC scores of the treatment group were significantly lower than those of the control group, demonstrating that auricular bean-pressing therapy possessed analgesic and discomfort relief effects, for example, relieving mild- to moderate-degree KOA swelling, joint stiffness, and other symptoms. Considerable evidence has demonstrated the analgesic effect of auricular point bean-pressing therapy [The pathogenesis of KOA, a degenerative joint disease, remains unclear. It may be related to age, obesity, genetics, and other factors and can be secondary to joint injuries or joint diseases, such as meniscus rupture, joint deformity, and periarticular fractures [Of note, the results of the present study showed that after 28 days of intervention, the number of people in the treatment group who needed to take celecoxib was significantly lower than that of the control group, and the difference was statistically significant. The dependence on NSAIDs and related complications was also effectively improved after auricular bean-pressing therapy.A slow, progressive, and chronic disease, osteoarthritis is the leading cause of disability among elderly people. Existing studies showed that many cytokines, growth factors [Auricular point bean-pressing therapy has the potential to treat KOA [Cowherb seed is a well-known TCM herb and is listed in the The small sample size of the present single-center study may have led to some error in the experimental results. Additionally, the short follow-up period in the present study made it difficult to determine the long-term effects of auricular bean pressing on patients with KOA. Further research should be undertaken without these limitations. | PMC10357135 |
Conclusion | KOA pain, knee pain | ADVERSE REACTIONS | The present study demonstrated that compared with conventional rehabilitation, auricular point bean-pressing therapy combined with conventional rehabilitation treatment can further relieve knee pain, improve patients’ knee function, and reduce the demand for NSAIDs. This reduces adverse reactions caused by taking drugs, indicating that auricular point bean-pressing therapy combined with conventional rehabilitation treatment could be an effective strategy in treating KOA pain. | PMC10357135 |
Ethical approval | The study was conducted in accordance with the Declaration of Helsinki (as was revised in 2013). The study was approved by the ethics committee of the Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine (approval no. WTCM-H-KT-2019047). | PMC10357135 | ||
Funding | The study was supported by Wenzhou Basic Scientific Research Projects (No. Y20190732). | PMC10357135 | ||
Informed consent | All patients provided signed informed consent for their inclusion in the research. | PMC10357135 | ||
Author contributions | Conception and design of the research: Yeyan Lin, Xuelai Zhou.Acquisition of data: Yeyan Lin, Bin Shen.Analysis and interpretation of the data: Yeyan Lin, Cunxian Lv.Statistical analysis: Yeyan Lin, Yongqin Wu.Obtaining financing: Xuelai Zhou.Writing of the manuscript: Yeyan Lin.Critical revision of the manuscript for intellectual content: Yeyan Lin.All authors read and approved the final draft. | PMC10357135 | ||
Acknowledgments | The authors are particularly grateful to everyone who helped them with the article. | PMC10357135 | ||
Conflict of interest | The authors declare that they have no competing interests. | PMC10357135 | ||
References | PMC10357135 | |||
Objectives | OSA | OBSTRUCTIVE SLEEP APNEA | To compare the effects of two types of titratable mandibular advancement devices (MADs), namely MAD-H (allowing limited vertical opening) and MAD-S (allowing free vertical opening), on respiratory parameters and upper airway dimensions in patients with mild to moderate obstructive sleep apnea (OSA). | PMC10160211 |
Materials and methods | OSA, apnea | Patients with mild to moderate OSA (5 ≤ apnea–hypopnea index (AHI) < 30 /h) were randomly assigned to two parallel MAD groups. All MADs were subjectively titrated according to a standardized protocol during a 3-month follow-up. Every patient underwent two polysomnographic recordings, and two cone beam computed tomography scans in supine position: one at baseline and another one after 3 months with the MAD in situ. The primary outcome variables were the AHI in supine position (AHI-supine) and the minimal cross-sectional area of the upper airway in supine position (CSAmin-supine). | PMC10160211 | |
Results | A total of 49 patients were recruited, and 31 patients (21 men and 10 women) with a mean (± SD) age of 48.5 (± 13.9) years and a mean AHI of 16.6 (± 6.7) /h completed the study. In the per-protocol analysis, there was no significant difference between MAD-H ( | PMC10160211 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.