Nevin Manimala

Trials. 2025 Jun 18;26(1):211. doi: 10.1186/s13063-025-08931-6.

ABSTRACT

BACKGROUND: Participant Information Leaflets (PILs) are lengthy and increasingly complex, and could deter research participation. A shortened PIL may be more appealing as it is likely to provide a more a manageable volume of information. Previous research has found that shortened PILs are no less effective for recruitment outcomes, and we deemed it useful to replicate this in an online setting. We also decided to compare retention rates, given the potential for more information to increase participants’ motivation.

AIM: To evaluate the efficacy of a shortened vs standard-length PIL on trial recruitment and retention rates.

METHODS: This two-arm study within a trial (SWAT) was embedded in a host randomised controlled trial (RCT)-IBD-BOOST. Potential participants were randomised to receive a standard-length or shortened PIL electronically for recruitment to the host RCT. An ethics committee approved potential participants being blinded to this randomisation.

PRIMARY OUTCOME: The percentage of SWAT participants receiving the shortened vs standard PIL who were recruited to the RCT.

RESULTS: Four thousand two hundred one participants were randomised to the standard-length (n = 2099) and shortened (n = 2102) PIL arms. Thirty-four email queries were received about the PILs-18 from those who received the standard and 16 from those receiving the shortened. Seven hundred eight SWAT participants were recruited to the RCT-333 (15.86%) who received the standard-length PIL and 375 (17.84%) who received the shortened (OR = 1.15, (95%CI = 0.98, 1.35), p = 0.09). Retention rates in the RCT were not statistically different between groups.

CONCLUSION: We did not find evidence of a significant difference between RCT recruitment and retention rates in participants randomised to the standard-length PIL compared with the shortened. It may be that a shortened PIL has the same effect on recruitment and retention outcomes, providing that the trial does not require extensive information for other reasons (e.g. safety). Therefore, it could be argued that researchers have a choice about how long to make PILs, perhaps with a link to more detail. Alternatively, given that there was no benefit of the shortened PIL, it may be worth comparing written PILs with other methods of conveying information to determine optimal means of encouraging participation and retention in decentralised trials.

HOST TRIAL REGISTRATION: A randomised controlled trial of supported, online, self-management for symptoms of fatigue, pain and urgency/incontinence in people with inflammatory bowel disease: the IBD-BOOST trial (ISRCTN71618461 on ISRCTN registry).

PMID:40528252 | DOI:10.1186/s13063-025-08931-6

J Exp Clin Cancer Res. 2025 Jun 18;44(1):176. doi: 10.1186/s13046-025-03435-2.

ABSTRACT

Diffuse-type gastric cancer (DGC) accounts for approximately one-third of gastric cancer cases, but it is clinically more aggressive and associated with poorer survival prognosis compared to intestinal-type gastric cancer (IGC). Our study revealed significantly reduced ESRP1 expression in DGC patients relative to IGC counterparts, with its high expression positively correlating with DGC patient prognosis. Both in vitro and in vivo experimental models demonstrated that ESRP1 has the ability to hinder the malignant progression of DGC. Mechanistically, ESRP1 interacts with DHCR7, a ferroptosis-promoting regulator, thereby upregulating DHCR7 expression and enhancing ferroptosis susceptibility in DGC cells. In DGC patients with high ESRP1 expression, ferroptosis-inducing therapy emerges as a promising treatment alternative. Moreover, for ESRP1-low DGC cases, we identified several potent small-molecule drugs. These findings collectively position ESRP1 as a potential therapeutic target for DGC intervention.

PMID:40528239 | DOI:10.1186/s13046-025-03435-2

Scand J Trauma Resusc Emerg Med. 2025 Jun 17;33(1):106. doi: 10.1186/s13049-025-01423-1.

ABSTRACT

BACKGROUND: Resuscitative thoracotomy (RT) is a critical intervention for patients in traumatic cardiac arrest or hemorrhagic shock, where survival is highly dependent on the time required to perform the procedure. Despite its urgency, RT is still conducted using traditional thoracic retractors originally designed for scheduled surgeries, which pose challenges in emergency settings. To address these limitations, we developed a novel thoracic retractor optimized for RT and evaluated its performance compared to a conventional model.

METHODS: The novel retractor was designed with an arrow-shaped hook for improved intercostal insertion and a continuously rotatable handle to enhance procedural efficiency. A comparative study using excised porcine thoraxes was conducted to assess its performance. Six cm incisions were made in the intercostal spaces bilaterally before retractor insertion. Evaluators inserted the device, performed three handle rotations, and repeated the procedure using the other retractor on the contralateral side. The primary outcome was the time required for three rotations, while secondary outcomes included ease of insertion, ease of rotation, and hook stability, rated on a 6-point scale by evaluators.

RESULTS: Ten surgeons (n = 10) performed thoracotomy using both the novel and conventional retractors. Comparison of the time required for three handle rotations between the novel and conventional retractors demonstrated a statistically significant reduction with the novel retractor. The median time to complete three rotations was 16.0 [11.7-19.1] seconds with the novel retractor, compared to 7.0 [5.3-8.5] seconds with the conventional model (P < 0.01). The ease of insertion was rated significantly higher with the novel retractor compared to the conventional model (6.0 [5.5-6.0] vs. 2.5 [2.0-3.0], P < 0.01). The ease of rotation was also rated significantly higher with the novel retractor than with the conventional model (5.5 [5.0-6.0] vs. 2.5 [1.0-3.5], P < 0.01). In the evaluation of the hook stability, no significant difference was observed between the novel and conventional retractors (P = 1.0).

CONCLUSIONS: The novel thoracic retractor enables faster and easier thoracotomy compared to conventional model. Given the strong association between time and RT prognosis, this device is well-suited for RT procedures requiring rapid execution.

PMID:40528231 | DOI:10.1186/s13049-025-01423-1

Crit Care. 2025 Jun 17;29(1):246. doi: 10.1186/s13054-025-05494-5.

ABSTRACT

BACKGROUND: Selective Digestive Decontamination (SDD) prevents infections and reduces mortality in the intensive care unit (ICU). Microbiological surveillance is considered essential for effective decontamination and detecting antibiotic resistance. However, its optimal frequency is unclear. We compared microbiological yield and costs of different surveillance intervals during SDD.

METHODS: In a computational simulation study, using data from a Dutch ICU, three surveillance scenarios were compared: (A) twice-weekly, (B) once-weekly, and (C) no surveillance. The primary outcome was the number of clinically relevant potentially pathogenic microorganisms (PPMs) detected per scenario. Secondary outcomes included detection of colonisation persistence prompting SDD intensification and surveillance costs.

RESULTS: We included 8,499 ICU admissions, 52,553 clinical and 75,567 SDD cultures. Scenario A yielded 911 (95% CI 905-917) PPMs per 1,000 days, of which 90 (88-94) were clinically relevant: 9 (9-10) multidrug-resistant microorganisms, 68 (66-71) microorganisms resistant to standard therapy, and 13 (12-14) infection-related microorganisms. Scenarios B and C yielded 85 (82-88) and 77 (75-80) relevant PPMs, respectively (94% and 86% compared to scenario A). Scenario A identified 56 (55-58) cases of colonisation persistence per 1,000 days while scenarios B and C detected 43 (42-45) and 12 (11-12), respectively. Total costs of SDD surveillance were €78,774, €55,208, and €31,522 per 1,000 days for scenarios A, B and C.

CONCLUSION: Compared to twice-weekly surveillance, once-weekly microbiological surveillance reduces costs by 30% with 6% loss in clinically relevant PPM detections. No surveillance reduces costs by 60% with 14% detection loss.

PMID:40528229 | DOI:10.1186/s13054-025-05494-5

J Orthop Surg Res. 2025 Jun 17;20(1):597. doi: 10.1186/s13018-025-05935-5.

ABSTRACT

BACKGROUND: The incidence of anterior cruciate ligament (ACL) reconstructions among adolescents, particularly those involved in high-risk sports, has increased. Despite surgical advancements, outcomes remain worse than in adults. This study aimed to assess ACL reconstruction outcomes in patients under 16 years and compared to older patients. The prevalence of high pivoting sports in those undergoing revision or contralateral ACL reconstruction was also analyzed. We hypothesized that younger athletes experience poorer outcomes and higher rates of secondary surgeries.

METHODS: This study evaluated ACL reconstruction outcomes in patients under 16 years (Group 1) and compared them with those over 16 years (Group 2). A retrospective analysis was conducted on patients who underwent primary arthroscopic ACL reconstruction between 2007 and 2022. Ipsilateral and contralateral surgeries were analyzed in both groups. Patient-reported outcomes (Lysholm score, Knee Injury and Osteoarthritis Outcome Score [KOOS], Tegner Activity Scale, and International Knee Documentation Committee [IKDC] scores) were compared between the two groups. The impact of sports activity level and sex on revision rates was examined. Statistical tests, including two-sample Z tests and two-sample t-tests, were used for analysis. Secondary surgeries were defined as additional procedures after ACL reconstruction, microfracture, hardware removal, and arthrolysis.

RESULTS: Group 1 (average age: 15.2 years) included 70 patients with a follow-up of 6.9 years, and Group 2 (average age: 30.8 years) included 87 patients with a follow-up of 3.66 years. A significant age difference was found (p<0.001). Group 1 had higher rates of contralateral ACL surgeries (18.3% vs. 1.1%, p=0.03), meniscus surgeries (26% vs. 4.6%, p=0.003), and secondary surgeries (44% vs. 21%, p=0.01) compared to Group 2. Female athletes under 16 years had a significantly higher rate of contralateral ACL reconstruction (92% vs. 69%, p=0.020). In Group 1, the KOOS Pain score was significantly higher (95.6 vs. 94.0, p=0.033), but the Symptoms score was significantly lower (75.6 vs. 85.0, p<0.005).

CONCLUSION: Patients under 16 years undergoing ACL reconstruction had higher rates of both contralateral and ipsilateral ACL surgeries, as well as secondary surgeries, compared to older patients. Female adolescents had a significantly higher incidence of contralateral ACL reconstruction.

PMID:40528219 | DOI:10.1186/s13018-025-05935-5

Ital J Pediatr. 2025 Jun 17;51(1):192. doi: 10.1186/s13052-025-01977-x.

ABSTRACT

BACKGROUND: The shortage of Pediatric Intensive Care Unit (PICU) beds among some Italian regions is a major concern, especially during epidemics. During respiratory syncytial virus (RSV) bronchiolitis peak, Neonatal Intensive Care Units (NICU) often admit infants and toddlers requiring advanced respiratory support. We conducted a survey to quantify children hospitalized for RSV bronchiolitis in NICU in 2021 and to examine the adherence to treatment guidelines.

METHODS: Early Childhood Intensive Care Working Group of the Italian Society of Neonatology (SIN) conducted a survey distributed to SIN Network NICUs. The modified Delphi method was used to prepare the survey; duplicate responses were excluded. Analysis evaluated percentages.

RESULTS: Response rate was 67% (78/117 NICUs). Geographic distribution of responding centers was: 51% Southern-Islands, 38% North, 11% Center; 50% were Territorial Hospitals, 20% University Hospitals. Of respondents, 55% have 5-10 NICU beds; 70% routinely admit children > 44 weeks postconceptional age and > 28 days old, with a rate of < 10 toddlers/year in 50% of cases, 10-20 toddlers/year in 25% of cases and > 20 toddlers/year in 15%. In 2021, 40% of NICUs admitted < 10 bronchiolitis cases, 29% 11-20 cases. RSV was the leading cause of bronchiolitis. Reasons for NICU admission were respiratory distress syndrome (92%), feeding difficulties (58%), comorbidities (20%). High-flow oxygen (87%) and non-invasive ventilation (60%) were common respiratory supports provided; 10% of patients needed invasive ventilation. Treatment included inhaled steroids (46%), bronchodilators/systemic steroids (32%), antibiotics (40%); 60% of centers did not use sedation during NIV; 30% used midazolam, 13% dexmedetomidine, < 10% fentanyl.

CONCLUSIONS: Our survey highlights that during the RSV epidemic, NICUs admitted toddlers to receive advanced respiratory support unavailable in pediatric ICUs. Most of the NICUs admitted fewer than 10 toddlers per year and less than 10 bronchiolitis, posing skill challenges for medical staff. This supports SIN’s proposal to identify some “extended NICUs” in regions with limited PICU beds, to centralize toddlers after an adequate training to gain knowledge/technical skills specific of pediatric critical care. This would help to overcome the PICU beds storage. Adherence to bronchiolitis management guidelines resulted suboptimal, with frequent but unrecommended use of inhaled steroids, bronchodilators, and antibiotics.

PMID:40528201 | DOI:10.1186/s13052-025-01977-x

Crit Care. 2025 Jun 17;29(1):248. doi: 10.1186/s13054-025-05462-z.

ABSTRACT

Survivors of intensive care unit (ICU) are increasingly numerous because of better hospital care. However, several consequences of an ICU stay, known as post-intensive care syndrome, worsen long-term prognoses. A predominant feature in survivors is reduced muscle strength, mass, and physical function. This leads to lower exercise capacity, long-lasting physical disability, higher mortality risk, and subsequent health costs. While ICU-acquired muscle weakness has been extensively studied these past decades, underlying mechanisms of post-ICU muscle weakness remain poorly understood, and there is still no evidence-based treatment for improving long-term physical outcomes. One hypothesis, among others, could be that the pathophysiology is dynamic over time, differing between the acute ICU and post-ICU recovery periods. This narrative review aims to address the clinical, physiological and biological determinants of persistent muscle dysfunction in ICU survivors, with particular attention to the molecular, cellular and systemic mechanisms involved. Specifically, pre-ICU health factors such as obesity and sarcopenia, ICU-related complications and treatments, and post-ICU management all influence recovery. Dysfunctions in the neuroendocrine, vascular, neurological, and muscle systems contribute as physiological determinants of the muscle weakness. Complex and multifaceted biological mechanisms drive the post-ICU muscle dysfunction with mitochondrial and autophagy dysfunction, epigenetic modifications, cellular senescence, muscle inflammation with altered cell-cell communication, including dysfunction of immune cells, stem cell exhaustion and extracellular matrix remodelling. The review also sheds light on new and innovative therapeutic approaches and discusses future research directions. Emphasis is placed on the potential for multi-approach treatments that integrate nutritional, physical, and biological interventions. Addressing these aspects in a holistic and dynamic manner, from ICU to post-ICU phases, may provide avenues for mitigating the long-term burden of muscle weakness and physical disability in ICU survivors.

PMID:40528196 | DOI:10.1186/s13054-025-05462-z

Int J Equity Health. 2025 Jun 17;24(1):178. doi: 10.1186/s12939-025-02470-x.

ABSTRACT

BACKGROUND: Despite progress in maternal health coverage in Mexico, inequities persist, particularly in postnatal care. The COVID-19 pandemic further widened these gaps, disproportionately affecting women with similar health needs but different socioeconomic conditions. This study assesses trends in maternal healthcare coverage and inequity across nine stages of antenatal, delivery, and postnatal care, comparing pre- and post-pandemic periods. By examining horizontal inequity, we identify critical gaps and policy implications to enhance equitable maternal healthcare access.

METHODS: We conducted a population-based, pooled cross-sectional and retrospective analysis for the last three decades, using data from the five waves (1997, 2009, 2014, 2018, and 2023) of the Mexican National Survey of Demographic Dynamics (ENADID). Our study included 123,197 Mexican women aged 12-54 with recent live births, representing a population of 38.5 million. We estimated coverage for antenatal and postnatal care stages. We used multiple regression models to assess factors influencing the likelihood of receiving comprehensive antenatal care, skilled delivery care and postpartum care interventions, both pre-and post-COVID-19. We estimated horizontal inequity using concentration index and decomposition analysis to highlight disparities among women with similar needs and examine how these disparities have changed due to COVID-19 across nine antenatal, delivery, and postnatal care stages.

FINDINGS: Full antenatal and postnatal health care in Mexico was inadequate and inequitable. Only 73% of pregnant women received timely antenatal care and 88.3% received frequent care, despite 97.9% claiming to have received some care. Inadequate care was linked to lower education, labour market participation, low socioeconomic status, higher parity, and rural residency. The most inequitable aspects are access to skilled and institutional health care and timely post-partum care. The dismantling of a public health insurance system and focused strategies that incentivized the use of maternal health services during the pre-COVID period (January 2019 to March 2020) led to significant health coverage losses, exacerbating horizontal inequity in these areas. Although high equity was achieved in comprehensive antenatal healthcare from 2009 to 2023, since COVID, inequity has increased, particularly in antenatal indicators such as receiving four or more antenatal check-ups and check-ups in the first trimester. The pandemic intensified these inequities, and the values of these indicators have not returned to pre-pandemic levels, underscoring the seriousness of the situation.

CONCLUSIONS: Despite efforts to improve maternal care, comprehensive antenatal services reach only 61.8% of women in Mexico. This stresses not only the need for targeted policies to enhance antenatal, delivery, and postnatal coverage at critical stages of care, but also the need to continue strengthening strategies that have rendered good results, and not to eliminate them simply for political-ideological reasons. It is imperative to prioritize reducing existing inequalities within the population, as horizontal inequity reveals significant barriers preventing equitable access to maternal health services among women with similar needs. The most pronounced disparities exist in timely healthcare access, skilled deliveries, and institutional postnatal care, where systemic issues and financial constraints are particularly impactful. Addressing these inequities is essential not only to improve overall maternal health outcomes but also to ensure that all women can benefit from the full spectrum of maternal care, particularly in situations of health crisis, such as pandemics.

PMID:40528188 | DOI:10.1186/s12939-025-02470-x

Med Decis Making. 2025 Jun 17:272989X251342459. doi: 10.1177/0272989X251342459. Online ahead of print.

ABSTRACT

BackgroundEconomic evaluations for life-extending treatments frequently require clinical trial data to be extrapolated beyond the trial duration to estimate changes in life expectancy. Conventional survival models often display hazard profiles that do not rise as expected in an aging population and require the incorporation of external data to ensure plausibility. Relative survival (RS) models can enable the incorporation of external data at model fitting. A comparison was performed between RS and “standard” all-cause survival (ACS) in modeling outcomes from the tafamidis for the treatment of transthyretin amyloid cardiomyopathy (ATTR-ACT) trial.MethodsPatient-level data from the 30-mo ATTR-ACT trial were used to develop survival models based on parametric ACS and RS models. The latter was composed of an expected hazard and an independent excess hazard. Models were selected according to statistical goodness of fit and clinical plausibility, with extrapolation up to 72 mo validated against ATTR-ACT long-term extension (LTE) data.ResultsInformation criteria were too similar to discriminate between RS or ACS models. Several ACS models were affected by capping with general population mortality rates and considered implausible. Selected RS models matched the empirical hazard function, could not fall below general population hazards, and predicted well compared with the LTE data. The preferred RS model predicted the restricted mean survival (RMST) to 72 mo of 51.0 mo (95% confidence interval [CI]: 46.1, 55.3); this compared favorably to the LTE RMST of 50.9 mo (95% CI: 47.7, 53.9).DiscussionRS models can improve the accuracy for modeling populations with high background mortality rates (e.g., the ATTR-CM trial). RS modeling enforces a plausible long-term hazard profile, enables flexibility in medium-term hazard profiles, and increases the robustness of medical decision making.HighlightsTo inform survival extrapolations for health technology assessment, a relative survival model incorporating external data per the recommendations of the National Institute for Health and Care Excellence (NICE) Decision Support Unit was used in support of the NICE evaluation of tafamidis for treatment of transthyretin amyloid cardiomyopathy (ATTR-CM).Relative survival modeling allowed selection of a broader range of hazard profiles compared with all-cause survival modeling by ensuring plausible long-term predictions.Predictions from plausible relative survival models of overall survival in patients with ATTR-CM, extrapolated from the ATTR-ACT trial, validated very well to outcomes after a doubling of follow-up and demonstrated improved precision and accuracy versus parametric all-cause survival models.

PMID:40528187 | DOI:10.1177/0272989X251342459

BMC Nurs. 2025 Jun 17;24(1):654. doi: 10.1186/s12912-025-03257-9.

ABSTRACT

INTRODUCTION: Prematurity is a significant global health challenge. Premature infants frequently need invasive mechanical ventilation until their lungs are fully developed. Due to the possible complications of ventilation, nurses in the neonatal intensive care unit (NICU) must deliver specialized care to achieve the best outcomes for these infants.

OBJECTIVE: This study aimed to explore the effectiveness of nurses’ training in mechanical ventilation weaning on neonatal outcomes.

METHOD: A quasi-experimental non-equivalent group design was used with purposive sampling of 70 nurses and 64 newborn infants on invasive mechanical ventilation. The infants were divided into two groups: 32 weaned by trained nurses (study group) and 32 weaned by standard methods (control group). Data was collected using a structured questionnaire about the nurses and neonates. A well-designed training program, including theoretical and practical components, was conducted for the nurses to ensure proper weaning of neonates from mechanical ventilation.

RESULTS: The study group demonstrated a significant reduction in the use of surfactant replacement therapy post-extubation compared to the control group (p = 0.003). Additionally, infants in the study group experienced a statistically significant decrease in NICU hospitalization duration, total weaning time, and total ventilation period compared to the control group (p = 0.003, 0.0001, and 0.0001, respectively). Complications were markedly lower in the study group, with two-thirds of infants experiencing no complications, compared to 15.6% in the control group (p = 0.001). Moreover, re-intubation rates were significantly reduced in the study group compared to the control group (p = 0.1026).

CONCLUSION: These results highlight the effectiveness of the intervention in improving clinical outcomes for neonates, including reduced treatment needs, shorter hospital stays, and fewer complications.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40528182 | DOI:10.1186/s12912-025-03257-9