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Conclusions
FM loss, weight loss, T2DM
In contrast with other interventions geared toward weight loss where behavioral and physiological changes in NEPA and NEAT, respectively, may be expected, a more conservative and ecological 1-year exercise intervention for individuals with T2DM had no impact on NEPA and estimated NEAT on the non-exercise days, regardle...
PMC10063485
Acknowledgements
The authors are grateful to all participants for their time and effort.
PMC10063485
Author’s contribution
IRC contributed to methodology, formal analysis, and writing—original draft; MHR contributed to formal analysis and writing—original draft; JPM contributed to conceptualization, methodology, formal analysis, and writing—original draft; PBJ contributed to methodology and writing—review and editing; GBR contributed to wr...
PMC10063485
Funding
Open access funding provided by FCT|FCCN (b-on). This work was conducted at the Interdisciplinary Center for the Study of Human Performance (CIPER), unit I&D 447 (UIDB/00447/2020), Faculty of Human Kinetics of the University of Lisbon, and supported by the Portuguese Foundation for Science and Technology, the Portugues...
PMC10063485
Data availability statement
The datasets used during the current intervention are available from the corresponding author on reasonable request.
PMC10063485
Declarations
PMC10063485
Conflict of interest
The authors report there are no conflicts of interest to declare.
PMC10063485
Ethical standard statement
The study was approved by the Ethics Council of the Associação Protetora dos Diabéticos de Portugal (Approval Number: 07/17/2013) and conducted in accordance with the Declaration of Helsinki for Human Studies [
PMC10063485
Informed consent
Written informed consent was obtained from all participants before proceeding with any protocol-specific procedures.
PMC10063485
References
PMC10063485
Background:
depression, post-PCI angina, angina, anxiety
Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches t...
PMC10101135
Methods:
Angina, post-PCI angina
Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life–5 dimension–5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was pe...
PMC10101135
Results:
myocardial infarction, angina
ATRIAL FIBRILLATION, MYOCARDIAL INFARCTION
Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59,
PMC10101135
Conclusions:
angina, less angina
Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriatene...
PMC10101135
Registration:
URL:
PMC10101135
What is Known
depression, Angina, angina, anxiety
RECURRENCE
Angina after percutaneous coronary intervention (PCI) is associated with long-term anxiety, depression, and impairment of both physical function and quality of life.Persistence or recurrence of angina after PCI may affect 20% to 40% of patients during short-to-medium-term follow-up.
PMC10101135
What the Study Adds
Angina, angina, anxiety, angina post-PCI.The, pre-PCI, post-PCI angina, depression
DISEASE
Patients with post-PCI angina reported more frequent angina and poorer quality of life at baseline yet had physiologically less severe disease and, accordingly, tended to achieve less improvement in coronary physiology metrics than those who were free from angina post-PCI.The degree of improvement in patient-reported o...
PMC10101135
Methods
The data that support the findings of this study are available from the corresponding author upon reasonable request. The rationale, study design, and primary outcome of the TARGET-FFR controlled trial have been published previously.
PMC10101135
Definition of Angina
angina
The presence of angina post-PCI was defined by a patient-reported follow-up SAQ-angina frequency (SAQ-AF) score of <100. Patients with a follow-up of SAQ-AF score=100 were classified as having no angina.
PMC10101135
Clinical Outcomes
vessel failure, vessel myocardial infarction, cardiovascular death
Clinical outcomes at a median of 3 years post-PCI were assessed by electronic health record linkage. The primary clinical outcome was target vessel failure, a composite end point comprising cardiovascular death, target vessel myocardial infarction, and target vessel revascularization.
PMC10101135
Statistical Analysis
Continuous variables are presented as mean±SD and categorical data as counts and percentages. A 2-sample
PMC10101135
Results
angina, post-PCI angina
Of 260 participants, 230 (88.5%) provided follow-up SAQ-AF scores 3 months (median [interquartile range], 105 [31] days) post-PCI. For the purposes of this analysis, patients were stratified by the presence of post-PCI angina. Eighty-eight (38.3%) of 230 patients had post-PCI angina as determined by a follow-up SAQ-AF ...
PMC10101135
Baseline Demographics
Clinical characteristics at baseline are presented in Table Baseline Clinical Characteristics Stratified by Presence of Angina 3 Months Post-PCI
PMC10101135
Procedural Outcomes
Procedural and coronary physiology characteristics are presented in Table Procedural and Coronary Physiology Characteristics Stratified by Presence of Angina 3 Months Post-PCI
PMC10101135
Predictors of Post-PCI Angina
Post-PCI Angina, post-PCI angina
Univariate and multivariate analysis of predictors of post-PCI angina are presented in Table Predictors of Post-PCI Angina
PMC10101135
Clinical Outcomes
vessel failure, post-PCI angina
The rate of target vessel failure at a median (interquartile range) follow-up of 3 (0.9) years was 1.7% (4/230) with no significant difference between groups (no angina, 0.7% versus post-PCI angina, 3.4%;
PMC10101135
Discussion
chest tightness, angina, physician-adjudicated angina, dyspnea, chest pain, post-PCI angina, atrial fibrillation, heart failure
MYOCARDIAL INFARCTION, ANGINAL ATTACKS, ATRIAL FIBRILLATION, HEART FAILURE, HYPERTENSION
One in 3 patients in the TARGET-FFR randomized trial reported angina 3 months after undergoing PCI which, while a substantial proportion, is not unprecedented. In the ABSORB IV trial, 39% (494/1265) of patients in the drug-eluting stent arm had physician-adjudicated angina or angina-equivalent symptoms at 1-year follow...
PMC10101135
Procedural and Intracoronary Physiology Characteristics
Angioplasty, angina, pre-PCI, Coronary microvascular dysfunction, Post-PCI, post-PCI angina, coronary artery disease
STABLE ANGINA, CORONARY ARTERY DISEASE, CORONARY MICROVASCULAR DYSFUNCTION
There were no significant differences between groups in angiography-based parameters of coronary artery disease severity either pre- or post-PCI. Counterintuitively, patients with post-PCI angina had a higher burden of angina at baseline yet physiologically less severe lesions (significantly higher pre-PCI FFR and CFR ...
PMC10101135
Limitations
vessel failure
TARGET-FFR was a single-center study with a relatively homogeneous PCI practice, including high rates of lesion predilatation and high-pressure stent postdilatation. A larger multicenter trial incorporating a wider range of PCI strategies and techniques may have had a different outcome. The study was not powered for cl...
PMC10101135
Conclusions
angina, post-PCI angina
The magnitude of FFR improvement following PCI correlated with angina status and quality of life at follow-up and was an independent predictor of the presence of post-PCI angina. In patients with stable symptoms, intracoronary physiology assessment can aid prediction of angina relief and quality of life improvement aft...
PMC10101135
Article Information
PMC10101135
Sources of Funding
HEART
Endowment funds at the Golden Jubilee National Hospital (NHS Golden Jubilee), Glasgow, United Kingdom, with support from the British Heart Foundation (Research Excellence Award RE/18/6/34217).
PMC10101135
Disclosures
MAY, COLLET
Dr Collison received consultancy fees from Abbott. Dr Mizukami received consultancy fees from Zeon Medical Inc; research grants from Boston Scientific; speaker fees from Abbott, Cathworks, Boston Scientific. Dr Collet received research grants from Biosensors, Coroventis Research, Medis Medical Imaging, Pie Medical Imag...
PMC10101135
Supplemental Material
Supplemental MethodsFigure S1Tables S1–S13
PMC10101135
Supplementary Material
PMC10101135
Nonstandard Abbreviations and Acronyms
Canadian Cardiovascular Societycoronary flow reserveEuropean quality of life-5 dimension-5 level questionnairefractional flow reservepercutaneous coronary interventionSeattle Angina QuestionnaireSeattle Angina Questionnaire-angina frequencyFor Sources of Funding and Disclosures, see page 164.Supplemental Material is av...
PMC10101135
References
PMC10101135
Background
Hypertension
HYPERTENSION
Clinical trials commonly use multiple endpoints to measure the impact of an intervention. While this improves the comprehensiveness of outcomes, it can make trial results difficult to interpret. We examined the impact of integrating patient weights into a composite endpoint on the interpretation of Control of Hypertens...
PMC9906819
Methods
PREGNANCY HYPERTENSION
Outcome weights were extracted from a previous patient preferences study in pregnancy hypertension (Outcome weights from the preference subgroups were integrated with CHIPS data for the seven outcomes identified in the preference study. A weighted composite score was derived for each participant by multiplying the pref...
PMC9906819
Results
Composite scores were similar between trial arms with the use of equal weights or those of subgroup (1) (95% confidence intervals [CIs]: − 0.03, 0.02;
PMC9906819
Conclusions
Evidence-based recommendations for ‘tight’ control are consistent with most women’s preferences, but for a sixth of women, ‘less-tight’ control is more preference consistent. Depending on patient preferences, a single trial may support different interventions. Future trials should specify component weights to improve i...
PMC9906819
Trial registration
ClinicalTrials.gov NCT01192412
PMC9906819
Supplementary Information
The online version contains supplementary material available at 10.1186/s13063-023-07118-1.
PMC9906819
Keywords
PMC9906819
Introduction
Hypertension
SECONDARY, HYPERTENSION
Clinical trials in cardiovascular medicine routinely use primary, secondary, and other endpoints to capture the breadth of an intervention’s effects. However, this can make the interpretation of trial results challenging, as an intervention’s effects can vary by outcome, including benefits and harms [The international ...
PMC9906819
Discussion
BWS
PRETERM BIRTH, PREGNANCY HYPERTENSION
This re-analysis of CHIPS trial outcomes incorporated patient views and demonstrated that integrating patient preferences for outcomes and their associated weights into trial analyses is feasible and can identify different management approaches based on the results of a single trial. Our findings suggest that while alm...
PMC9906819
Conclusions
This study illustrates that integrating patient values into trial analyses can change the interpretation of trial results for clinical decision-making. Future trials with composite or multiple outcomes should seek patient preference weights to improve the interpretation of trial results and support patient-centred care...
PMC9906819
Acknowledgements
We would like to acknowledge the time and contributions of the 981 participants in the CHIPS trial and the 183 participants in the preferences study that made this work possible, as well as the members of the CHIPS Study Group (Additional file
PMC9906819
Authors’ contributions
MH, NB
All authors contributed to the conceptualization and design of the study, have approved the submitted final version and have agreed to be accountable for their own contributions and the work as a whole. In addition, RKM contributed to the acquisition, analysis, and interpretation of the data and drafted the initial man...
PMC9906819
Funding
This study was funded by peer-reviewed grants from two government entities: the Canadian Institutes of Health Research (MCT 87522) and the BC SUPPORT Unit (RWCT-001). Funders had no involvement in the design of the study; the collection, analysis and interpretation of the data; or the presentation of findings.
PMC9906819
Availability of data and materials
APPENDIX
The datasets used and/or analysed during the current study are not publicly posted as participant consent was not obtained for the open distribution of data. However, data are available from the corresponding author upon reasonable request. Aggregate data are available as part of the Supplementary Appendix of the initi...
PMC9906819
Declarations
PMC9906819
Ethics approval and consent to participate
This study was reviewed and approved by the Behavioural Research Ethics Board (H17-01194) at the University of British Columbia.
PMC9906819
Consent for publication
Not applicable
PMC9906819
Competing interests
The authors declare that they have no competing interests.
PMC9906819
References
PMC9906819
Background
Residual neuromuscular block
COMPLICATION
Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear.
PMC10413529
Objectives
cisatracurium-induced neuromuscular block
To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block.
PMC10413529
Methods
A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end o...
PMC10413529
Results
The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257,
PMC10413529
Conclusions
Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice.
PMC10413529
Trial registration
this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).
PMC10413529
Keywords
PMC10413529
Background
MUSCLE RELAXATION, POSTOPERATIVE COMPLICATIONS
Neuromuscular blocking agents (NMBAs) are widely used to provide muscle relaxation for endotracheal intubation, certain modes of mechanical ventilation and surgical procedures. However, with the widespread application of neuromuscular blocking agents in general anesthesia, the residual effects have become one of the im...
PMC10413529
Methods
PMC10413529
Study design and patient selection
Neuromuscular block
NEUROMUSCULAR BLOCK
This study was approved by the Ethics Committee of the Third Xiangya Hospital. Written informed consent was obtained from all patients. Inclusion criteria were: aged 60 to 85 years, American Society of Anesthesiology (ASA) physical status 1 to 3, and scheduled for elective surgery under general anesthesia with cisatrac...
PMC10413529
Procedure
nausea and vomiting, normocapnia, postoperative pain, tetanic
MUSCLE RELAXATION
On arrival at the operating room, an intravenous cannula was inserted in the forearm vein of the patient, and standard anesthesia monitoring (noninvasive blood pressure, electrocardiogram, and oxygen saturation) were established and anesthesia depth was monitored using Bispectral Index (BIS, Medtronic, Minneapolis, MN,...
PMC10413529
Statistical analysis
A sample size was calculated based on the primary outcome variable (the time from the administration of neostigmine to a TOF ratio of 0.9). To achieve a power of 0.8 with an alpha level of 0.05 and an effect size of f = 0.25, and considering a 10% drop out rate, a total sample size of N = 200 was needed. SPSS 22.0 soft...
PMC10413529
Results
allergies
ALLERGIES
From January 2022 to November 2022, 240 ASA I-III patients aged from 60 to 85 who were scheduled for elective non-cardiac surgery under general anesthesia were enrolled, of which 40 patients were excluded due to contraindications (n = 18), allergies (n = 12) or declined to participate (n = 10). 200 patients completed r...
PMC10413529
Comparison of general data and perioperative data between the groups
Table  Analysis of baseline characteristicsBMI: Body Mass Index
PMC10413529
Comparison of results of postoperative muscle relaxation monitoring
Postoperative nausea and vomiting
MUSCLE RELAXATION
As listed in Table Similar to the results of time to reach TOF value of 0.9, TOF value at 10 min after administration in 20 µg, 40 and 50 µg groups was significantly increased compared with that in control group (H = 93.351, In addition, we evaluated the postoperative outcomes of each group. As shown in the Table  Anal...
PMC10413529
Discussion
postoperative cognitive impairment, muscle blockade
DEGENERATION, MUSCLE RELAXATION, NEUROMUSCULAR BLOCKADE, POSTOPERATIVE COMPLICATIONS, COMPLICATION
This study explored the optimal dose of neostigmine in elderly patients to reverse the TOF value to 0.9. The results indicated that the dose of 40 µg/kg may be an optimized choice and did not increase the incidence of postoperative cognitive impairment or PONV.Incomplete neuromuscular recovery after general anesthesia ...
PMC10413529
Author contributions
Yan Liao and Jianbin Tong designed the study and collected the data. Mengya Cao, Yangwen Ou analyzed the data and Huifan Huang, Yan Liao drafted the manuscript. Mengya Cao and Jianbin Tong provided critical feedback on the study design, data analysis, and manuscript revisions.All authors have read and approved the fina...
PMC10413529
Funding
Not applicable.
PMC10413529
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10413529
Declarations
PMC10413529
Ethics approval and consent to participate
The study was approved by the ethics committee of the Ethics Committee of the Third Xiangya Hospital (reference number [R22008]) and written informed consent was obtained from all participants. The authors declare that all experiments were performed in accordance with relevant guidelines and regulations (such as the De...
PMC10413529
Consent for publication
Not applicable.
PMC10413529
Competing interests
The authors declare that they have no competing interests.
PMC10413529
References
PMC10413529
Background
DEL
Edited by: Mario Clerici, University of Milan, ItalyReviewed by: Camilla Tincati, University of Milan, Italy; Julian Olalla, Hospital Costa del Sol, SpainThe aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug r...
PMC10613634
Methods
BLOOD, SECONDARY
An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio ...
PMC10613634
Results
Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm–time interaction p-value = 0.02) and to a lesser extent for the correspon...
PMC10613634
Conclusion
No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted t...
PMC10613634
Clinical Trial Registration
PMC10613634
Introduction
HIV-1 infection, viremia, virological failure
HIV-1 INFECTION, CHRONIC INFLAMMATION, VIREMIA
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a guideline-recommended regimen for the treatment of HIV-1 infection in both naïve and experienced patients that demonstrated high efficacy and barrier to resistance without occurrence of incident resistance among individuals experiencing virological failure ...
PMC10613634
Methods
INFECTIOUS DISEASE
This is an open-label, prospective, single-center, randomized trial enrolling PLWH seen for care at the Infectious Disease Clinic of Azienda Ospedaliero-Universitaria Policlinico of Modena, Italy. The study, with EudraCT Number 2018-003458-26, was approved by the local Ethical Committee with Authorization Number AOU 00...
PMC10613634
Outcomes
inflammation
INFLAMMATION, SECONDARY
The primary outcome of the trial was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio from enrolment to week 48.The secondary outcomes were the changes in inflammation and other immune characteristics (phenotype of T cells, proportion of cells belonging to different CD4+ and CD8+ T-cell subsets, monocytes, an...
PMC10613634
Immunological analyses
Immunological analyses are described in detail in Supplementary Annex 2 (
PMC10613634
Statistical analyses
AIDS
AIDS
Participants’ characteristics by study arm were described and reported as the number of participants with relative frequencies for categorical factors and as the median and interquartile range (IQR) for continuous variables.Repeated measurements of all biomarkers were available at the three fixed time points (T0 = base...
PMC10613634
Sample size calculations
We based the sample size calculations on the primary outcome change in CD8 count from T0 to T12. At the time of writing the trial protocol, we hypothesized that switching to DTG/3TC could be associated with a higher CD8 activation compared to switching to B/F/TAF. In particular, on the basis of data previously publishe...
PMC10613634
Results
AIDS, high-density lipoprotein
INFECTIOUS DISEASES, AIDS
Between September 2020 and January 2021, 66 patients attending the Clinic of Infectious Diseases of the Azienda Ospedaliero-Universitaria Policlinico of Modena were enrolled in the trial. Epidemiological characteristics are described in Main characteristics of target population by study arm.IQR, interquartile range; MS...
PMC10613634
Primary outcomes: CD4+ or CD8+ T-cell count and CD4/CD8 ratio
Concerning the primary endpoint of absolute values and change in CD4+ or CD8+ T lymphocyte count and in CD4/CD8 ratio, no evidence for a difference by study arm was found either at 6 (T6) or at 12 months (T12) after the switch (T0). All these three main immunological parameters tended to remain stable over time in both...
PMC10613634
CD4+ T-cell subsets
In contrast, when we looked at the proportion of CD4+ T-cell subsets, significant differences in trends by arm were detected for both TM and EMRA (arm–time interaction p-value = 0.02 in the adjusted analysis). The significance was likely to be driven by the trends at T6, the time at which values of both TM (−4.6 cells/...
PMC10613634
CD8+ T-cell subsets
The results for the CD8+ T-cell subsets were similar to those seen for the corresponding CD4+ T cells shown above, although none of the statistical interaction tests reached statistical significance (p = 0.09 for TM and p = 0.19 for EMRA in the adjusted analysis, CD8 subsets by study arm—adjusted analysis. RCT, random...
PMC10613634
Monocytes
We then investigated trend in monocytes, specifically by distinguishing between classical and non-classical subsets (note that non-classical monocytes also included a small proportion of intermediate monocytes). Although no statistical significance was detected for the classical monocyte subsets (interaction p-value=0....
PMC10613634
Inflammation: IL-6
inflammation
INFLAMMATION
We finally analyzed the trend in IL-6, chosen as the most important cytokine related to onset and maintenance of inflammation. Because of the trend seen with the CD4+ and CD8+ TM/EMRA T cell subsets (large difference by study arm at T6 followed by an attenuation of the difference at T12), we hypothesized that this migh...
PMC10613634
Discussion
inflammation, atherosclerosis, HIV infection, non-AIDS
HIV INFECTION, INFLAMMATION, DYSFUNCTION, EVENTS, ATHEROSCLEROSIS, PERSISTENT INFLAMMATION, ENDOTHELIAL DYSFUNCTION
Our randomized study shows no evidence for a difference in absolute CD4+ and CD8+ T-cell counts and in CD4/CD8 ratio trajectories over 12 months of follow-up by study arm (DTG/3TC However, importantly, our data provide additional insights concerning immunological changes after switching from 3DR treatment to DTG/3TC or...
PMC10613634
Author’s note
Preliminary results were presented at the 30th HIV Glasgow, October 23–26, 2022. Abstract n. P099 published in
PMC10613634
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
PMC10613634