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Results | PMC10196888 | |||
Overview | The number of preschools and mother-child dyads participating in the | PMC10196888 | ||
Discussion | PMC10196888 | |||
Principal Findings | MINOR | This trial investigated the effect of the On the basis of GLMM, significant reduction in children’s screen time was observed in the intervention group as compared with the waitlist control group. Our findings are consistent with previous studies [In this study, the baseline screen time reported among children was twice as high as that reported in previous studies [Previously published studies of screen time reduction did not include any parental knowledge component, even though they might have been involved in the intervention. Increasing parental knowledge is the necessary first step for parents to initiate the subsequent actions to reduce their child’s screen time, such as restrictive viewing and supervision. In this study, the mother’s knowledge scores were significantly increased in the intervention group, indicating the importance of improving knowledge in interventions that aim for behavior change. However, improved knowledge alone is insufficient to produce screen time behavior change [In this study, we also found that mothers’ perception about the influence of screen time on their child’s well-being had significant group and time interaction. Our findings were consistent with previous observations in which parental perception about the necessity to limit a child’s screen time resulted in significantly less screen time among preschool children [Compared with a previous study, the A compelling finding from a recent study showed that Malaysian parents found it difficult to incorporate the reading culture into the daily lives of children [Next, the self-efficacy to increase physical activity among mothers was significantly high in the intervention group, albeit with just minor increase in mean scores. According to the observational learning construct, children are highly influenced by their parents’ uptake of physical activity. Thus, future interventions should promote physical activity for the whole family as compared with focusing solely on children. The minor increase in mean scores could be explained by the challenges for mothers to engage their children in physical activity outside the house owing to MCO during the pandemic. A systematic review found significant increase in self-efficacy to increase physical activity when interventions were conducted face to face and objective measures of physical activity accompanied by self-monitoring and performance feedback were reported [In addition, mothers in the intervention group showed significant reduction in leisure screen time by 70 minutes per day. Although most studies of child’s screen time stressed the importance of reducing parental screen time, there is a lack of RCTs that examine the actual reduction. Nevertheless, an RCT using mobile technology to control screen time among adults reported large reduction of 130 minutes within 2 weeks of intervention [In addition, the presence of digital devices in the child’s bedroom has been strongly associated with excessive screen time [ | PMC10196888 | |
Strengths and Limitations | This is one of the pioneer studies that provided strong evidence of the effectiveness of a digitally delivered screen time reduction intervention for parents of preschool children. Furthermore, the intervention also measured self-efficacy as a principal construct of the SCT, thus affirming its use in screen time studies. Low attrition rates indicated strong interest among participants in the reduction of screen time among their children. Furthermore, the use of whiteboard animation videos for health education resonates with young mothers who were mainly millennials, that is, Generation Z. Moreover, the remote method of delivery allowed mothers to conveniently access the intervention at a time and place suitable for them.Nevertheless, this study has few limitations. First, the findings need to be interpreted with caution owing to the limited generalizability. Although the use of screen media diaries helped to minimize recall bias, self-reporting by mothers could have been influenced by social desirability related to underreporting their child’s screen time and overembellishing their parenting capabilities, thus raising issues about the fidelity of the outcomes. Second, owing to the remote method of health education delivery, the lack of physical interaction could have resulted in poor interpersonal relationship between the researcher and the participants, indirectly affecting the strength of the outcomes. Furthermore, we were unable to measure the exact amount of physical activity because outdoor activities were not possible during the pandemic. In addition, data collection for both postintervention time points was also subjected to different conditions as compared with that at the baseline owing to the closure of schools during MCO. During the baseline period and 1-month data collection period, children were undergoing web-based school sessions for 1 hour per day, thus leading to long period of participation in screen-based activities at home. However, during the 3-month postintervention data collection period, physical lessons had resumed for all schools, leaving the children with less time to spend on screen-based activities. Finally, we were unable to explicitly verify whether all mothers watched the given videos, as the number of views could have represented repeated viewing from the same participants. | PMC10196888 | ||
Abbreviations | Consolidated Standards of Reporting Trialsgeneralized linear mixed modelintracorrelation coefficientmovement control orderrandomized controlled trialSocial Cognitive Theory | PMC10196888 | ||
Data Availability | The data sets generated and analyzed during this study are available from the corresponding author upon reasonable request. | PMC10196888 | ||
Abstract | PMC10032296 | |||
Background | psychotic symptoms, treatment-resistant depression, psychosis | “Dissociation” comprises distinct phenomena, some of which are associated with esketamine treatment and some may overlap with positive symptoms of psychosis. Relationships between dissociation and psychotic symptoms assessed by clinician report vs conventional rating scales were investigated in a post hoc analysis of data from the initial treatment session in an open-label, long-term safety, phase 3 study of esketamine plus a newly initiated oral antidepressant in patients with treatment-resistant depression. | PMC10032296 | |
Methods | psychosis | REGRESSION, ADVERSE EVENT, ADVERSE EVENT | Adverse events of dissociation or psychosis were examined via investigator report and the Clinician Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale-Plus, respectively, 40 minutes post first esketamine dose. The range of CADSS total scores associated with investigator-reported severity of dissociation was determined by equipercentile linking. Logistic regression models and receiver operating curve analysis explored the CADSS cutoff point for determining presence/absence of dissociation. Frequency of response to specific CADSS items was examined to investigate qualitative differences in the pattern of symptoms reported across investigator-reported levels of adverse event severity. | PMC10032296 |
Results | Hallucinations, investigator-reported, delusions | ADVERSE EVENTS, EVENTS, ADVERSE EVENT | Dissociation was reported as an adverse event in 14.3% (109/764) of patients. Severity of most CADSS items increased with the severity of investigator-reported dissociation. No CADSS cutoff point discriminated well between the presence and absence of dissociation events. Hallucinations were reported as adverse events in 5 patients; none reported delusions. | PMC10032296 |
Conclusions | psychotic symptoms | ADVERSE EVENTS | CADSS scores and severity of dissociation adverse events move generally in the same direction; however, there is substantial variability in this relationship. No signature profile of dissociative experiences was revealed, and psychotic symptoms were uncommon. | PMC10032296 |
Trial Registration | Clinical Trials.gov identifier: NCT02497287 | PMC10032296 | ||
Significance Statement | TRD, investigator-reported, treatment-resistant depression, delusions, Hallucinations, psychotic symptoms | ADVERSE EVENTS, EVENTS, ADVERSE EVENT | Transient dissociation has been reported with esketamine treatment. Results of a post hoc analysis presented here further characterize the nature and severity of dissociation reported in an open-label phase 3 study (SUSTAIN-2) of esketamine plus a newly initiated oral antidepressant in participants with treatment-resistant depression (TRD). After the first esketamine dose, dissociation was reported as an adverse event in 14.3% (109/764) of patients. Investigators characterized most dissociation events as mild (n = 78), some as moderate (n = 26), and few (n = 5) as severe. Severity of most items of the Clinician Administered Dissociative States Scale (CADSS) increased with the severity of investigator-reported dissociation events. No CADSS cutoff point discriminated well between the presence and absence of investigator-reported dissociation adverse events. Hallucinations or delusions were reported as adverse events in 5 and 0 patients, respectively. In summary, no signature profile of dissociative experiences was revealed, and psychotic symptoms were uncommon. | PMC10032296 |
INTRODUCTION | Clinician-Administered, Treatment-emergent adverse, psychosis, psychotic symptoms, psychotic disorders | ADVERSE EVENT | Dissociation is a clinical construct that incorporates a variety of different types of symptoms, ranging from disturbances in perception of sensory, proprioceptive, or temporal information to disturbances in one’s sense of self or identity. The extent to which the nature of these dissociative experiences is consistent across different clinical conditions or diagnoses has received relatively little attention. For instance, a recent meta-analysis of clinical and nonclinical samples examining the relationship between dissociation and psychotic symptoms in patients with psychotic disorders found a “robust” relationship between dissociative experiences and multiple positive psychotic symptoms but less consistent relationships with negative symptoms (The patterns of dissociation-related symptoms that occur in association with i.v. ketamine treatment as quantified by the Clinician-Administered Dissociative States Scale (CADSS) have been described by multiple groups (It has also been reported that the correspondence between a clinician’s perception of dissociation occurring as an adverse event vs dissociation as characterized by structured measurements (e.g., the CADSS) may vary (Treatment-emergent adverse events, including dissociation and psychosis, were monitored and recorded in the pivotal registration trials of esketamine, thereby providing the opportunity to evaluate the relationship between these (i.e., between patient experience and clinician-reported assessment) as well as adverse event reports of dissociation or psychosis. We thus conducted post hoc analyses of data from the SUSTAIN-2 study ( | PMC10032296 |
MATERIALS AND METHODS | PMC10032296 | |||
Ethical Practices | An independent review board/ethics committees approved the SUSTAIN-2 protocol at each study site, and written informed consent was obtained from all patients before they were enrolled in the study. SUSTAIN-2 is registered at clinicaltrials.gov (identifier: NCT02497287). Study methods pertaining to the work reported herein are summarized below. | PMC10032296 | ||
Patients | MDD, psychotic, DSM-5 | SUSTAIN-2 enrolled adults (≥18 years old) with a diagnosis of recurrent MDD or single episode (≥2 years) MDD without psychotic features per DSM-5 criteria ( | PMC10032296 | |
Study Design | TRD | SUSTAIN-2 was a global, open-label, multicenter, phase 3 study of TRD that evaluated the safety and tolerability of esketamine plus a newly initiated oral antidepressant for up to 1 year ( | PMC10032296 | |
Study Drug | During the induction phase, patients self-administered esketamine nasal spray twice a week for 4 weeks as a flexible-dose regimen, beginning at 28 mg (in those aged ≥65 years) or 56 mg. Subsequent doses could be adjusted (<65 years: 56 or 84 mg; ≥65 years: 28, 56, or 84 mg) based on efficacy and tolerability. All patients were also taking a newly initiated oral antidepressant (i.e., duloxetine, escitalopram, sertraline, or venlafaxine extended release). | PMC10032296 | ||
Safety Assessments | dissociative symptoms, auditory and visual disturbances, Dissociative, psychotic symptoms, heaviness | ADVERSE EVENT, ADVERSE EVENT | Adverse events were monitored throughout the study. Dissociative and positive psychotic symptoms, respectively, were assessed pre-dose and 40 and 90 minutes post-dose using the CADSS (Adverse events were also assessed based on investigator report. The SUSTAIN-2 protocol specified that any untoward medical occurrence that was new in onset or increased in severity following treatment initiation should be reported as a treatment-emergent adverse event. The protocol did not provide investigators with specific guidance of what symptoms constitute an adverse event of dissociation or how/when dissociation as an adverse event should be reported.Dissociation is a unique preferred term in the Medical Dictionary for Regulatory Activities dictionary, and most site investigators reported “dissociation, dissociative symptoms” as adverse event terms that are coded to the preferred term “dissociation.” However, site investigators also reported other terms to describe dissociative symptoms that have been coded to “dissociation” per instruction from the Food and Drug Administration, such as symptoms of auditory and visual disturbances, illusion, feeling abnormal (feeling of floating, flying, falling, detached, heaviness, lightness, etc.), and dreamy state. While potentially allowing for the possibility of increased between-site variability, this approach could be argued to provide a more generalizable picture of what may be happening across a variety of treatment settings, wherein one would not expect the level of standardization of adverse event reporting obtained by using structured psychometric instruments. | PMC10032296 |
Statistical Methods | psychiatric | Post hoc analyses were performed on data collected during the first esketamine treatment session. Data were analyzed from the 40-minute measurement taken on the first day of dosing, as this provided the greatest range of CADSS total scores (Confirmatory factor analyses of these data were performed to determine the goodness-of-fit of recently published 1- and 3-factor solutions (As neither the 1-factor nor 3-factor solutions proved satisfactory (data reported in Results section), an exploratory factor analysis using principal axis factoring and direct oblimin rotation was conducted to identify the underlying structure of CADSS items. The oblique direct oblimin rotation, appropriate for correlated factors, was used due to the inherent correlation often observed between psychiatric symptoms (Frequency counts of the CADSS items and the BPRS+ total scores were stratified according to investigator-reported severity of dissociation (i.e., “not reported,” “mild,” “moderate,” or “severe”). Given the skewed nature of the data, with most patients having low scores on the BPRS+ and CADSS, a Spearman rank correlation was performed to determine the relationship between the measures.To investigate the relationship between CADSS scores and investigator-reported severity of dissociation, equipercentile linking following the method of | PMC10032296 | |
STUDY RESULTS | TRD, delusions, depressive disorder, Hallucinations, MDD, Depression | ADVERSE EVENTS, EVENTS, ADVERSE EVENT | A total of 764 patients with TRD were included in the post hoc analyses (Demographics and Clinical CharacteristicsAbbreviations: MADRS, Montgomery and Åsberg Depression Rating Scale; MDD, major depressive disorder; XR, extended release.On day 1, investigators reported an adverse event of dissociation for 14.3% (109/764) of the patients. Most of the dissociation events were characterized by the investigator as mild (n = 78), some were characterized as moderate (n = 26), and few (n = 5) were characterized as severe. Severe adverse events of dissociation were more often reported for female patients and patients who were younger, on average, than those for whom mild-to-moderate dissociation events were reported, though this pattern cannot be generalized due to the small number of patients in this subgroup. Dissociative symptoms generally resolved by 1.5 hours after esketamine dosing.Hallucinations, in contrast, were less frequent and delusions were not reported as adverse events for any patient. Hallucinations were reported in <1% of the sample (5/764). Using BPRS+ score ranges as criteria ( | PMC10032296 |
CADSS Cutoff for Determination of Dissociation | Clinician-Administered | EVENTS, ADVERSE EVENT | A CADSS total score >4 was determined to be the most useful in discriminating between those who were classified as experiencing dissociation per adverse event report and those who were not, per the Diagnostic Characteristics of CADSS When Used to Identify Investigator-Reported Dissociation Adverse EventsAbbreviations: CADSS, Clinician-Administered Dissociative States Scale.
Consistent with the results of the Youden Index, CADSS total scores generally followed the expected pattern, but with substantial variability (Distribution of CADSS total score by investigator-reported severity of dissociation. Abbreviations: CADSS, Clinician-Administered Dissociative States Scale; NR, adverse event of dissociation not reported. Note: The moderate and severe groups are combined due to the small number of patients rated as experiencing severe events. | PMC10032296 |
CADSS Factor Structure | According to CFA, neither the 3-factor solution reported by Principal axis factoring identified a 1-factor solution, with an eigenvalue of 8.5 and no other factor reaching 1.0. This single factor accounted for 86% of the variance, with 22 of the 23 items of the scale having loadings of at least 0.35. Given the single-factor solution, no rotation technique was required. | PMC10032296 | ||
CADSS Items Associated With Severity of Reported Dissociation Adverse Events | Clinician-Administered | ADVERSE EVENT |
CADSS Item Endorsements by Severity of Dissociation as an Adverse Event as Reported by InvestigatorsAbbreviations: CADSS, Clinician-Administered Dissociative States Scale.
| PMC10032296 |
Association Between Presence of Dissociation and Presence of Psychosis | hallucinations, delusions | ADVERSE EVENTS, ADVERSE EVENT | The aforementioned infrequency of delusions and hallucinations being reported as adverse events limited our ability to quantitatively examine these adverse event reports other than to note that dissociation typically occurred without these phenomena. On the psychometric measures, Spearman rank correlation revealed a weak but statistically significant positive relationship between the CADSS and BPRS+ (All 5 patients for whom hallucinations were reported had CADSS scores >4; however, 343 patients had CADSS scores >4 without reported hallucinations or delusions. Likewise, of the 113 patients for whom dissociation was reported as an adverse event, hallucinations were reported as an adverse event for only 3 (2.6%). | PMC10032296 |
DISCUSSION | TRD, treatment-resistant MDD, psychosis, psychotic disorders, behavioral and sensory experiences | ADVERSE EVENT | Dissociation is a pleomorphic clinical construct used to describe a relatively heterogenous set of behavioral and sensory experiences in different clinical contexts. In the treatment of TRD with glutamate receptor modulators, the aspects of dissociation most commonly described as associated with treatment are more limited; however, substantial variability remains between the cutoffs used on the CADSS and the aspects of dissociation most likely to be identified and/or evoke concern from clinicians.The results of our investigation of the characterization of dissociation in a group of patients with treatment-resistant MDD receiving their first treatment with esketamine nasal spray (in conjunction with recently started new oral antidepressant) echo this variability. We found that distinct dissociative experiences, as codified by the CADSS, did not cluster together but rather tended to move in the same direction in general as severity increased, consistent with the unifactorial nature of the CADSS items. Although the 4/5 threshold initially proposed by Some noteworthy differences exist between our study design and results compared with those reported by other groups investigating the factor structure of the CADSS among patients being treated with glutamatergic compounds. At the clinical level, both The modest correlation between investigator report and standardized assessment is not unique to this treatment setting (There was no single CADSS total score cutoff that could be viewed as a Item analysis across the range of reported adverse event severity suggests that there is no “universal” profile of dissociative symptoms associated with esketamine nasal spray. However, we found that, similar (but not identical) to the symptom clusters noted by In contrast, the relationship between dissociation and positive symptoms of psychosis is weak, unlike the pattern noted among clinical and nonclinical samples in a recent meta-analysis of studies that predominantly included participants suffering from psychotic disorders ( | PMC10032296 |
Limitations | psychotic symptoms, TRD, hallucinations, delusions | ADVERSE EVENT | As noted, these data are limited to those collected during the first (to our knowledge) open-label treatment session for patients being treated for TRD using esketamine nasal spray; consequently, doses were limited to 28 mg in patients ≥65 years and 56 mg for all others (In summary, although adverse event reports and CADSS scores generally move in the same direction, there is substantial variability in the dissociation-related experiences of patients taking esketamine, and there appears to be similar variability in the correlation between CADSS total scores and the identification of dissociation as an adverse event by observing clinicians. Even with this variability, however, it is clear that overt psychotic symptoms (delusions or hallucinations) are not a common aspect of the dissociative experiences associated with esketamine nasal spray administered in the dose range and frequency for which this agent is approved for use in TRD. | PMC10032296 |
Acknowledgments | We acknowledge Sandra Norris, PharmD, of the Norris Communications Group LLC for medical writing assistance and Ellen Baum, PhD (Janssen Global Services, LLC) for additional editorial support. Dr. Ibrahim Turkoz conducted the statistical analyses. All authors were involved in interpretation of the results and writing and/or revising the manuscript. All authors meet ICMJE criteria and all those who fulfilled those criteria are listed as authors.The open access fee was paid by Janssen Research & Development, LLC, Titusville, NJ, USA, which also provided funding for the work reported in this article. | PMC10032296 | ||
Data Sharing and Accessibility | Johnson & Johnson is | The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at | PMC10032296 | |
Interest Statement | Drs David Williamson, Ibrahim Turkoz, Stephane Borentain, Ewa Wajs, Jaskaran B. Singh, and Wayne C. Drevets were employees of Janssen Scientific Affairs, Janssen Research & Development, LLC, or Janssen Research & Development Belgium at the time this work was conducted and hold company equity. | PMC10032296 | ||
Role of the Sponsor | Employees of the sponsor, as noted in author contributions, were involved in data analysis or interpretation and/or other aspects pertinent to this work. Authors had full access to all of the data, were involved in writing and/or revising the manuscript, and had final responsibility for the decision to submit for publication. | PMC10032296 | ||
Previous Presentations | Elements of this research were presented in poster form at the 15th Annual Scientific Meeting of the International Society for CNS Clinical Trials and Methodology, February 19-21, 2019, Washington, DC. | PMC10032296 | ||
References | PMC10032296 | |||
Background | Lactic Acidosis, diabetic | LACTIC ACIDOSIS | Despite paucity of data, it is common practice to discontinue metformin before invasive coronary angiography due to an alleged risk of Metformin-Associated Lactic Acidosis (M-ALA). We aimed at assessing the safety of metformin continuation in diabetic patients undergoing coronary angiography in terms of significant increase in lactate levels. | PMC9902064 |
Methods | diabetic, associated-acute kidney injury | In this open-label, prospective, multicentre, single-arm trial, all diabetic patients undergoing coronary angiography with or without percutaneous coronary intervention at 3 European centers were screened for enrolment. The primary endpoint was the increase in lactate levels from preprocedural levels at 72-h after the procedure. Secondary endpoints included contrast associated-acute kidney injury (CA-AKI), M-ALA, and all-cause mortality. | PMC9902064 | |
Results | non-cardiac, diabetic | 142 diabetic patients on metformin therapy were included. Median preprocedural lactate level was 1.8 mmol/l [interquartile range (IQR) 1.3–2.3]. Lactate levels at 72 h after coronary angiography were 1.7 mmol/l (IQR 1.3–2.3), with no significant differences as compared to preprocedural levels (p = 0.91; median difference = 0; IQR − 0.5 to 0.4 mmol/l). One patient had 72-h levels ≥ 5 mmol/l (5.3 mmol/l), but no cases of M-ALA were reported. CA-AKI occurred in 9 patients (6.1%) and median serum creatinine and estimated glomerular filtration rate remained similar throughout the periprocedural period. At a median follow-up of 90 days (43–150), no patients required hemodialysis and 2 patients died due to non-cardiac causes. | PMC9902064 | |
Graphical Abstract | PMC9902064 | |||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12933-023-01744-4. | PMC9902064 | ||
Keywords | PMC9902064 | |||
Background | DIABETES MELLITUS (DM) | In the past decades, the prevalence of diabetes mellitus (DM) has significantly increased worldwide, and it is estimated that 592 million people will be affected by DM in 2035 [ | PMC9902064 | |
Research design and methods | PMC9902064 | |||
Study design and population | diabetic | This is an open-label, prospective, multicentre, single-arm trial. All diabetic patients undergoing coronary angiography with or without PCI at 3 participating centers (Additional file Coronary angiography and PCI were performed according to standard techniques; stent and technique choice were based on operators’ preferences and there were no related exclusions. A low-osmolar, non-ionic contrast medium (iomeprol) has been used during the entire study period. Per the standard clinical protocol, up to 1 ml/Kg/h of saline up to 12 h before and up to 24 h after PCI were strongly recommended, although not mandatory. The total amount and type of hydration infused were prospectively collected. Antithrombotic regimen was based on parenteral heparin, and the use of oral aspirin plus a P2YA dedicated data coordinating center performed all data management. All data were entered prospectively in the database.The study complies with the Declaration of Helsinki and each patient provided written informed consent before coronary angiography. The study was approved by the Institutional Review Board at each site before enrollment and is registered with ClinicalTrials.gov, number NCT04766008. | PMC9902064 | |
Endpoint definitions and follow-up | ACUTE KIDNEY INJURY | The primary endpoint was the difference in lactate levels from preprocedural levels at 72 h after coronary angiography. Secondary endpoints included CA-AKI, M-ALA, and all-cause mortality. CA-AKI was defined according to the Acute Kidney Injury Network criteria as an increase by ≥ 50% or ≥ 0.3 mg/dl within 72 h after coronary angiography compared to pre-coronary angiography serum creatinine [ | PMC9902064 | |
Statistical analysis | diabetic | The sample size was calculated to detect with 90% power a prespecified increase of lactate of 20% from preprocedural levels, with a "one-side" probability of alpha error of 0.025. Sample size calculation was based on data from our historical cohort of diabetic patients taking metformin scheduled for coronary angiography, presenting a mean value of lactate before coronary angiography of 1.2 ± 0.7 mmol/l. A total of 150 patients was planned to be enrolled assuming dropout and attrition rate of 20% and 5%, respectively.Continuous variables were reported as mean ± standard deviation or median and interquartile range (IQR) and compared with Student’s t test or Mann–Whitney or Wilcoxon tests on the basis of normality of data, verified by Shapiro–Wilk test. Categorical variables are reported as N (%) and were compared with χ | PMC9902064 | |
Results | PMC9902064 | |||
Outcomes | PMC9902064 | |||
Postprocedural lactate levels | Median preprocedural lactate level was 1.8 (1.3–2.3) mmol/l, with increased level reported in patients treated with higher dosage of metformin (ρ = 0.18, p = 0.027), while there was no correlation with eGFR (p = 0.984). Lactate levels measured at 72 h after coronary angiography were 1.7 (1.3–2.3) mmol/l, with no significant differences compared to preprocedural levels (p = 0.908), as the median difference between pre- and postprocedural levels was 0 (− 0.5 to 0.4) mmol/l (Fig. Cumulative curves reporting preprocedural and 72-h lactate levels and their difference. Cumulative curves depict the sum of the frequency of preprocedural, 72-h lactate levels and their difference for all patients | PMC9902064 | ||
Conclusions | DM, diabetic | Metformin is recommended as first line therapy in patients with type 2 DM and is one of the most common drugs assumed by patients scheduled for coronary angiography. The present study expands the limited evidence on the safety of metformin continuation in patients undergoing coronary angiography and PCI. The main findings of our study are as follows:In diabetic patients without high-risk features for metformin accumulation, metformin continuation before and after coronary angiography with or without PCI resulted in similar preprocedural and 72-h lactate levels.The risk of CA-AKI was low, and no patients required hemodialysis during the index hospitalization or at mid-term follow-up. | PMC9902064 | |
Glycemic control and adverse events in patients undergoing coronary angiography and PCI | Early guidelines recommendations on the discontinuation of metformin before coronary angiography were based on expert opinion, due to the paucity of evidence in this setting. A common recommendation was to hold metformin on the day of contrast media administration and for the following 48 h, irrespective of the risk of CA-AKI and metformin accumulation [ | PMC9902064 | ||
Risk of CA-AKI and M-ALA with metformin continuation before and after coronary angiography and PCI | diabetic patients [ | HYPERGLYCEMIA | Based on this evidence, the risk–benefit trade-off for metformin continuation or suspension should be weighted considering the risk of hyperglycemia, M-ALA, and CA-AKI. Metformin represents the first-line therapy for diabetic patients [ | PMC9902064 |
Current practice and inconsistency in guidelines | diabetic, chronic kidney disease, PCI.In | COMPLICATION | Current clinical practice guidelines only marginally take into account the evidence provided thus far, probably reflecting the fear of M-ALA and its related mortality and the limitations of the studies evaluating the risk of metformin continuation in patients undergoing coronary angiography and PCI. In addition, guidelines are inconsistent in several aspects, such as timing to stop and restart metformin and to check creatinine and eGFR before and after the procedure [Our study provides evidence-based support to the current European guidelines on myocardial revascularization, which recommend checking renal function in patients assuming metformin and withhold metformin if renal function deteriorates (class of recommendation I, level of evidence C). The findings from our prospective study shows that—in case of limited risk for metformin accumulation—metformin continuation does not lead to a significant increase of lactate levels at 72 h as compared to preprocedural levels and that creatinine assessment before and at 72 h after coronary angiography and PCI ensures the safety of metformin continuation. Moreover, we observed that metformin continuation is associated with adequate glycemic control and with a low risk for CA-AKI. Based on our findings, metformin should not be discontinued prior to coronary angiography and PCI. Creatinine assessment at 72 h after the procedure assures to identify all patients with CA-AKI and subsequent risk of metformin accumulation.The present study should be interpreted considering some limitations. First, despite the prospective collection of procedural, pharmacologic, and clinical features, our results can only be considered hypothesis-generating, and a randomized controlled trial is required for a definite confirmation. However, a randomized trial aiming at evaluating the risk of M-ALA as compared to placebo is unfeasible, considering the excessively large sample size needed. A randomized trial powered to detect differences in a surrogate marker of M-ALA, such the increase of lactate, could be the best option to definitely quantify the risk of this complication among patients assuming metformin and scheduled for coronary angiography and PCI. Second, based on the study exclusion criteria, our findings cannot be applied to high-risk patients, such as those with severely reduced ejection fraction or severe chronic kidney disease. However, most patients presenting one or more exclusion criteria are not eligible for metformin therapy, rendering our findings generalizable to the large majority of patients treated with metformin undergoing coronary angiography and PCI.In conclusion, metformin continuation prior to coronary angiography and PCI is not associated with increased levels of lactate or decline in renal function in diabetic patients without high-risk features for its accumulation, such as severely reduced ejection fraction or severe chronic kidney disease, suggesting that metformin suspension before coronary angiography and PCI is not necessary. | PMC9902064 |
Prior presentation | MAY | The present study has been presented at EuroPCR 2022, on 17 May 2022. | PMC9902064 | |
Author contributions | MC, JSS, GF and GGS conceived the idea and design for the study. MC and JJS analysed the data. All authors contributed to interpret the data. MC, JSS, and RP drafted the manuscript. All authors contributed to revise the draft critically for important intellectual content and approved the final manuscript. MC, JJS and GGS are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript. | PMC9902064 | ||
Funding | This work is supported by a research grant from the Italian Ministry of Education to Prof Giulio Stefanini (PRIN 2017N8K7S2). | PMC9902064 | ||
Availability of data and materials | Data are available on reasonable request. | PMC9902064 | ||
Declarations | PMC9902064 | |||
Ethics approval and consent to participate | The study complies with the Declaration of Helsinki and was approved by the Ethics Committee of Humanitas Clinical and Research Hospital. | PMC9902064 | ||
Consent for publication | Not required. | PMC9902064 | ||
Competing interests | Dr. Garcia-Garcia reports the following institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips, and Corflow. Dr. Mehran reports grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc, Roivant Sciences, Sanofi, Medtelligence (Janssen Scientific Affairs), Janssen Scientific Affairs; other from Abbott laboratories, other from Abiomed, other from Bristol Myers Squibb, other from Claret Medical, other from Elixir Medical, other from The Medicines eCompany, other from Spectranetics/Philips/Volcano Corp, other from Watermark Research Partners; non-financial support and other from Regeneron Pharmaceuticals, Idorsia Pharmaceuticals Ltd. Dr. Reimers has received speaker honoraria from Boston Scientific. Dr. Stefanini reports a research grant from Boston Scientific and speaker or consulting fees from B. Braun, Biosensors, and Boston Scientific. All other authors report no relationships relevant to the contents of this paper to disclose. | PMC9902064 | ||
Patient and public involvement | Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research. | PMC9902064 | ||
References | PMC9902064 | |||
Objective | Academic Editor: Yuli Huang To evaluate the safety and efficacy of adrenal venous sampling (AVS) via the cubital vein and femoral vein synchronously. | PMC10439828 | ||
Methods | primary aldosteronism | PRIMARY ALDOSTERONISM | A total of 200 patients with primary aldosteronism admitted to the First Hospital of Fujian Medical University were enrolled and randomly divided into a single-path AVS group (SP, | PMC10439828 |
Results | MP | There was no statistical difference between the two groups at baseline. Multipath AVS had a significantly higher success rate of right-sided intubation than single-path AVS (success rate of right-sided intubation/%: SP 87.96 vs MP 95.65, | PMC10439828 | |
Conclusion | PRS | Multipath AVS via the cubital vein and femoral vein improves the success rate of AVS with comparable safety compared to single-path AVS. When the RAV is opened in the III quadrant, the TIG catheter improves the cannulation success rate. The multipath AVS method provides more catheter options. Patients diagnosed with PA at the First Hospital of Fujian Medical University from December 2019 to December 2021 were included. The collection of medical records of the included population was approved by the ethics committee (approval number: [2021] 311). This was a cross-sectional study in which some patients were treated surgically and some were treated with superselective adrenal artery embolization (SAAE). We conducted a cohort study of patients treated with SAAE. ClinicalTrials.gov Protocol Registration and Results System (PRS) receipt release date: January 11, 2022. This trial is registered with | PMC10439828 | |
1. Introduction | fits, confusion, hypokalemia | CLINICAL SYNDROME, HYPERTENSION, PRIMARY ALDOSTERONISM | Primary aldosteronism (PA) is a clinical syndrome characterized by high aldosterone, low renin activity, hypertension, and hypokalemia [The high success rate of AVS has contributed to the development of unilateral adrenalectomy. Many studies have attempted to accomplish AVS through different vascular accesses, catheters, and devices.When performing AVS, the catheter is superselectively embedded into the bilateral adrenal veins to obtain blood, and even when blood is obtained near the adrenal veins, the blood specimen will still be diluted, affecting the accuracy. Commonly selected sites for blood sampling are the elbow vein and the femoral vein [Due to the different venous opening locations and imaging patterns, as well as the confusion of small branches of the surrounding hepatic veins, the success rate of the right adrenal gland is only about 80% [In the past, researchers tried to improve the success rate of AVS and avoid adrenal vein hemodilution. Some studies proposed effective methods [To address the misclassification from asynchronous AVS of the right and left adrenal glands, some centers use continuous ACTH stimulation; however, ACTH stimulation may reverse the results of the lateralized side [This study is a single-center prospective study that showed an increased success rate of right-sided cannulation to 95%. The study found that the choice of catheter depended on the axial position of the central RAV. For example, when the RAV opening was in quadrant I, an MPA catheter may be the most appropriate. When the RAV opening was in quadrant III, the MPA catheter became difficult to detect. Using a catheter that fits the direction of the adrenal vein opening improved the success rate of AVS. The multipath method expanded catheter selection.In addition, we used multipath AVS through the cubital vein and femoral vein to successfully complete simultaneous AVS. A comparison was made with single-path AVS to compare the effectiveness and safety of the new method. AVS is the gold standard for staging the diagnosis of PA, and we hope to obtain more information through the analysis. | PMC10439828 |
2. Methods | PMC10439828 | |||
Study Cohort ( | BLOOD | The trial was a national, prospective, single-arm experimental pilot study. Blood screening (aldosterone-to-renin ratio, ARR) was performed at the First Hospital of Fujian Medical University from December 2019 to December 2021, followed by a confirmatory test (dynamic tests to suppress aldosterone production by salt loading, volume expansion, or inhibition of angiotensin-converting enzyme) from December 2019 to December 2021 in the First Affiliated Hospital of Fujian Medical University. A total of 200 patients were diagnosed with PA according to the criteria of an Endocrine Society Clinical Practice Guideline [All patients underwent computed tomography (CT) and AVS and were randomized by a coin flip into two groups, including a single-path group and a multipath group. The single-path group used the cubital vein asynchronous AVS and the multipath group used synchronized AVS via the cubital vein and femoral vein.This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University. The registration number was [2015]084 of the First Affiliated Hospital of Fujian Medical University. | PMC10439828 | |
2.2. Inclusion Criteria | Hypertension | HYPERTENSION, ENDOCRINE HYPERTENSION | Patients with PA were established based on the standards and followed by the flowchart developed by the 2020 Working Group on Endocrine Hypertension of the European Society of Hypertension ( | PMC10439828 |
2.3. Exclusion Criteria | abnormal coagulation, allergy, hyperthyroidism, iodine allergy, End-stage of the malignant tumor, systemic infection, acute stroke | ACUTE MYOCARDIAL INFARCTION, ABNORMAL COAGULATION, ALLERGY, HYPERTHYROIDISM, IODINE ALLERGY, SYSTEMIC INFECTION, ACUTE STROKE | Patients who were with following conditions were excluded. (1) Patients with severe iodine allergy were at risk for contrast agent allergy. (2) Patients with abnormal coagulation must be corrected first. (3) Patients with acute stroke, acute myocardial infarction, and major surgical history within 1 month were excluded. (4) End-stage of the malignant tumor was excluded. (5) Patients with uncorrected hyperthyroidism were excluded for selected AVS. (6) There were no evidence-based medical studies to support pregnant women, lactation, and planned pregnancy patients undergo AVS. (7) Patients with severe systemic infection and being under mechanical ventilation were excluded. | PMC10439828 |
2.4. Patients Demographic Characteristics | thrombosis, death, fever, hematoma, ±2 | THROMBOSIS, INTRAOPERATIVE COMPLICATIONS, POSTOPERATIVE COMPLICATIONS, MINOR, VASCULAR RUPTURE, HEMATOMA | (1) Age, sex, height, weight, serum cholesterol, triglycerides, low-density lipoprotein cholesterol, creatinine, glomerular filtration rate, uric acid, and glycated hemoglobin were assessed at baseline. (2) Collected indicators reflecting PA characteristics, including systolic blood pressure (SBP), diastolic blood pressure (DBP), antihypertensive drugs, and biochemical indicators (plasma potassium, aldosterone, and renin).Plasma renin, aldosterone, and aldosterone-renin ratio levels were assessed at baseline by a clinical laboratory (ACM Global Laboratories, Rochester, NY, USA). Patients abstained from all antihypertensive medications and were requested to fast prior to testing. Patients must be out of bed for at least 2 hours after resting and quietly sitting for a minimum of 5 minutes but preferably 30 minutes before blood was sampled.The time and the patient's position (standing, sitting, or lying) at the time of blood collection were recorded. Later, the patient was asked to take the blood sample at the same time (±2 hours) and in the same position. (3) The primary efficacy of multipath AVS was evaluated by the success rate of unilateral intubation. Statistics of AVS intraoperative parameters were used to evaluate the minor efficacy of multipath AVS, including unilateral fluoroscopy time, total fluoroscopy time, contrast agent dosage, and operation cost. (4) The safety analysis between multipath AVS and single-path AVS included intraoperative complications (such as vascular dissection and vascular rupture) and postoperative complications (such as fever, hematoma, limb thrombosis, and death). | PMC10439828 |
2.5. AVS Procedure | adrenal venous blood sample | Single-path AVS was performed by a skilled operator. (1) After disinfection and anesthesia, the middle right cubital vein was punctured and a 5F sheath was inserted. (2) An X-ray was performed on the patient anterior chest and an F-type MPA catheter (Cordis, USA) was inserted into the inferior vena cava to collect a 2 ml adrenal vein blood sample. (3) A 5F MPA catheter was inserted into the RAV and a small amount of contrast medium was injected to determine the location. A 2 mL adrenal venous blood sample was taken (Multipath AVS was performed by two skilled operators simultaneously. (1) The right cubital vein and right femoral vein were punctured after disinfection and anesthesia, and 5F sheaths were inserted, respectively. (2) An X-ray was performed on the patient anterior chest and an F-type MPA catheter (Cordis, USA) was inserted into the inferior vena cava to collect a 2 ml adrenal vein blood sample. (3) Operators simultaneously delivered the 5F MPA catheter (Cordis, USA) into bilateral adrenal veins, and then injected a small amount of contrast agent to determine the location ( | PMC10439828 | |
2.6. AVS Parameter | Selectivity index (SI) was used to assess the adequacy of the adrenal vein cannulations and was calculated as Cortisol | PMC10439828 | ||
2.7. Statistical Analysis | SD | All data were collected, statistically analyzed, and tabulated using the SPSS 22 software (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as mean ± SD, such as age, height, weight, SBP, DBP, cholesterol, triglycerides, low-density lipoprotein cholesterol, serum creatinine, uric acid, and glycated hemoglobin. Aldosterone, renin, and ARR were expressed as medians with interquartile ranges. Categorical data variables were shown as number ( | PMC10439828 | |
3. Results | PMC10439828 | |||
3.1. Demographic Data ( | The SP-AVS group included 108 patients, 48 of whom were male, with a mean age of (51.07 ± 12.76) years. Baseline SBP was (157.15 ± 21.83) mmHg and baseline DBP was (92.16 ± 13.77) mmHg. In addition, 92 patients were included in the MP-AVS group with an age of (50.89 ± 12.77) years. Forty-five of them were male. Baseline SBP was (156.54 ± 21.54) mmHg and baseline DBP was (92.17 ± 12.81) mmHg. Serum potassium was (3.32 ± 0.56) mmol/L. There was no significant difference between the SP-AVS and MP-AVS groups in terms of baseline data. | PMC10439828 | ||
3.2. AVS Parameters and Complications Analysis | Compared with the SP-AVS, the success rate of right-side intubation in the MP-AVS was higher (success rate of right-side intubation/%: SP-AVS 87.96% vs MP-AVS 95.65%, | PMC10439828 | ||
3.3. Catheter Selection Analysis | In group I, MPA catheters were used in 163 cases (98.19%) and TIG catheters were used in 3 cases (1.81%). In group III, MPA catheters were used in 3 cases (17.65%) and TIG catheters were used in 14 cases (82.35%). As shown in | PMC10439828 | ||
4. Discussion | adrenal venous blood, hemodilution | PRIMARY ALDOSTERONISM, BENDING, POSTOPERATIVE COMPLICATIONS | In this study, we perceptively explored the safety and efficacy of single-path AVS and multipath AVS via the femoral vein and cubital vein for primary aldosteronism. The findings were as follows: (1) Multipath AVS via the cubital vein and femoral vein significantly improved the success rate of AVS and had comparable safety compared to single-path AVS. (2) The TIG catheter improved the success rate when the RAV was opened towards the III quadrant. (3) The multipath AVS approach expanded catheter options. The results showed that the multipath AVS technique (simultaneous adrenal vein sampling through the calf vein and femoral vein) allowed simultaneous collection of bilateral adrenal vein blood samples and shortened the X-ray exposure time. Moreover, this method expanded the catheter selection without increasing the cost of the procedure or postoperative complications.The multipath AVS technique was performed via the cubital vein and femoral vein synchronously. The modified multipath of AVS improved the success rate of AVS and enhanced the accuracy of diagnosis. AVS were initially performed using the SIMON catheter via the femoral vein single-path and later adopted single-path via the cubital vein by using a MPA catheter and a TIG catheter [The disadvantages of single-path AVS were fewer catheter options and the inability to perform simultaneous bilateral adrenal venous blood collection. To address the problem of fluctuating cortisol secretion during AVS, asynchronous AVS was used in the early days, followed by stimulation of AVS with ACTH [However, in many studies, the prognosis of patients with AVS-guided PA was not superior to that of patients with CT-guided prognosis. Huang [The AVS-guided prognostic analysis of PA is only of guiding value with accurate AVS results. While single-path AVS only allowed asynchronous extraction of adrenal blood, multipath AVS enabled synchronous blood extraction and allowed catheter selection based on the different opening positions of the adrenal veins in the planar quadrant. Only highly reliable AVS results were instructive for surgery. While single-path AVS only allowed asynchronous extraction of adrenal blood, multipath AVS enabled synchronous blood extraction and allowed catheter selection based on the different opening positions of the adrenal veins in the planar quadrant.The right-sided adrenal had a variable opening, and route and catheter diversification improved the success of cannulation. When the left-sided adrenal veins opening was deep or overlapped with the phrenic vein, diversification avoided imprecise cannulation and hemodilution caused by the single use of TIG catheters. Multipath AVS via the cubital vein and femoral vein significantly improved the success rate of AVS. ACTH stimulation was not required, which can reflect the results of lateral secretion. Also, incorrect typing diagnosis due to fluctuations in aldosterone and cortisol secretion in asynchronous AVS can be avoided.There were no reports on the use of TIG catheters in the AVS to access the RAV. We defined the axial location of the RAV opening and found a significant increase in the use of TIG catheters in the III quadrant. Multipath AVS expanded the options for alternative catheters, especially when MPA catheters cannot be inserted into the adrenal vein in conventional AVS. Due to the multipath AVS approach, alternative catheters such as TIG, SIMON, or VER 135° catheters can be used when the MPA catheter cannot be inserted into the adrenal vein.The TIG catheter improved the success of the operation because the TIG catheter had the advantage of bending upward proximally, and the second curvature of the catheter provided support when the TIG catheter was formed in the inferior vena cava. Therefore, we found that for patients with RAV opening in the III quadrant, the TIG catheter was more suitable for RAV implantation via the cubital vein.Our previous studies demonstrated the safety and feasibility of multipath AVS [We observed an interesting phenomenon. After the TIG entered the RAV via the cubital vein, we attempted a right anterior oblique 30° angiogram as the RAV almost overlapped the inferior vena cava on anterior-posterior fluoroscopy (In single-path AVS, the RAV is reached using an MPA catheter, and a TIG catheter was the only option for hooking the LAV opening. Sometimes only the first branch of the adrenal vein can be hooked through the cubital vein. For deeper openings in the left adrenal vein or openings overlapped with the phrenic vein, a microcatheter was required. The above were the reasons why single-path AVS was costlier. The variety of paths and catheters avoided imprecision of cannulation and hemodilution. Multipath access expanded the choice of catheters. The lower cost of the procedure and fewer postoperative complications demonstrated the superiority of multipath AVS. | PMC10439828 |
5. Conclusion | PRIMARY ALDOSTERONISM | This is the first study on the operational innovation of AVS that demonstrates the effectiveness and safety of simultaneous AVS treatment through the cubital vein and femoral vein, expanding the choice of catheters. The TIG catheter via the femoral vein is an option when the RAV is open towards the third quadrant.Single-center clinical studies, small samples, and existing selection bias are limitations of this study. This report is a preliminary study, and as the number of patients increases, we will conduct a multicenter, large-sample clinical study. In the future, we will include multiple catheters in the trial, such as the SIMON catheter and the VER135° catheter. We hope to increase the success rate of AVS to 100% and provide the gold standard of diagnosis for the treatment of primary aldosteronism. | PMC10439828 | |
Acknowledgments | Hypertensive, renal artery denervation, hypertensive | MYOCARDIAL FIBROSIS | The authors would like to acknowledge the other investigators, the staff, and the participants of the study for their valuable contributions. This study was supported by the grants as follows. (1) Startup Fund for scientific research, the Fujian Medical University: Effect of Xiongdan on myocardial fibrosis in spontaneously hypertensive rats by bile acid regulation. Grant number: 2021QH1105; (2) Startup Fund for scientific research, the Fujian Medical University: Hypertensive response sensitization mediates miR-128/RUBL2 signaling pathway and renal artery denervation intervention: 2022QH1082; (3) Hypertensive response sensitization (HTRS) was used to evaluate the reprogramming and mechanism of renal artery denervation (Rena) on central nervous system plasticity Grant number: 2022QNA041. | PMC10439828 |
Data Availability | The raw data supporting the conclusions of this article will be made available by the authors without undue reservation. | PMC10439828 | ||
Disclosure | Han Cai and Zhoufei Fang are co-first authors. | PMC10439828 | ||
Conflicts of Interest | The authors declare that there are no conflicts of interest. | PMC10439828 | ||
Authors' Contributions | primary aldosteronism, fever, hematoma, hypertension, inferior vena cava, hemodilution | PRIMARY ALDOSTERONISM, ALD, HEMATOMA, HYPERTENSION, COMPLICATIONS | Liangdi Xie MD, PhD, and Feng Peng MD, PhD, contributed to conception and design. Zhoufei Fang MD design the study, data reduction, follow-up, statistical analysis, and article writing. Zhoufei Fang is the major AVS operator. Han Cai MD contributed to data reduction and follow-up. Han Cai is also the major AVS operator. All AVS were completed by Zhoufei Fang and Han Cai in this study. Qixiang Zhang MD contributed to follow-up. Jin Gong MD, PhD, improved outpatient screening of hypertension patients. Wei Zhou contributed to native English expression. All authors have contributed to the article and approved the submitted version. Han Cai and Zhoufei Fang contributed equally to this work.Flow diagram for diagnosis and grouping of PA patients. Defined the intersection of RAV and IVC as the origin and established a plane coordinate system. In digital subtraction angiography (DSA) images, the RAV opening located on 0–3 o'clock direction was the first quartile (I) and 3–6 o'clock direction was the third quadrant (III) according to clock wise notation. (a) DSA image showed a MPA catheter embedded in the RAV opening, with the adrenal vein opening towards the I quadrant. (b) DSA image showed the central RAV entering the IVC in the III quadrant, which was defined as group III. A TIG catheter embedded in the RAV. (c) DSA image showed 5F MPA catheter embedded in the RAV opening and in the LAV opening, respectively, and synchronously. (d) The RAV could not be reached by repeated use of MPA and TIG catheter through single-path AVS via the cubital vein. A TIG catheter was used to reach the RAV, which was shown to open in the III quadrant on angiography. PA: primary aldosteronism; AVS: adrenal venous sampling; DRC: direct renin concentration; ARR: aldosterone-to-renin ratio; RAV: right adrenal vein; LAV: left adrenal vein; IVC: inferior vena cava.Techniques of using different catheters in single-path AVS and multipath AVS synchronously and asynchronously. (a) Inserted a 5F MPA catheter into the RAV in the single-path AVS group. (b) Inserted a 5F TIG catheter into the LAV in the single-path AVS group. Angiogram showed a thick common trunk vein formed by the confluence of the LAV and the PV. (c) To avoid local hemodilution of the LAV, a microcatheter was used to superselect into the LAV. Angiogram showed that the microcatheter superselected into the LAV. (d) 5F MPA catheter synchronously embedded in the RAV opening and in the LAV opening in the multipath AVS. (e) In anteroposterior position, intubated RAV through the cubital vein with a TIG catheter. (f) In right anterior oblique 30° angiography, the central venous opening of RAV was right oblique toward the III quadrant. (g) In anteroposterior position, intubated RAV with a MPA catheter via the femoral vein. (h) In right anterior oblique 30° angiography, the central venous opening of RAV was direct toward the III quadrant. Figures (e–h) show adrenal venography in the same patient in different positions. Figures (g, h) show that MPA catheter got through the femoral vein pathway and accurately positioned to the RAV with a total exposure time of 12.77 min. Figures (e, f) show that TIG catheter got through the cubital vein pathway, reaching the RAV with a total exposure time of 6.45 min. AVS: adrenal vein sampling; LAV: left adrenal vein; RAV: right adrenal vein; LRV: left renal vein; IVC: inferior vena cava; IEV: inferior emissary vein; PV: phrenic vein.Characteristics of baseline data between single-path group and multipath group with primary aldosteronism patients receiving AVS.SBP: systolic blood pressure; DBP: diastolic blood pressure; LDL: low-density lipoprotein cholesterol; ALD: serum aldosterone; DRC: serum renin concentration; ARR: aldosterone-to-renin ratio. Age was calculated in years from birthdate to date of informed consent.Parameters and complications of AVS.Success rate of right- or left-side intubation, vascular dissection, fever, and hematoma using correction Relationship of catheter selection and right adrenal vein opening axial position.
| PMC10439828 |
Background | The provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials. | PMC10646876 | ||
Objective | To involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK. | PMC10646876 | ||
Design | Research questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups. | PMC10646876 | ||
Participants | One hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds. | PMC10646876 | ||
Results | breast milk fortification, hypothermia | MILD HYPOXIC ISCHAEMIC ENCEPHALOPATHY, NECROTISING ENTEROCOLITIS | Two hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support. | PMC10646876 |
Conclusions | We have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care. | PMC10646876 | ||
WHAT IS ALREADY KNOWN ON THIS TOPIC | There is wide variability in neonatal care across the UK.Robust, high-quality interventional trials are the optimal approach to improving the evidence base and reducing variability in neonatal care.It is important to involve parents and other stakeholders in identifying important future research topics but this can be challenging and alternate approaches need to be developed. | PMC10646876 | ||
WHAT THIS STUDY ADDS | Previous prioritisation processes have identified broad themes of interest; this study identifies specific research questions suitable for answering in interventional trials. | PMC10646876 | ||
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY | This prioritised list of specific research questions can be used by research organisations to support and develop practice-changing interventional trials within neonatology. | PMC10646876 | ||
Introduction | Neonatal clinical care varies widely,Priority setting partnerships have been used throughout perinatal medicine and demonstrate the value of involving key stakeholders such as parents, patients and healthcare professionals alongside researchers.To reduce research waste, clinical uncertainties should be evaluated wherever possible through definitive randomised trials with sufficient power and methodological robustness to provide answers that inform clinical practice. | PMC10646876 | ||
Methods | A steering group guided the development and conduct of this work, including representatives from academia, key neonatal organisations, clinical neonatology, neonatal nursing, allied healthcare professionals (AHPs), statisticians and parents with experience of neonatal care (
| PMC10646876 | ||
Scope | The scope of the prioritisation process was developed and agreed by the steering group. Research questions had to be relevant to high-income neonatal care settings and proposed interventions expected to be delivered by neonatal teams. This included care provided on delivery suites, neonatal units, transitional care units and postnatal wards, during neonatal transport and within the community by neonatal teams after inpatient neonatal care. Research at pre-RCT stages of the translational pipeline was outside the scope of the process. | PMC10646876 | ||
Overview | Established research priority setting methodology as outlined by the James Lind Alliance was modified by the steering group to focus on detailed PICO questions, rather than general research themes or outcomes.Phase 1: identification of neonatal research questions suitable for addressing in RCTs.Phase 2: review of submitted neonatal research questions to remove duplicate questions and previously answered questions.Phase 3: prioritisation of neonatal research questions by all relevant stakeholders using a three-round eDelphi process.Phase 4: dissemination of ranked list of research questions in PICO format. | PMC10646876 |
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