Tag: nevin manimala

Trials. 2026 Apr 24. doi: 10.1186/s13063-026-09731-2. Online ahead of print.

ABSTRACT

BACKGROUND: Adenomyosis, an estrogen-dependent condition characterized by endometrial invasion into the myometrium, is associated with reduced live birth rates and increased miscarriage risk in women undergoing assisted reproductive technologies (ART). Gonadotropin-releasing hormone agonists (GnRH-a) are commonly used for pretreatment before frozen-thawed embryo transfer (FET) in adenomyosis patients, but optimal duration remains unclear. Letrozole, an aromatase inhibitor, may enhance GnRH-a efficacy by mitigating its flare-up effect and reducing peripheral estrogen production, yet high-level evidence on their combined effect is lacking. This study aims to compare the live birth rate and other pregnancy outcomes between one and two doses of GnRH-a pretreatment with or without letrozole supplementation in women with adenomyosis undergoing FET.

METHODS: This is a 2 × 2 factorial, multi-center, open-label, randomized controlled trial (RCT) conducted at three reproductive medical centers in China, with a planned enrollment of 432 women aged 20-38 years with sonographically diagnosed adenomyosis scheduled for single blastocyst FET. This study is designed as a superiority trial. Recruitment will be conducted by trained clinical research coordinators. Participants are randomized in a 1:1:1:1 ratio to four arms: one dose of GnRH-a (3.75 mg), two doses of GnRH-a, one dose of GnRH-a with letrozole (2.5 mg daily for 28 days), or two doses of GnRH-a with letrozole (2.5 mg daily for 28 days). The primary outcome is live birth rate. Secondary outcomes include fertility outcomes, pregnancy and obstetric outcomes, and neonatal outcomes. Safety outcomes, including the incidence and severity of low-estrogen-related adverse events (e.g., hot flashes, bone loss, vaginal dryness) and other serious adverse events, will be collected and compared. An internal pilot phase will assess procedural feasibility when approximately 25 participants are randomized per arm. Data are collected via medical records and follow-up assessments up to 6 months postpartum.

DISCUSSION: This factorial RCT is the first to assess the synergistic effects of GnRH-a dosage and letrozole supplementation, overcoming limitations of single-factor studies. By comprehensively evaluating pregnancy outcomes, the study aims to optimize pretreatment strategies, inform clinical guidelines, and improve pregnancy outcomes for adenomyosis patients undergoing FET.

TRIAL REGISTRATION: ClinicalTrials.gov NCT07065539. Registered on 14 July 2025. https://clinicaltrials.gov/study/NCT07065539. The first participant was enrolled in August 2025.

PMID:42032741 | DOI:10.1186/s13063-026-09731-2

J Cardiothorac Surg. 2026 Apr 24. doi: 10.1186/s13019-026-04235-1. Online ahead of print.

ABSTRACT

BACKGROUND: The increasing detection of pulmonary nodules through low-dose computed tomography screening has necessitated precise preoperative localization techniques. While local anesthesia is routinely used for CT-guided pulmonary nodule localization, it inadequately addresses deep tissue pain during pleural penetration. This study is to evaluate the analgesic efficacy and safety of ultrasound-guided erector spinae plane block (ESPB) during CT-guided pulmonary nodule localization.

METHODS: This single-center, prospective, randomized controlled trial was conducted from June 2024 to January 2025, enrolling 82 patients undergoing preoperative CT-guided pulmonary nodule localization. Participants were randomly assigned to either control group (local anesthesia with 4 ml 1% lidocaine) or ESPB group (ultrasound-guided ESPB with 20 ml 0.375% ropivacaine plus local anesthesia). The primary outcome was numerical rating scale (NRS) score during pleural penetration. Secondary outcomes included anxiety levels, radiation exposure, procedural time, hemodynamic parameters, pneumothorax incidence, and patient satisfaction. Statistical analysis was performed using independent-sample t-test and Mann-Whitney U test.

RESULTS: The ESPB group demonstrated significantly lower NRS scores during pleural penetration compared to the control group (2.68 ± 1.52 vs. 5.17 ± 1.32). Patients receiving ESPB exhibited reduced preoperative anxiety (44.71 ± 3.45 vs. 50.63 ± 3.74), decreased radiation exposure (401.06 ± 266.01 vs. 875.36 ± 377.45 mGy*cm), shorter fluoroscopy time (55.10 ± 10.54 vs. 117.39 ± 20.68 s, ), and lower pneumothorax incidence (4.88% vs. 19.51%), all P < 0.05. Post-procedural comfort scores and patient satisfaction were significantly higher in the ESPB group.

CONCLUSIONS: Ultrasound-guided ESPB improves analgesia, reduces anxiety, radiation exposure and complications while enhancing patient satisfaction during CT-guided pulmonary nodule localization, representing a valuable adjunct for thoracic interventional procedures.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06441071, registered May 8, 2024.

PMID:42032730 | DOI:10.1186/s13019-026-04235-1

Acta Neuropathol Commun. 2026 Apr 24;14(1):101. doi: 10.1186/s40478-026-02240-y.

NO ABSTRACT

PMID:42032706 | DOI:10.1186/s40478-026-02240-y

Environ Health. 2026 Apr 24. doi: 10.1186/s12940-026-01297-5. Online ahead of print.

NO ABSTRACT

PMID:42032672 | DOI:10.1186/s12940-026-01297-5

Arthritis Res Ther. 2026 Apr 24. doi: 10.1186/s13075-026-03815-9. Online ahead of print.

NO ABSTRACT

PMID:42032665 | DOI:10.1186/s13075-026-03815-9

BMC Med. 2026 Apr 24. doi: 10.1186/s12916-026-04831-x. Online ahead of print.

ABSTRACT

BACKGROUND: Transparency in randomized controlled trials (RCTs) has substantially improved in recent years, notably through trial registration and public availability of protocols and statistical analysis plans (SAPs). However, the reporting of protocol and SAPs modifications remains insufficiently standardized. As a result, even when these documents are publicly available, it is often challenging and time-consuming to identify what changes were made, why they were implemented, and whether they may affect the trustworthiness of the trial results.

ARGUMENTS: In this paper, we advocate for the development of a consensus-based framework for protocol modifications in RCTs. This need arises from the inherent tension between the necessity and the risks of protocol modifications. On the one hand, such modifications are often essential to address unforeseen operational, scientific, or ethical challenges. On the other hand, they may introduce bias and undermine confidence in trial findings, particularly when changes are data-driven or insufficiently justified. Although major transparency initiatives have strengthened trial reporting, important gaps persist. We review empirical evidence demonstrating the prevalence and nature of such modifications and discuss their potential implications for the validity, interpretation, and credibility of trial findings. Furthermore, readers, reviewers, and decision-makers face substantial challenges in identifying, understanding, and evaluating the potential impact of protocol changes. In the absence of standardized reporting, key information remains dispersed across multiple documents, placing an unreasonable burden on stakeholders to identify, interpret, and assess protocol modifications and their implications for the credibility of trial results.

CONCLUSIONS: Standardized and transparent reporting of protocol modifications is essential to ensure that their nature, timing, and rationale can be clearly understood and critically evaluated. We therefore advocate for the development of a consensus-based reporting framework, informed by a Delphi process, to improve transparency, facilitate critical appraisal, and strengthen confidence in RCT findings.

PMID:42032663 | DOI:10.1186/s12916-026-04831-x

Fluids Barriers CNS. 2026 Apr 24. doi: 10.1186/s12987-026-00803-8. Online ahead of print.

ABSTRACT

OBJECTIVE: Cerebrospinal fluid (CSF) over-drainage is an unintended sequela of using a shunt valve to treat hydrocephalus, and a second valve may be added in series to better control drainage. In this study, we tested whether the opening pressures of two valves in series-Codman Hakim ball valve (HBV) and the Miethke M.blue^Ⓡ adjustable gravitational valve (AGV)-can be treated as being additive using a novel in vitro benchtop model.

METHODS: Six dual-valve circuits were tested in triplicates for different combinations of HBV and AGV settings adding up to a summed opening pressure (OP) of either 20 or 40 cmH₂O. This “theoretical” sum was based on the addition of the nominal OP settings as stated by the manufacturer. Kruskal-Wallis tests and linear mixed-effect models were employed to analyze the flow rates for HBV-AGV settings with the same theoretical OP.

RESULTS: Kruskal-Wallis analysis demonstrated that HBV-AGV settings for each circuit, at a theoretical OP of 20 and 40 cmH₂O, showed statistically significant differences in flow rate. In linear mixed-effects models, as HBV OP was increased and composed a larger fraction of the theoretical OP, the flow rate decreased (effect size: -1.567 × 10^{– 3} mL/min/cmH₂O, standard error: 1.663 × 10^{– 4} mL/min/cmH₂O, p < 2 × 10^{– 16} at 20 cmH₂O, and effect size: -3.735 × 10^{– 3} mL/min/cmH₂O, standard error: 1.475 × 10^{– 4} mL/min/cmH₂O, p < 2 × 10^{– 16} at 40 cmH₂O, respectively).

CONCLUSION: An analysis of the flow data demonstrated statistically significant differences between combinations of HBV-AGV settings adding up to the same theoretical opening pressure. These findings suggest that in practice, the nominal OPs of Hakim and M.blue^Ⓡ valves may not be additive. Clinicians should be aware that drainage patterns can change when adjusting OPs of Hakim^Ⓡ and M.blue^Ⓡ valves under the assumption that HBV-AGV settings with the same summed theoretical OP behave alike.

PMID:42032645 | DOI:10.1186/s12987-026-00803-8

BMC Oral Health. 2026 Apr 24. doi: 10.1186/s12903-026-08355-x. Online ahead of print.

NO ABSTRACT

PMID:42032633 | DOI:10.1186/s12903-026-08355-x

J Cardiothorac Surg. 2026 Apr 24. doi: 10.1186/s13019-026-04170-1. Online ahead of print.

ABSTRACT

PURPOSE: Given the systemic nature of connective tissue diseases (CTD), open surgical intervention for aortic stenosis is often considered high risk, making transcatheter aortic valve replacement (TAVR) a potentially preferable alternative. However, data on the impact of CTD on TAVR outcomes remain limited. Therefore, we conducted a nationwide analysis using the National Inpatient Sample (NIS) to examine trends and in-hospital outcomes of TAVR in patients with CTD in the United States.

METHODS: A total of 90,298 patients undergoing TAVR between 2016 and 2022 were identified, representing over 451,000 weighted hospitalizations, including 3,821 (4.2%) with CTD. Multivariable regression was used to adjust for demographic, clinical, and hospital-level characteristics. CTD patients were more frequently female and had higher comorbidity indices, although many differences were small in absolute magnitude.

RESULTS: In-hospital mortality was comparable between CTD and non-CTD groups (1.0% vs. 1.2%, p = 0.345). Rates of permanent pacemaker implantation and major complications, including vascular events, were similar. CTD patients demonstrated modestly shorter length of stay and lower inflation-adjusted hospitalization costs. Lower rates of cardiogenic shock, cardiac arrest, and mechanical ventilation were observed in the CTD cohort. In-hospital mortality declined significantly over time in the overall cohort, with a similar directional trend in CTD patients that did not reach statistical significance, likely due to smaller sample size.

CONCLUSION: Overall, TAVR appears to be a safe and feasible therapeutic option in patients with CTD, with outcomes comparable to those without CTD.

PMID:42032618 | DOI:10.1186/s13019-026-04170-1

Trials. 2026 Apr 24. doi: 10.1186/s13063-026-09726-z. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: A Study Within A Trial (SWAT) is a research study embedded within a larger trial which aims to investigate different strategies for a particular trial process, such as trial recruitment. It is imperative such studies, which are often underpowered, employ efficient and informative analytical methods. The use of Bayesian methods and interpretation of SWAT results in this context requires exploration. Bayesian methods provide direct probability statements about intervention effects and readily enable ACceptability Curve Estimation using Probability above Threshold (ACCEPT) analyses, which consider the probability of the tested intervention being effective for different threshold values. Additionally, they provide an opportunity to incorporate the results of previous similar studies within the analysis using informative priors. This proof-of-concept study re-analysed two previous SWATs using Bayesian methods and ACCEPT analyses.

METHODS: A SWAT conducted by Du et al. in 2009 and a subsequent SWAT by Mattock et al. in 2020 compared a video intervention against standard patient information on trial recruitment. For each SWAT, a primary Bayesian analysis was performed using a logistic model with non-informative priors. Sensitivity analysis explored informative priors informed by meta-analysis of previous similar studies; this included an analysis of the Mattock et al. SWAT incorporating the result of the earlier Du et al. SWAT. ACCEPT curves were constructed. Results were compared with frequentist analyses.

RESULTS: For the Du et al. SWAT, the primary Bayesian analysis gave an OR for recruitment for the video relative to standard information of 2.12, 95% CrI: 0.38-4.65 and a posterior probability of the video being effective (OR > 1) of 0.86. When taking into account results of previous SWATs by using an informative prior there remained a moderately high probability of video benefit (0.82). For the latter Mattock et al. SWAT, the primary Bayesian analysis gave an OR for recruitment for the video relative to standard information of 0.26, 95% CrI: 0.07-0.51 and the posterior probability of the video being effective was 0.0005, indicating very little chance of effectiveness; ACCEPT plots facilitated interpretation by showing the probability that the video was better than standard information for OR > 0.8 was very small (0.0032). When taking into account the results of previous SWATs using an informative prior, including Du et al., the probability of the video being effective was still very small (0.12).

CONCLUSIONS: Bayesian methods and ACCEPT analyses offer solutions to challenges experienced in the analysis and interpretation of SWATs, which are often underpowered. Greater use of these analytical approaches within SWATs will lead to a more accessible, improved evidence base on how to effectively conduct trials.

PMID:42032615 | DOI:10.1186/s13063-026-09726-z