Multicenter Prospective Observational Cohort Study Research Articles

Association of Prenatal Exposure to Antiseizure Medications With Creative and Executive Function at Age 4.5 Years.

Neurodevelopmental effects of fetal antiseizure medication (ASM) exposure on creativity and executive functions are poorly understood. We previously found fetal valproate exposure to adversely affect measures of creativity and executive functions. In this study, we examine fetal exposure of newer ASMs on these functions in children of women with epilepsy (WWE) compared with children of healthy women (HW). The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study is a multicenter NIH-funded prospective observational cohort study of WWE and HW enrolled in pregnancy and their offsprings. This report examines blindly assessed creativity and executive functions in 4.5-year-old children of WWE vs HW. In addition, exposure-dependent ASM effects during the third trimester were examined in children of WWE, using a ratio of maximum observed ASM concentrations and ratio of defined daily dose (ratio DDD). For polytherapy, ratios were summed across ASMs. Linear regression models adjusted for multiple potential confounding factors were conducted for all analyses. The primary outcome for 4.5-year-old children was the Torrance Test of Creative Thinking-Figural Creativity Index. Secondary outcomes included the Global Executive Composite Score from the Behavior Rating Inventory of Executive Function-Preschool Version and subscales and other indexes of both measures. The primary analysis included 251 children of WWE and 73 of HW. No differences in creativity or executive function were found between children of WWE vs HW. No ASM exposure-dependent effects were found for the creativity measures, but exposure-dependent effects for executive function were present for ratio ASM concentration and ratio DDD. Our findings at 4.5 years show no differences in creative thinking between children of WWE vs HW (-3.2 [-9.0 to 2.7], p = 0.286) or associations with fetal exposure to ASMs (-2.6 [-11.0 to 5.7], p = 0.530). Secondary analyses revealed fetal exposure-dependent effects for executive function in children of WWE (7.0 [2.9-11.2], p = 0.001), which are most marked for levetiracetam (12.9 [4.2-21.6], p = 0.004). Our findings suggest that even for relatively safe ASMs, dosing needs to be adjusted to concentrations that prevent seizures, but balance risks to the fetus that high concentrations may pose. The study is registered at ClinicalTrials.gov as NCT01730170.

An MRI-based multi-parameter clinical decision support system (NeoMDSS) for early prediction of pathological complete response after the first cycle of neoadjuvant therapy in breast cancer: A multi-center prospective observational cohort study.

592 Background: Currently, there is no reliable and convenient way to predict response rates in early stages of neoadjuvant therapy (NAT) for breast cancer, which can affect the prognosis of non-responsive patients. Methods: In this prospective multi-center observational study, eligible participants who underwent NAT followed by radical surgery were recruited. All patients underwent magnetic resonance imaging (MRI) examination before and after the first cycle of NAT (1st-NAT). We analyzed the effects of clinicopathological features, such as histological grade, hormone receptor (HR) and HER2 status, Ki-67 expression, blood cell analysis, and MRI parameters including the reduction ratio of tumor diameter (ΔD%), apparent diffusion coefficient (ADC), and early enhancement ratio (EER) on NAT. By incorporating independent influencing factors, we developed a multiparametric clinical decision support system (NeoMDSS) model based on a retrospective cohort and validated its accuracy in both a prospective single-center internal cohort and a prospective multi-center external cohort. Relevant clinical trial details can be found under the identifier NCT04909554. Results: A total of 301 breast cancer patients were enrolled between January 2019 and December 2023, including 140 patients in the training cohort, 120 patients in the internal validation cohort, and 41 patients in the external validation cohort. The NeoMDSS model demonstrated excellent performance in predicting pathological complete response (pCR) at 1st-NAT, with an AUC of 0.874 (95% CI 0.813-0.935) in the training cohort, 0.845 (95% CI 0.771-0.919) in the internal validation cohort, and 0.867 (95% CI 0.742-0.992) in the external validation cohort. The NeoMDSS model exhibited a sensitivity, specificity, and accuracy of 80.0%, 81.3%, and 80.5%, respectively, in the internal validation cohort, and 87.0%, 83.3%, and 85.4%, respectively, in the external validation cohort. Calibration curves and decision curve analysis (DCA) further supported the clinical value of the NeoMDSS model. To facilitate the clinical application of the NeoMDSS model, a nomogram and an online website ( www.gdphneomdss.com ) were developed to calculate the probability of pCR, which the sensitivity, specificity, and accuracy of the NeoMDSS model were all 80.0% in the internal validation cohort and 80.0%, 81.3%, and 80.5% in the external validation cohort. Conclusions: The NeoMDSS model serves as a convenient tool in clinical practice at 1st-NAT to calculate and accurately predict the probability of pCR after NAT. This assists clinicians in determining whether to modify the treatment plan and improving personalized treatment for patients with poor response to NAT. Clinical trial information: NCT04909554 .

Snapshot Audit Early Onset Colorectal Cancer (EOCC) – What is the Current Situation in Switzerland?

Abstract Background Early onset colorectal cancer (EOCC), defined as colorectal cancer (CRC) ≤ 50 years, has seen an alarming rising incidence in western countries. Aims This research aims to determine the current state of incidence, symptoms, diagnostic methods, and treatment approach in EOCC compared to late onset CRC (LOCRC) in the extended Northwestern Switzerland. Methods Patients seeking care for CRC between April-November 2023 were enrolled in a prospective multicenter (11 hospitals within extended Northwestern Switzerland) observational cohort study. Information was collected using questionnaires and patient charts. Results We included 315 patients, thereof 38 (10.8%) EOCC. In total 211 (58.9%) patients were male, mean age was 42.5 and 71.2 years, respectively. Rectal bleeding was the main symptom in both groups (60.5% vs 37.0%), followed by change in bowel habits in EOCC and fatigue in LOCRC without reaching significance. Rectal bleeding and mucous, abdominal pain, change of bowel habits and bloating were significantly more often in EOCC. Significantly more LOCRC patients stated that their physical condition affected sexual erection and social interaction, whereas in EOCC, family life was significantly affected. For both groups, endoscopy was the leading diagnostic tool. EOCC had a diagnostic delay of 6.5 weeks compared to their counterparts. No difference in frequency of neoadjuvant treatment, surgical approach or need for emergency surgery was observed. In EOCC, a trend to more lymph node retrieval was observed and significantly more EOCC received an ostomy. Postoperatively, significantly more EOCC than LOCRC patients received adjuvant chemotherapy (55.6 % vs 28.6 %). Conclusion Our analysis illustrates the current standard-of-care of EOCC in the extended Northwestern Switzerland. EOCC compared to LOCRC patients present themselves differently to the medical community, leading to a different approach to their symptoms, which eventually results in a delayed diagnosis. Based on these results, it is time to foster awareness and start redefining national screening criteria.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p<0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected >90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Doppler ultrasound surveillance of recently formed haemodialysis arteriovenous fistula: the SONAR observational cohort study.

Arteriovenous fistulas are considered the best option for haemodialysis provision, but as many as 30% fail to mature or suffer early failure. To assess the feasibility of performing a randomised controlled trial that examines whether, by informing early and effective salvage intervention of fistulas that would otherwise fail, Doppler ultrasound surveillance of developing arteriovenous fistulas improves longer-term arteriovenous fistula patency. A prospective multicentre observational cohort study (the 'SONAR' study). Seventeen haemodialysis centres in the UK. Consenting adults with end-stage renal disease who were scheduled to have an arteriovenous fistula created. Participants underwent Doppler ultrasound surveillance of their arteriovenous fistulas at 2, 4, 6 and 10 weeks after creation, with clinical teams blinded to the ultrasound surveillance findings. Fistula maturation at week 10 defined according to ultrasound surveillance parameters of representative venous diameter and blood flow (wrist arteriovenous fistulas: ≥ 4 mm and > 400 ml/minute; elbow arteriovenous fistulas: ≥ 5 mm and > 500 ml/minute). Mixed multivariable logistic regression modelling of the early ultrasound scan data was used to predict arteriovenous fistula non-maturation by 10 weeks and fistula failure at 6 months. A total of 333 arteriovenous fistulas were created during the study window (47.7% wrist, 52.3% elbow). By 2 weeks, 37 (11.1%) arteriovenous fistulas had failed (thrombosed), but by 10 weeks, 219 of 333 (65.8%) of created arteriovenous fistulas had reached maturity (60.4% wrist, 67.2% elbow). Persistently lower flow rates and venous diameters were observed in those fistulas that did not mature. Models for arteriovenous fistulas' non-maturation could be optimally constructed using the week 4 scan data, with fistula venous diameter and flow rate the most significant variables in explaining wrist fistula maturity failure (positive predictive value 60.6%, 95% confidence interval 43.9% to 77.3%), whereas resistance index and flow rate were most significant for elbow arteriovenous fistulas (positive predictive value 66.7%, 95% confidence interval 48.9% to 84.4%). In contrast to non-maturation, both models predicted fistula maturation much more reliably [negative predictive values of 95.4% (95% confidence interval 91.0% to 99.8%) and 95.6% (95% confidence interval 91.8% to 99.4%) for wrist and elbow, respectively]. Additional follow-up and modelling on a subset (n = 192) of the original SONAR cohort (the SONAR-12M study) revealed the rates of primary, assisted primary and secondary patency arteriovenous fistulas at 6 months were 76.5, 80.7 and 83.3, respectively. Fistula vein size, flow rate and resistance index could identify primary patency failure at 6 months, with similar predictive power as for 10-week arteriovenous fistula maturity failure, but with wide confidence intervals for wrist (positive predictive value 72.7%, 95% confidence interval 46.4% to 99.0%) and elbow (positive predictive value 57.1%, 95% confidence interval 20.5% to 93.8%). These models, moreover, performed poorly at identifying assisted primary and secondary patency failure, likely because a subset of those arteriovenous fistulas identified on ultrasound surveillance as at risk underwent subsequent successful salvage intervention without recourse to early ultrasound data. Although early ultrasound can predict fistula maturation and longer-term patency very effectively, it was only moderately good at identifying those fistulas likely to remain immature or to fail within 6 months. Allied to the better- than-expected fistula patency rates achieved (that are further improved by successful salvage), we estimate that a randomised controlled trial comparing early ultrasound-guided intervention against standard care would require at least 1300 fistulas and would achieve only minimal patient benefit. This trial is registered as ISRCTN36033877 and ISRCTN17399438. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR135572) and is published in full in Health Technology Assessment; Vol. 28, No. 24. See the NIHR Funding and Awards website for further award information.

Study protocol: the biologics in severe chronic rhinosinusitis with nasal polyps survey

IntroductionChronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids,...

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

COVID-19 associated pulmonary aspergillosis in critically-ill patients: a prospective multicenter study in the era of Delta and Omicron variants

BackgroundDuring the first COVID-19 pandemic wave, COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in up to 11–28% of critically ill COVID-19 patients and associated with increased mortality. As new SARS-CoV-2 variants emerged, the characteristics of critically ill COVID-19 patients have evolved, particularly in the era of Omicron. The purpose of this study is to investigate the characteristics of CAPA in the era of new variants.MethodsThis is a prospective multicenter observational cohort study conducted in France in 36 participating intensive care units (ICU), between December 7th, 2021 and April 26th 2023. Diagnosis criteria of CAPA relied on European Confederation of Medical Mycology (ECMM)/International Society for Human & Animal Mycology (ISHAM) consensus criteria.Results566 patients were included over the study period. The prevalence of CAPA was 5.1% [95% CI 3.4–7.3], and rose to 9.1% among patients who required invasive mechanical ventilation (IMV). Univariable analysis showed that CAPA patients were more frequently immunosuppressed and required more frequently IMV support, vasopressors and renal replacement therapy during ICU stay than non-CAPA patients. SAPS II score at ICU admission, immunosuppression, and a SARS-CoV-2 Delta variant were independently associated with CAPA in multivariable logistic regression analysis. Although CAPA was not significantly associated with day-28 mortality, patients with CAPA experienced a longer duration of mechanical ventilation and ICU stay.ConclusionThis study contributes valuable insights into the prevalence, characteristics, and outcomes of CAPA in the era of Delta and Omicron variants. We report a lower prevalence of CAPA (5.1%) among critically-ill COVID-19 patients than previously reported, mainly affecting intubated-patients. Duration of mechanical ventilation and ICU stay were significantly longer in CAPA patients.

Short-term outcomes of a multicentre prospective study using a "visible" polyvinylidene fluoride onlay mesh for the prevention of midline incisional hernia.

Prophylactic meshes in high-risk patients prevent incisional hernias, although there are still some concerns about the best layer to place them in, the type of fixation, the mesh material, the significance of the level of contamination, and surgical complications. We aimed to provide answers to these questions and information about how the implanted material behaves based on its visibility under magnetic resonance imaging (MRI). This is a prospective multicentre observational cohort study. Preliminary results from the first 3months are presented. We included general surgical patients who had at least two risk factors for developing an incisional hernia. Multivariate logistic regression was used. A polyvinylidene fluoride (PVDF) mesh loaded with iron particles was used in an onlay position. MRIs were performed 6weeks after treatment. Between July 2016 and June 2022, 185 patients were enrolled in the study. Surgery was emergent in 30.3% of cases, contaminated in 10.7% and dirty in 11.8%. A total of 5.6% of cases had postoperative wound infections, with the requirement of stoma being the only significant risk factor (OR = 7.59, p = 0.03). The formation of a seroma at 6weeks detected by MRI, was associated with body mass index (OR = 1.13, p = 0.02). The prophylactic use of onlay PVDF mesh in midline laparotomies in high-risk patients was safe and effective in the short term, regardless of the type of surgery or the level of contamination. MRI allowed us to detect asymptomatic seromas during the early process of integration. This protocol was registered at ClinicalTrials.gov (NCT03105895).

Urinary Biomarkers for Cell Cycle Arrest TIMP-2 and IGFBP7 for Prediction of Graft Function Recovery after Kidney Transplantation.

TIMP-2 and IGFBP7 have been identified and validated for the early detection of renal injury in critically ill patients, but data on recovery of allograft function after kidney transplantation (KTx) are scarce. In a prospective observational multicenter cohort study of renal transplant recipients, urinary [TIMP-2] × [IGFBP7] was evaluated daily from day 1 to 7 after KTx. Different stages of early graft function were defined: immediate graft function (IGF) (decrease ≥ 10% in serum creatinine (s-crea) within 24 h post KTx); slow graft function (SGF) (decrease in s-crea < 10% within 24 h post KTx); and delayed graft function (DGF) (any dialysis needed within the first week after KTx). A total of 186 patients were analyzed. [TIMP-2] × [IGFBP7] was significantly elevated as early as day 1 in patients with DGF compared to SGF and IGF. ROC analysis of [TIMP-2] × [IGFBP7] at day 1 post-transplant for event "Non-DGF" revealed a cut-off value of 0.9 (ng/mL)2/1000 with a sensitivity of 87% and a specificity of 71%. The positive predictive value for non-DGF was 93%. [TIMP-2] × [IGFBP7] measured at day 1 after KTx can predict early recovery of transplant function and is therefore a valuable biomarker for clinical decision making.

Association of socioeconomic deprivation with outcomes in critically ill adult patients: an observational prospective multicenter cohort study.

The influence of socioeconomic deprivation on health inequalities is established, but its effect on critically ill patients remains unclear, due to inconsistent definitions in previous studies. Prospective multicenter cohort study conducted from March to June 2018 in eight ICUs in the Greater Paris area. All admitted patients aged ≥ 18years were enrolled. Socioeconomic phenotypes were identified using hierarchical clustering, based on education, health insurance, income, and housing. Association of phenotypes with 180-day mortality was assessed using Cox proportional hazards models. A total of 1,748 patients were included. Median age was 62.9 [47.4-74.5] years, 654 (37.4%) patients were female, and median SOFA score was 3 [1-6]. Study population was clustered in five phenotypes with increasing socioeconomic deprivation. Patients from phenotype A (n = 958/1,748, 54.8%) were without socioeconomic deprivation, patients from phenotype B (n = 273/1,748, 15.6%) had only lower education levels, phenotype C patients (n = 117/1,748, 6.7%) had a cumulative burden of 1[1-2] deprivations and all had housing deprivation, phenotype D patients had 2 [1-2] deprivations, all of them with income deprivation, and phenotype E patients (n = 93/1,748, 5.3%) included patients with 3 [2-4] deprivations and included all patients with health insurance deprivation. Patients from phenotypes D and E were younger, had fewer comorbidities, more alcohol and opiate use, and were more frequently admitted due to self-harm diagnoses. Patients from phenotype C (predominant housing deprivation), were more frequently admitted with diagnoses related to chronic respiratory diseases and received more non-invasive positive pressure ventilation. Following adjustment for age, sex, alcohol and opiate use, socioeconomic phenotypes were not associated with increased 180-day mortality: phenotype A (reference); phenotype B (hazard ratio [HR], 0.85; 95% confidence interval CI 0.65-1.12); phenotype C (HR, 0.56; 95% CI 0.34-0.93); phenotype D (HR, 1.09; 95% CI 0.78-1.51); phenotype E (HR, 1.20; 95% CI 0.73-1.96). In a universal health care system, the most deprived socioeconomic phenotypes were not associated with increased 180-day mortality. The most disadvantaged populations exhibit distinct characteristics and medical conditions that may be addressed through targeted public health interventions.

Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study

IntroductionTrauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed...

Quality of Life in Patients Undergoing Emergency Surgery for Complex Colorectal Cancer: Protocol and Piloting of the Surgical Utilization and Recovery Patterns for Advanced Stage Colorectal Cancer Study.

Introduction: Globally, cancer is the leading cause of mortality, with colorectal neoplasia ranking third in terms of incidence and mortality worldwide. Patients face disease- and treatment-specific impacts, which can significantly influence their quality of life (QoL). Aim: This study aimed to propose a protocol to measure in-hospital and long-term QoL in patients with complicated colorectal cancer (CRC). Material and Methods: multicenter prospective observational cohort study. Results: QoL is a multidimensional concept that includes criteria for physical, mental, emotional, and social functionality as perceived by the patient. Periodically evaluating QoL offers measurable and objective tools to intervene at the appropriate time to decrease the Years of Life Lost and Years Lived with Disabilities for CRC patients. However, a structured and functional system requires dedicated and common institutional effort. A pilot study using this protocol included 69 patients, 65.12+-10.92 years, M:F ratio = 56.5:43.5%. Surgical procedure was right hemicolectomy, left colectomy, transverse colectomy, sigmoidectomy, total colectomy, rectal resection, and colorectal resection with stoma (ileostomy or colostomy) in 21.7%, 11.6%, 2.9%, 11.6%, 1.4%, 23.2%, and 27.5% of the cases, respectively. The mean Global Health Status Score, Symptom Score, and Functional Score was 82.36+-18.60, 11.89+-10.27, and 86.27, 74.50-94.11, respectively. Conclusions: CRC diagnosis has major effects on patients physical and psychological status, and concentrated efforts should be made by the involved medical team and healthcare systems to improve QoL throughout the treatment pathway.

Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China

Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited. In this multicenter, prospective observational cohort study, we described the diagnostic efficacy of pathogen-targeted NGS (ptNGS) and metagenomic NGS (mNGS) compared to that of composite microbiologic assays, for infectious meningitis/encephalitis (M/E). In total, 152 patients diagnosed with clinically suspected M/E at four tertiary hospitals were enrolled; ptNGS and mNGS were used in parallel for pathogen detection in CSF. Among the 89 patients who were diagnosed with definite infectious M/E, 57 and 39 patients had causal microbial detection via ptNGS and mNGS, respectively. The overall accuracy of ptNGS was 65.1%, with a positive percent agreement (PPA) of 64% and a negative percent agreement (NPA) of 66.7%; and the overall accuracy of mNGS was 47.4%, with a PPA of 43.8% and an NPA of 52.4% after discrepancy analysis. There was a significant difference in the detection efficiency between these two methods both for PPA (sensitivity) and overall accuracy for pathogen detection (P<0.05). NGS tests have provided new information in addition to conventional microbiologic tests. ptNGS seems to have superior performance over mNGS for common causative pathogen detection in CSF for infectious M/E.

Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero

Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. A total of 102 participants (vedolizumab, n= 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n= 32) than ustekinumab (14 wk; range, 9-36 wk; n= 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

Instrumental activities of daily living in older patients with metastatic prostate cancer: results from the meet-URO network ADHERE prospective study

Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients’ IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5—ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28–37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs.

Prospective evaluation and follow-up of nutritional status of children hospitalized in secondary-care level hospitals: a multicentre study.

Although disease-associated undernutrition is still an important problem in hospitalized children that is often underrecognized, follow-up studies evaluating post-discharge nutritional status of children with undernutrition are lacking. The aim of this multicentre prospective observational cohort study was to assess the rate of acute undernutrition (AU) and/or having a high nutritional risk (HR) in children on admission to seven secondary-care level Dutch hospitals and to evaluate the nutritional course of AU/HR group during admission and post-discharge. STRONGkids was used to indicate HR, and AU was based on anthropometric data (z-score < -2 for weight-for-age (WFA; <1 year) or weight-for-height (WFH; ≥1 year)). In total, 1985 patients were screened for AU/HR over a 12-month period. On admission, AU was present in 9.9% of screened children and 6.2% were classified as HR; 266 (13.4%) children comprised the AU/HR group (median age 2.4 years, median length of stay 3 days). In this group, further nutritional assessment by a dietitian during hospitalization occurred in 44% of children, whereas 38% received nutritional support. At follow-up 4-8 weeks post-discharge, 101 out of orginal 266 children in the AU/HR group (38%) had available paired anthropometric measurements to re-assess nutrition status. Significant improvement of WFA/WFH compared to admission (-2.48vs. -1.51 SD; p<0.001) and significant decline in AU rate from admission to outpatient follow-up (69.3%vs. 35.6%; p<0.001) were shown. In conclusion, post-discharge nutritional status of children with undernutrition and/or high nutritional risk on admission to secondary-care level pediatric wards showed significant improvement, but about one-third remained undernourished. Findings warrant the need for a tailored post-discharge nutritional follow-up.

Let's Agree to Disagree on Operative Versus Nonoperative Treatment for Distal Radius Fractures in Older People: Protocol for a Prospective International Multicenter Cohort Study.

Distal radius fractures are the most frequently encountered fractures in Western societies, typically affecting patients aged 50 years and older. Although this is a common injury, the best treatment for these fractures in older patients is still under debate. This prospective study aims to compare the outcome of operatively and nonoperatively treated distal radius fractures in the older population. Only patients with distal radius fractures for which equipoise regarding the optimal treatment exists will be included. This prospective international multicenter observational cohort study will be designed as a natural experiment. Natural experiments are observational studies in which treatment allocation is determined by factors outside the control of the investigators but also (largely) independent of patient characteristics. Patients aged 65 years and older with an acute distal radius fracture will be considered for inclusion. Treatment allocation (operative vs nonoperative) will be based on the local preferences of the treating hospital either in Switzerland or the Netherlands. Hence, the process governing treatment allocation resembles that of randomization. Patients will be identified after treatment has been initiated. Based on the radiographs and baseline information of the patient, an expert panel of 6 certified trauma surgeons from 2 regions will provide their treatment recommendation. Only patients for whom the experts disagree on treatment recommendations will ultimately be included in the study (ie, for whom there is a clinical equipoise). For these patients, both operative and nonoperative treatment of distal radius fractures are viable, and treatment choice is predominantly determined by personal or local preference. The primary outcome will be the Patient-Rated Wrist Evaluation score at 12 weeks. Secondary outcomes will include the Physical Activity Score for the Elderly, the EQ questionnaire, pain, the living situation, range of motion, complications, and radiological outcomes. By including outcomes such as living situation and the Physical Activity Score for the Elderly, which are not relevant for younger cohorts, valuable information to tailor treatment to the needs of the older population can be gained. According to the sample size collection, which was based on the minimal important clinical difference of the Patient-Rated Wrist Evaluation, 92 patients will have to be included, with at least 46 patients in each treatment group. Enrollment began in July 2023 and is expected to continue until summer 2024. The final follow-up will be 2 years after the last patient is included. Although many trials on this topic have previously been published, there remains an ongoing debate regarding the optimal treatment for distal radius fractures in older patients. This observational study, which will use a fairly new methodological study design, will provide further information on treatment outcomes for older patients with distal radius fractures for which to date equipoise exists regarding the optimal treatment. DERR1-10.2196/52917.

Japanese Study of the Effects of AMG (α1-Microglobulin) Reduction Rates on Survival (JAMREDS): A Protocol of a Multicenter Prospective Observational Cohort Study

Introduction: Recent advances in dialysis therapy have made it possible to remove middle molecules. Removal of small-middle molecules, such as β2-microglobulin, can now be achieved with conventional hemodialysis (HD), and removal of large-middle molecules has become a target, particularly for α1-microglobulin (AMG, 33 kD). The AMG reduction rate has emerged as a target for improvement of various clinical symptoms, but the effects on prognosis have yet to be determined. The “Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival” (JAMREDS) was started in April 2020, with the goal of determining if the AMG reduction rate associates with the risk of mortality and cardiovascular disease (CVD) events. Methods: JAMREDS is a prospective observational study in patients on HD to examine the effects of: (1) AMG reduction rate on survival outcome and CVD events; (2) dialysis treatment modalities (HD, intermittent infusion hemodiafiltration(iHDF), pre/post-dilution online HDF) on survival and CVD events (based on AMG reduction rates with treatment mode); and (3) AMG reduction rates on survival and CVD events in patients undergoing each therapy (iHDF, pre/post-dilution online HDF). The number of planned subjects was 4,000 in preplanning. Data are collected using RED-Cap, which is an EDC system. A total of 9,930 patients were enrolled at the beginning of the study at 59 registered facilities. The JAMREDS observation period will continue until the end of 2023, after which the data will be cleaned and confirmed before analysis. Conclusion: This study may provide new evidence for the relationship between the amount of removed large-middle molecules (such as AMG) and the mortality and CVD risk. Comparisons with convection volumes will also be of interest.

Anterior vs Posterior Surgery for Patients With Degenerative Cervical Myelopathy: An Observational Study From the Canadian Spine Outcomes and Research Network.

The advantages and disadvantages of anterior vs posterior surgical approaches for patients with progressive degenerative cervical myelopathy (DCM) remain uncertain. Our primary objective was to evaluate patient-reported disability at 1 year after surgery. Our secondary objectives were to evaluate differences in patient profiles selected for each approach in routine clinical practice and to compare neurological function, neck and arm pain, health-related quality of life, adverse events, and rates of reoperations. We analyzed data from patients with DCM who were enrolled in an ongoing multicenter prospective observational cohort study. We controlled for differences in baseline characteristics and numbers of spinal levels treated using multivariable logistic regression. Adverse events were collected according to the Spinal Adverse Events Severity protocol. Among 559 patients, 261 (47%) underwent anterior surgery while 298 (53%) underwent posterior surgery. Patients treated posteriorly had significantly worse DCM severity and a greater number of vertebral levels involved. After adjusting for confounders, there was no significant difference between approaches for odds of achieving the minimum clinically important difference for the Neck Disability Index (odds ratio 1.23, 95% CI 0.82 to 1.86, P = .31). There was also no significant difference for change in modified Japanese Orthopedic Association scores, and differences in neck and arm pain and health-related quality of life did not exceed minimum clinically important differences. Patients treated anteriorly experienced greater rates of dysphagia, whereas patients treated posteriorly experienced greater rates of wound complications, neurological complications, and reoperations. Patients selected for posterior surgery had worse DCM and a greater number of vertebral levels involved. Despite this, anterior and posterior surgeries were associated with similar improvements in disability, neurological function, pain, and quality of life. Anterior surgery had a more favorable profile of adverse events, which suggests it might be a preferred option when feasible.