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Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016:A Nationwide Cohort From The Netherlands
No full textIntroduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients. Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers. Data including patient and tumor characteristics, radiological and pathological reports and oncological follow-up outcomes were gathered from documentation in electronic patient files for patients who underwent a curative resection for primary rectal cancer in 2016. MMR-status was verified in pathology reports from immunohistochemistry or PCR microsatellite instability testing. Results: MMR-status was determined in 1645 (54.9%) of 3001 stage I-IV rectal cancer patients, of which 46 (2.8%) were dMMR. Median follow up was 50 months (IQR 38-55). MMR-status was determined more often in younger patients. DMMR tumors were more locally advanced (cT4 23.9% vs. 8.8%, P =.010), and more distally located (mean distance to anorectal junction 3.6 cm vs. 5.3 cm, P =.004) than pMMR tumors. While radiological response after neoadjuvant (chemo)radiotherapy was similar, pathological complete response was significantly higher in dMMR compared to pMMR tumors (24.0% vs. 10.0%, P =.039). Four-year local recurrence, distant metastases, cancer-specific or overall survival rate between patients with dMMR or pMMR tumors were similar. Conclusion: In this population-based cohort, 2.8% of rectal cancers in which MMR-status was determined were subtyped as dMMR. Surprisingly, dMMR was associated with higher pathological complete response rate to neoadjuvant (chemo) radiotherapy than pMMR. MMR-status did not impact oncological outcomes
Adaptation and psychometric assessment of the postpartum childcare stress checklist among Arab women in the United Arab Emirates
No full textProblem: There is currently no validated version of the Postpartum Childcare Stress Checklist (PCSC) in the context of Arabic-speaking women in the United Arab Emirates (UAE). Background: The postpartum period is a transformative phase in a woman's life, during which mothers are highly vulnerable to mental health problems, compounded by childcare demands. Childcare stress is a strong predictor of postpartum depression. Thus, there is a need for a validated Arabic measure of childcare stress. Aim: This study aims to translate and psychometrically evaluate the Arabic version of the PCSC among mothers residing in the UAE. Methods: The PCSC was psychometrically assessed in a cohort of 399 women in the UAE between February 2017 and September 2018. Using best practices in instrument translation; psychometric evaluation included item-test and item-total correlations, confirmatory factor analysis, tests at two-time points, and validity tests. Results: The analysis produced a 19-item scale in both unidimensional and multidimensional formats, with Geomin rotated factor loadings ranging from 0.31 to 0.84 and an average variance of 0.46, demonstrating adequate validity. The Arabic PCSC had acceptable reliability coefficients at three (a= = 0.79) and six (a=0.80) months and adequate concurrent and predictive validity at three and six months postpartum. Discussion: Childcare stress is an internationally reliable and validated construct. The PCSC was also positively correlated with depressive and anxiety symptoms. Conclusion: The Arabic PCSC is a psychometrically validated measure which can be used in future Arabic-language studies and may lead to improved interventions for maternal mental health across Arab-speaking communities
Objective outcome prediction in depression through functional MRI brain network dynamics
No full textResearch purpose: Subjective clinical decision-making in major depressive disorder (MDD) may result in low treatment effectiveness. This study aims to identify objective predictors of MDD outcome using resting-state functional MRI scans, acquired from 25 MDD patients at baseline. Over a year, patients were assessed every 3 months, labeled as positive or negative outcome (change in depression severity). Group independent component analysis (GICA) identified (sub)networks at different orders, from which static and dynamic (wavelet) fMRI features were extracted. Binary classifiers performed MDD outcome prediction at each follow-up. Principal Results: The total coherence feature, reflecting network interactivity, yielded the highest performance (area under the curve (AUC) of 0.70). In the positive outcome group, total coherence between the default mode network and ventral salience network was increased at all follow-ups. Classification using this feature alone further demonstrated its discriminating capability (AUC of 0.76 ± 0.10 over all follow-ups). These results suggest that a higher switching capability between internal and external brain states predicts symptom improvement. Higher GICA orders, where major networks are divided into subnetworks, yielded optimal classification performance. Major Conclusions: Total coherence, a dynamic fMRI measure, achieved the highest classification performance. These findings contribute to the identification of prognostic biomarkers in MDD
Use patterns of classic, novel, and herbal opioids
No full textBackground: Data on use patterns and psychological and physical effects of novel synthetic opioids (NSOs) and herbal opioids like kratom (Mitragyna speciosa) lags behind that of classic opioids. Aims: This study aimed to describe use patterns, adverse events, subjective experience and motivation of use with classic, novel and herbal opioids. Methods: A two-part survey was used. The first part examined the prevalence, use patterns (dosage, administration route, duration of effects), and associated adverse events of classic, novel and herbal opioids. The second part delved into detailed retrospective experiences of survey responders with an opioid of preferred choice, mostly kratom. Results: Between May 2020 and February 2023, 467 respondents started the survey, of which 310 met the inclusion criteria. Of these, 52 % (N = 161) completed the first part, 65.6 % (N = 105) started the second part of which 72 completed. Most respondents were male, highly educated, based in North America or Europe, often using multiple opioids. A total of twenty-seven different compounds were reported, of which hydrocodone/dihydrocodeine, kratom, acetylfentanyl, and U-47700 were used the most. A wide range of doses was reported for each compound. Median effect durations ranged between 3 and 4 h for most of the compounds. Administration routes varied, with oral intake being most prevalent. Fentanyl analogues were often administered intravenously. Physical/psychological adverse events were frequently reported by users of oxycodone, kratom, acetylfentanyl, and U-47700. User reports revealed that both kratom and classic opioids were used for recreational and medical purposes, including ameliorating pain, addiction/withdrawal, anxiety, and mood enhancement. Conclusion: Psychological and physical adverse events were widely present among classic, novel and herbal opioids suggesting a need for risk monitoring worldwide. Similarities between classic opioids and kratom include medical utility as well as addictive potential
Impact of Inflammation After Cardiac Surgery on 30-Day Mortality and Machine Learning Risk Prediction
No full textObjectives: To investigate the impact of systemic inflammatory response syndrome (SIRS) on 30-day mortality following cardiac surgery and develop a machine learning model to predict SIRS. Design: Retrospective cohort study. Setting: Single tertiary care hospital. Participants: Patients who underwent elective or urgent cardiac surgery with cardiopulmonary bypass (CPB) from 2016 to 2020 (N = 1,908). Interventions: Mixed cardiac surgery operations were performed on CPB. Data analysis was made of preoperative, intraoperative, and postoperative variables without direct interventions. Measurements and Main Results: SIRS, defined using American College of Chest Physicians/Society of Critical Care Medicine parameters, was assessed on the first postoperative day. The primary outcome was 30-day mortality. SIRS incidence was 28.7%, with SIRS-positive patients showing higher 30-day mortality (12.2% v 1.5%, p < 0.001). A multivariate logistic model identified predictors of SIRS. Propensity score matching balanced 483 patient pairs. SIRS was associated with increased mortality (OR 2.77; 95% CI 1.40-5.47, p = 0.003). Machine learning models to predict SIRS were developed. The baseline risk model achieved an area under the curve of 0.77 ± 0.04 in cross-validation and 0.73 (95% CI 0.70-0.85) on the test set, while the procedure-adjusted risk model showed improved performance with an area under the curve of 0.81 ± 0.02 in cross-validation and 0.82 (95% CI 0.76-0.85) on the test set. Conclusions: SIRS is significantly associated with increased 30-day mortality following cardiac surgery. Machine learning models effectively predict SIRS, paving the way for future investigations on potential targeted interventions that may mitigate adverse outcomes.</p
Higher Versus Lower Protein Delivery in Critically Ill Patients:A Systematic Review and Bayesian Meta-Analysis
No full textOBJECTIVES: Recent multicenter trials suggest that higher protein delivery may result in worse outcomes in critically ill patients, but uncertainty remains. An updated Bayesian meta-analysis of recent evidence was conducted to estimate the probabilities of beneficial and harmful treatment effects. DATA SOURCES: An updated systematic search was performed in three databases until September 4, 2024. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and the protocol was preregistered in PROSPERO (CRD42024546387). STUDY SELECTION: Randomized controlled trials that studied adult critically ill patients comparing protein doses delivered enterally and/or parenterally with similar energy delivery between groups were included. DATA EXTRACTION: Data extraction was performed by two authors independently, using a predefined worksheet. The primary outcome was mortality. Posterior probabilities of any benefit (relative risk [RR] < 1.00) or harm (RR > 1.00) and other important beneficial and harmful effect size thresholds were estimated. Risk of bias assessment was performed using the risk of bias 2.0 tool. All analyses were performed using a Bayesian hierarchical random-effects models, under vague priors. DATA SYNTHESIS: Twenty-two randomized trials (n = 4164 patients) were included. The mean protein delivery in the higher and lower protein groups was 1.5 ± 0.6 vs. 0.9 ± 0.4g/kg/d. The median RR for mortality was 1.01 (95% credible interval, 0.84-1.16). The posterior probability of any mortality benefit from higher protein delivery was 43.6%, while the probability of any harm was 56.4%. The probabilities of a 1% (RR < 0.99) and 5% (RR < 0.95) mortality reduction by higher protein delivery were 38.7% and 22.9%, respectively. Conversely, the probabilities of a 1% (RR > 1.01) and 5% (RR > 1.05) mortality increase were 51.5% and 32.4%, respectively. CONCLUSIONS: There is a considerable probability of an increased mortality risk with higher protein delivery in critically ill patients, although a clinically beneficial effect cannot be completely eliminated based on the current data
Revising EU pharmaceutical legislation:will it foster drug repurposing?
No full textRepurposing off-patent drugs can be a potential source of low-cost treatments for patients with unmet medical needs. Here, we review the proposed new European Union (EU) pharmaceutical legislation in which two articles address drug repurposing. We find certain barriers hindering the adoption of these new incentives by academic and not-for-profit stakeholders, including lack of knowledge on regulatory aspects, pharmacovigilance, and restrictions in data protection. To further empower the intended stakeholders of the legislation, these initiatives can be strengthened by creating additional scientific, regulatory, and health technology assessment (HTA) support for not-for-profit repurposers, and by determining fair data protection periods and pricing policies. To support drug repurposing, Europe should work toward a comprehensive drug-repurposing strategy that fosters the repurposing of generic, shelved, and protected drugs
Advanced Imaging and Preoperative MR-Based Cinematic Rendering Reconstructions for Neoplasms in the Oral and Maxillofacial Region
No full textThis case study highlights the use of cinematic rendering (CR) in preoperative planning for the excision of a cyst in the oral and maxillofacial region of a 60-year-old man. The patient presented with a firm, non-tender mass in the right cheek, clinically suspected to be an epidermoid cyst. Conventional imaging, including dental magnetic resonance imaging (MRI) protocols, confirmed the lesion's size, location, and benign nature. CR reconstructions, combining advanced algorithms and novel skin presets, allow for the generation of highly realistic, three-dimensional visualizations from conventional imaging datasets. CR provided an enhanced, detailed depiction of the lesion within its anatomical context, significantly improving spatial understanding for surgical planning. The surgical excision was performed without complications, and histological analysis confirmed the diagnosis of a benign epidermoid cyst with no evidence of dysplasia or malignancy. This case demonstrates the potential of CR to refine preoperative planning, especially in complex anatomical regions such as the face and jaw, by offering superior visualization of superficial and deep structures. Thus, the integration of CR into clinical workflows has the potential to lead to improved diagnostic accuracy and better surgical outcomes
OPtimal TIming of antenatal COrticosteroid administration in pregnancies complicated by early-onset fetal growth REstriction:results of a large, multicenter cohort study (the OPTICORE study)
No full textBackground: Early-onset fetal growth restriction as consequence of placental insufficiency frequently requires iatrogenic preterm birth. Administration of antenatal corticosteroids reduces risks of neonatal morbidity and mortality following preterm birth and is most beneficial if the neonate is delivered within 2 weeks following treatment. International guidelines on fetal growth restriction pregnancies do not provide directives regarding the timing of antenatal corticosteroids, resulting in practice variation. Objective: This study compared the 2 main timing strategies of antenatal corticosteroids administration in the Netherlands for early-onset fetal growth restriction pregnancies: administration when the umbilical artery shows a pulsatility index above the 95th centile with (A) positive end-diastolic flow vs (B) absent or reversed end-diastolic velocity. Study Design: A multicenter retrospective cohort study was performed in 6 tertiary hospitals in the Netherlands between 2012 and 2021. Three hospitals practiced timing strategy A and 3 strategy B. The primary outcome was defined as a composite of perinatal and in-hospital mortality. Secondary outcomes were in line with the core outcome set for fetal growth restriction. Mixed effects analyses were performed adjusted for birthweight z-score and gestational age at birth to compare the 2 timing strategies. Results: A total of 1453 patients were included, of whom 871 and 582 were treated according to timing strategy A and B, respectively. Corticosteroids were administered at a mean gestational age of 28 weeks and 3 days (standard deviation 16.0 days) in timing strategy A and 28 weeks and 4 days (standard deviation 15.8 days) in timing strategy B. The median birthweights were 1050 (range 795, 1350) and 1060 (range 801, 1339) in timing strategy A and B, respectively. Although not statistically significant, rates of perinatal and in-hospital mortality were increased in timing strategy B infants (7.2% vs 9.8%; adjusted odds ratio 1.47; 95% confidence interval 0.97–2.22, reference A). 52.8% and 53.6% of patients in strategy A and B, respectively, delivered within the corticosteroids therapeutic window of 2 to 14 days (P value .663), with a median time between corticosteroid administration and delivery of 6 days for strategy A and 6 days for strategy B. Timing strategy B was associated with more necrotizing enterocolitis (3.7% vs 7.6%; adjusted odds ratio 2.18; 95% confidence interval 1.29–3.69), but less respiratory distress syndrome (39.6% vs 34.5%; adjusted odds ratio 0.63; 95% confidence interval 0.45–0.88) and bronchopulmonary dysplasia (18.9% vs 17.4%; adjusted odds ratio 0.69; 95% confidence interval 0.50–0.96). Other outcomes were similar between groups. Conclusion: Timing strategy B seemed to be associated with higher rates of the composite of perinatal and in-hospital mortality, which could not be explained by a difference in time intervals between corticosteroid administration and delivery. Importantly, most pregnant women delivered outside the presumed therapeutic corticosteroid window. Future research should focus on the improvement of the timing of antenatal corticosteroids in pregnancies complicated by early-onset fetal growth restriction and the identification of other differences in ante- and/or postnatal management to explain differences in outcomes, given the high risk for neonatal morbidity and mortality in this setting.</p
Barriers and facilitators for adequate calcium intake during pregnancy:A mixed methods study
No full textOBJECTIVE: This study evaluates the effectiveness of calcium supplementation as a preventive measure for pregnant women with insufficient calcium intake, examining adherence to the recommended 1000 mg daily intake and identifying influencing factors. METHODS: A survey (Expect cohort II, n = 823) evaluated calcium adherence among pregnant women, followed by interviews with sixteen purposefully selected participants. Verbatim transcripts were independently analyzed to identify key themes. RESULTS: Among survey participants, 82 % discussed the importance of calcium intake, with 83 % expressing intent to improve intake. Of those counselled on calcium, 48 % had insufficient intake, compared to 64 % without counseling. Facilitators included perceived safety, maternal motivation to keep child safe, trust in professionals, supportive environments, and increased awareness. Obstacles included lack of knowledge on calcium sources, pill dosage, low intrinsic motivation, information comprehension and novelty of the advice. CONCLUSION: Despite of awareness raising efforts through counseling, only half of the women reached adequate calcium levels, with interviews revealing limited understanding. Clear messages on calcium benefits, dispelling concerns about potential harm, and offering concrete guidance can improve intake. Repetition of advice and increase publicity can normalize and enhance acceptability of calcium consumption during pregnancy