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Trials Jun 2024Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects,... (Comparative Study)
Comparative Study
Clinical trial results in context: comparison of baseline characteristics and outcomes of 38,510 RECOVERY trial participants versus a reference population of 346,271 people hospitalised with COVID-19 in England.
BACKGROUND
Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent.
METHODS
We compared baseline characteristics and mortality of RECOVERY participants recruited in England (n = 38,510) with a reference population hospitalised with COVID-19 in England (n = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality.
RESULTS
Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3-24.1%]; vs reference 24.8% [24.6-25.0%]), except during the first pandemic wave in the UK (March-May 2020) when adjusted mortality was lower in RECOVERY.
CONCLUSIONS
Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates.
TRIAL REGISTRATION
ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.
Topics: Humans; COVID-19; Male; England; Female; Middle Aged; Aged; Hospitalization; Aged, 80 and over; SARS-CoV-2; Comorbidity; Adult; Randomized Controlled Trials as Topic; Frailty
PubMed: 38951929
DOI: 10.1186/s13063-024-08273-9 -
Cardiovascular Diabetology Jul 2024The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine... (Meta-Analysis)
Meta-Analysis Review
The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI - 1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI - 1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.
Topics: Humans; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Adolescent; Child; Network Meta-Analysis; Female; Male; Treatment Outcome; Blood Glucose; Randomized Controlled Trials as Topic; Biomarkers; Bayes Theorem; Hypoglycemic Agents; Glycemic Control; Age Factors; Insulin; Dietary Supplements; Exercise Therapy; Exercise; Child, Preschool
PubMed: 38951907
DOI: 10.1186/s12933-024-02301-3 -
Journal of Cardiothoracic Surgery Jul 2024In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparative analysis of the analgesic effects of intercostal nerve block, ultrasound-guided paravertebral nerve block, and epidural block following single-port thoracoscopic lung surgery.
OBJECTIVE
In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery.
METHOD
A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects.
RESULTS
In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P < 0.05). However, there was a higher incidence of side effects observed in the EB group (P < 0.05).
CONCLUSION
The analgesic effect of PVB and EB following single-port thoracoscopic lung surgery is better than that of ICNB. PVB causes fewer side effects and complications and is safer and more effective.
Topics: Humans; Nerve Block; Female; Male; Middle Aged; Intercostal Nerves; Ultrasonography, Interventional; Pain, Postoperative; Thoracic Surgery, Video-Assisted; Aged; Pain Measurement; Adult; Thoracoscopy; Lung
PubMed: 38951892
DOI: 10.1186/s13019-024-02877-7 -
Journal of Orthopaedic Surgery and... Jun 2024It remains unclear whether the use of an orthopaedic traction table (TT) in direct anterior approach (DAA) total hip arthroplasty (THA) results in better outcomes. The... (Meta-Analysis)
Meta-Analysis Comparative Study
Indirect comparisons of traction table versus standard table in total hip arthroplasty through direct anterior approach: a systematic review and frequentist network meta-analysis.
BACKGROUND
It remains unclear whether the use of an orthopaedic traction table (TT) in direct anterior approach (DAA) total hip arthroplasty (THA) results in better outcomes. The aim of this systematic review and network meta-analysis was to compare the THA outcomes through DAA on a standard operating table and the THA outcomes through DAA on a TT.
METHODS
PubMed, Epistemonikos, and Google Scholar were searched for relevant randomized controlled trials (RCTs) up to 01 January 2024. An indirect comparison in network meta-analysis was performed to assess treatment effects between DAA on a TT and DAA on a standard table, using fixed-effects and random-effects models estimated with frequentist approach and consistency assumption. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated for continuous variables and odds ratios (ORs) with 95% CIs were estimated for binary variables.
RESULTS
The systematic review of the literature identified 43 RCTs with a total of 2,258 patients. DAA with TT had a 102.3 mL higher intraoperative blood loss and a 0.6 mmol/L lower Hb 3 days postoperatively compared with DAA without TT (SMD = 102.33, 95% CI 47.62 to 157.04; SMD = - 0.60, 95% CI - 1.19 to - 0.00). DAA with TT had a 0.15 lower periprosthetic fracture OR compared with DAA without TT (OR 0.15, 95% CI 0.03 to 0.86). There were no further significant differences in surgical, radiological, functional outcomes and in complication rates.
CONCLUSION
Based on our findings and taking into account the limitations, we recommend that particular attention be paid to the risk of periprosthetic fracture in DAA on a standard operating table and blood loss in DAA with TT. Since numerous other surgical, radiological, functional outcome parameters and other complication rates studied showed no significant difference between DAA on a standard operating table and DAA with TT, no recommendation for a change in surgical technique seems justified.
LEVEL OF EVIDENCE
Level I evidence, because this is a systematic review and meta-analysis of randomized controlled trials.
Topics: Humans; Arthroplasty, Replacement, Hip; Network Meta-Analysis; Traction; Treatment Outcome; Blood Loss, Surgical; Operating Tables; Randomized Controlled Trials as Topic; Postoperative Complications
PubMed: 38951886
DOI: 10.1186/s13018-024-04852-3 -
Journal of Experimental & Clinical... Jun 2024During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or...
BACKGROUND
During targeted treatment, HER2-positive breast cancers invariably lose HER2 DNA amplification. In contrast, and interestingly, HER2 proteins may be either lost or gained. To longitudinally and systematically appreciate complex/discordant changes in HER2 DNA/protein stoichiometry, HER2 DNA copy numbers and soluble blood proteins (aHER2/sHER2) were tested in parallel, non-invasively (by liquid biopsy), and in two-dimensions, hence HER2-2D.
METHODS
aHER2 and sHER2 were assessed by digital PCR and ELISA before and after standard-of-care treatment of advanced HER2-positive breast cancer patients (n=37) with the antibody-drug conjugate (ADC) Trastuzumab-emtansine (T-DM1).
RESULTS
As expected, aHER2 was invariably suppressed by T-DM1, but this loss was surprisingly mirrored by sHER2 gain, sometimes of considerable entity, in most (30/37; 81%) patients. This unorthodox split in HER2 oncogenic dosage was supported by reciprocal aHER2/sHER2 kinetics in two representative cases, and an immunohistochemistry-high status despite copy-number-neutrality in 4/5 available post-T-DM1 tumor re-biopsies from sHER2-gain patients. Moreover, sHER2 was preferentially released by dying breast cancer cell lines treated in vitro by T-DM1. Finally, sHER2 gain was associated with a longer PFS than sHER2 loss (mean PFS 282 vs 133 days, 95% CI [210-354] vs [56-209], log-rank test p=0.047), particularly when cases (n=11) developing circulating HER2-bypass alterations during T-DM1 treatment were excluded (mean PFS 349 vs 139 days, 95% CI [255-444] vs [45-232], log-rank test p=0.009).
CONCLUSIONS
HER2 gain is adaptively selected in tumor tissues and recapitulated in blood by sHER2 gain. Possibly, an increased oncogenic dosage is beneficial to the tumor during anti-HER2 treatment with naked antibodies, but favorable to the host during treatment with a strongly cytotoxic ADC such as T-DM1. In the latter case, HER2-gain tumors may be kept transiently in check until alternative oncogenic drivers, revealed by liquid biopsy, bypass HER2. Whichever the interpretation, HER2-2D might help to tailor/prioritize anti-HER2 treatments, particularly ADCs active on aHER2-low/sHER2-low tumors.
TRIAL REGISTRATION
NCT05735392 retrospectively registered on January 31, 2023 https://www.
CLINICALTRIALS
gov/search?term=NCT05735392.
Topics: Humans; Female; Breast Neoplasms; Receptor, ErbB-2; Liquid Biopsy; Middle Aged; Ado-Trastuzumab Emtansine; Aged; Trastuzumab; Adult; Biomarkers, Tumor
PubMed: 38951853
DOI: 10.1186/s13046-024-03105-9 -
Cardiovascular Diabetology Jun 2024Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose...
BACKGROUND
Glucokinase (GK) plays a key role in glucose metabolism. In the liver, GK is regulated by GK regulatory protein (GKRP) with nuclear sequestration at low plasma glucose level. Some GK activators (GKAs) disrupt GK-GKRP interaction which increases hepatic cytoplasmic GK level. Excess hepatic GK activity may exceed the capacity of glycogen synthesis with excess triglyceride formation. It remains uncertain whether hypertriglyceridemia associated with some GKAs in previous clinical trials was due to direct GK activation or impaired GK-GKRP interaction.
METHODS
Using publicly available genome-wide association study summary statistics, we selected independent genetic variants of GCKR and GCK associated with fasting plasma glucose (FPG) as instrumental variables, to mimic the effects of impaired GK-GKRP interaction and direct GK activation, respectively. We applied two-sample Mendelian Randomization (MR) framework to assess their causal associations with lipid-related traits, risks of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular diseases. We verified these findings in one-sample MR analysis using individual-level statistics from the Hong Kong Diabetes Register (HKDR).
RESULTS
Genetically-proxied impaired GK-GKRP interaction increased plasma triglycerides, low-density lipoprotein cholesterol and apolipoprotein B levels with increased odds ratio (OR) of 14.6 (95% CI 4.57-46.4) per 1 mmol/L lower FPG for MASLD and OR of 2.92 (95% CI 1.78-4.81) for coronary artery disease (CAD). Genetically-proxied GK activation was associated with decreased risk of CAD (OR 0.69, 95% CI 0.54-0.88) and not with dyslipidemia. One-sample MR validation in HKDR showed consistent results.
CONCLUSIONS
Impaired GK-GKRP interaction, rather than direct GK activation, may worsen lipid profiles and increase risks of MASLD and CAD. Development of future GKAs should avoid interfering with GK-GKRP interaction.
Topics: Mendelian Randomization Analysis; Humans; Genome-Wide Association Study; Adaptor Proteins, Signal Transducing; Risk Factors; Genetic Predisposition to Disease; Risk Assessment; Blood Glucose; Glucokinase; Biomarkers; Lipids; Phenotype; Carrier Proteins; Polymorphism, Single Nucleotide; Time Factors; Dyslipidemias; Fatty Liver
PubMed: 38951793
DOI: 10.1186/s12933-024-02321-z -
BMC Oral Health Jun 2024This study investigated the effectiveness of a deep convolutional neural network (CNN) in diagnosing and staging caries lesions in quantitative light-induced...
OBJECTIVES
This study investigated the effectiveness of a deep convolutional neural network (CNN) in diagnosing and staging caries lesions in quantitative light-induced fluorescence (QLF) images taken by a self-manufactured handheld device.
METHODS
A small toothbrush-like device consisting of a 400 nm UV light-emitting lamp with a 470 nm filter was manufactured for intraoral imaging. A total of 133 cases with 9,478 QLF images of teeth were included for caries lesion evaluation using a CNN model. The database was divided into development, validation, and testing cohorts at a 7:2:1 ratio. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) were calculated for model performance.
RESULTS
The overall caries prevalence was 19.59%. The CNN model achieved an AUC of 0.88, an accuracy of 0.88, a specificity of 0.94, and a sensitivity of 0.64 in the validation cohort. They achieved an overall accuracy of 0.92, a sensitivity of 0.95 and a specificity of 0.55 in the testing cohort. The model can distinguish different stages of caries well, with the best performance in detecting deep caries followed by intermediate and superficial lesions.
CONCLUSIONS
Caries lesions have typical characteristics in QLF images and can be detected by CNNs. A QLF-based device with CNNs can assist in caries screening in the clinic or at home.
TRIAL REGISTRATION
The clinical trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2300073487, Date: 12/07/2023).
Topics: Humans; Dental Caries; Neural Networks, Computer; Female; Quantitative Light-Induced Fluorescence; Male; Adult; Sensitivity and Specificity; Middle Aged; Adolescent; Young Adult; ROC Curve
PubMed: 38951770
DOI: 10.1186/s12903-024-04517-x -
BMC Pregnancy and Childbirth Jul 2024The rates of labor induction and cesarean delivery is rising worldwide. With the confluence of these trends, the labor induction rate in trials of labor after cesarean...
Short stature and vaginal dinoprostone as independent predictors of composite maternal-newborn adverse outcomes in induction of labor after one previous cesarean: a retrospective cohort study.
BACKGROUND
The rates of labor induction and cesarean delivery is rising worldwide. With the confluence of these trends, the labor induction rate in trials of labor after cesarean can be as high as 27-32.7%. Induction of labor after one previous cesarean (IOLAC) is a high-risk procedure mainly due to the higher risk of uterine rupture. Nevertheless, the American College of Obstetricians and Gynecologists considers IOLAC as an option in motivated and informed women in the appropriate care setting. We sought to identify predictors of a composite of maternal and newborn adverse outcomes following IOLAC.
METHODS
The electronic medical records of women who delivered between January 2018 to September 2022 in a Malaysian university hospital were screened to identify cases of IOLAC. A case is classified as a composite adverse outcome if at least one of these 11 adverse outcomes of delivery blood loss ≥ 1000 ml, uterine scar complications, cord prolapse or presentation, placenta abruption, maternal fever (≥ 38 C), chorioamnionitis, intensive care unit (ICU) admission, Apgar score < 7 at 5 min, umbilical artery cord artery blood pH < 7.1 or base excess ≤-12 mmol/l, and neonatal ICU admission was present. An unplanned cesarean delivery was not considered an adverse outcome as the practical management alternative for a clinically indicated IOLAC was a planned cesarean. Bivariate analysis of participants' characteristics was performed to identify predictors of their association with composite adverse outcome. Characteristics with crude p < 0.10 on bivariate analysis were incorporated into a multivariable binary logistic regression analysis model.
RESULTS
Electronic medical records of 19,064 women were screened. 819 IOLAC cases and 98 cases with composite adverse outcomes were identified. Maternal height, ethnicity, previous vaginal delivery, indication of previous cesarean, indication for IOLAC, and method of IOLAC had p < 0.10 on bivariate analysis and were incorporated into a multivariable binary logistic regression analysis. After adjustment, only maternal height and IOLAC by vaginal dinoprostone compared to Foley balloon remained significant at p < 0.05. Post hoc adjusted analysis that included all unplanned cesarean as an added qualifier for composite adverse outcome showed higher body mass index, short stature (< 157 cm), not of Chinese ethnicity, no prior vaginal delivery, prior cesarean indicated by labor dystocia, and less favorable Bishop score (< 6) were independent predictors of the expanded composite adverse outcome.
CONCLUSION
Shorter women and IOLAC by vaginal dinoprostone compared to Foley balloon were independently predictive of composite of adverse outcome.
Topics: Humans; Female; Pregnancy; Labor, Induced; Retrospective Studies; Adult; Dinoprostone; Vaginal Birth after Cesarean; Infant, Newborn; Oxytocics; Administration, Intravaginal; Pregnancy Outcome; Cesarean Section; Malaysia; Risk Factors
PubMed: 38951754
DOI: 10.1186/s12884-024-06650-5 -
Scientific Reports Jul 2024Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented...
Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.
Topics: Humans; Alzheimer Disease; Clinical Trials as Topic; Cognitive Dysfunction; Dementia; Eligibility Determination; Ethnicity; National Institute on Aging (U.S.); Patient Selection; United States; Black or African American; Hispanic or Latino; American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander
PubMed: 38951633
DOI: 10.1038/s41598-024-65767-x -
Neurocritical Care Jul 2024The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from...
BACKGROUND
The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative.
METHODS
The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented.
RESULTS
The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO) was lower than the pre-mAT PaO, whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO. In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg.
CONCLUSIONS
The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803.
PubMed: 38951444
DOI: 10.1007/s12028-024-02035-w