Pooled Data Research Articles

Compression-only versus standard cardiopulmonary resuscitation in out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials.

Bystander-initiated cardiopulmonary resuscitation (CPR) can improve survival rates in individuals with out-of-hospital cardiac arrest (OHCA). Two CPR approaches are commonly utilized, standard (S-CPR) with mouth-to-mouth breathing and compression-only (CO-CPR). We conducted a systematic review and meta-analysis to compare clinical outcomes associated with S-CPR versus CO-CPR in OHCA. A systematic literature search was conducted using PubMed, EMBASE, and the Cochrane Library. Eligible studies included randomized controlled trials (RCTs) focused on adult OHCA patients receiving CO-CPR or S-CPR. Forest plots were generated for pooled data analysis using Review Manager version 5.4. Random-effect analyses were used, and statistical significance was set at p < .05. Four randomized controlled trials were included in the final analysis, encompassing a total sample size of 4987 patients (2482 in the CO-CPR group and 2505 in the S-CPR group). CO-CPR was associated with significantly improved 1-day survival compared with S-CPR (OR = 1.15; 95% CI: 1.02-1.31; p = .03) and survival to hospital discharge (OR = 1.25; 95% CI: 1.01-1.55; p = .04). No heterogeneity was observed among the studies for either outcome. CO-CPR emerges as a promising strategy for improving outcomes in OHCA compared to S-CPR. However, further large-scale RCTs are required to generate more robust evidence.

Composite activity type and stride-specific energy expenditure estimation model for thigh-worn accelerometry

BackgroundAccurately measuring energy expenditure during physical activity outside of the laboratory is challenging, especially on a large scale. Thigh-worn accelerometers have gained popularity due to the possibility to accurately detect physical activity types. The use of machine learning techniques for activity classification and energy expenditure prediction may improve accuracy over current methods. Here, we developed a novel composite energy expenditure estimation model by combining an activity classification model with a stride specific energy expenditure model for walking, running, and cycling.MethodsWe first trained a supervised deep learning activity classification model using pooled data from available adult accelerometer datasets. The composite energy expenditure model was then developed and validated using additional data based on a sample of 69 healthy adult participants (49% female; age = 25.2 ± 5.8 years) who completed a standardised activity protocol with indirect calorimetry as the reference measure.ResultsThe activity classification model showed an overall accuracy of 99.7% across all five activity types during validation. The composite model for estimating energy expenditure achieved a mean absolute percentage error of 10.9%. For running, walking, and cycling, the composite model achieved a mean absolute percentage error of 6.6%, 7.9% and 16.1%, respectively.ConclusionsThe integration of thigh-worn accelerometers with machine learning models provides a highly accurate method for classifying physical activity types and estimating energy expenditure. Our novel composite model approach improves the accuracy of energy expenditure measurements and supports better monitoring and assessment methods in non-laboratory settings.

Genetically predicted metabolites mediate the association between lipidome and malignant melanoma of skin.

To investigate the causal relationship between lipidome and malignant melanoma of skin (MMOS), while identifying and quantifying the role of metabolites as potential mediators. A two-sample Mendelian randomization (MR) analysis of lipid species (n=7174) and MMOS was performed using pooled data from genome-wide association studies (GWAS). In addition, we quantified the proportion of metabolite-mediated lipidome effects on MMOS by two-step MR. This study identified potential causal relationships between 11 lipids and MMOS, and 40 metabolites and MMOS, respectively. Phosphatidylethanolamine (18:0_18:2) levels mined from 179 lipids by MR Analysis increased the risk of MMOS (OR: 1.962; 95%CI:1.298,2.964; P=0.001). There is no strong evidence for a relationship between genetically predicted MMOS and phosphatidylethanolamine (18:0_18:2) levels (P=0.628). The proportion of gene predictions for phosphatidylethanolamine (18:0_18:2) levels mediated by 1-stearoyl-(glycosylphosphatidylinositol) GPI (18:0) levels was 12.40%. This study identifies 1-stearoyl-GPI (18:0) levels as a potential mediator that may mediate the causal relationship between phosphatidylethanolamine (18:0_18:2) levels and MMOS, This provides direction for the investigation of MMOS, but further research of other possible potential mediators is still needed.

Efficacy of KarXT on negative symptoms in acute schizophrenia: A post hoc analysis of pooled data from 3 trials

BackgroundCurrently approved antipsychotics do not adequately treat negative symptoms (NS), which are a major determinant of functional disability in schizophrenia. KarXT, an M1 /M4 preferring muscarinic receptor agonist, has shown efficacy as a broad-spectrum monotherapy for the treatment of schizophrenia in participants with acute psychosis. Post hoc analyses evaluated the possibility that NS improve independently of positive symptoms with KarXT in a subgroup of participants with moderate-to-severe NS and no predominance of positive symptoms. MethodsData were pooled from the three pivotal trials of KarXT monotherapy in people with schizophrenia with an acute exacerbation of psychosis. All 3 studies used similar 5-week randomized, double-blind, placebo-controlled designs (modified intention-to-treat sample N = 640). PANSS criteria proposed in the literature identified a subset of study participants (n = 64) with prominent NS. ResultsKarXT was significantly better than placebo on PANSS Marder Negative Factor Scores in the full sample (p < .001; Cohen's d = 0.42) and more so in the prominent NS subgroup (p < .001; Cohen's d = 1.18). Further, the KarXT effect in the NS subgroup remained significant after accounting for changes in positive symptoms, depression/anxiety, disorganization, and hostility. ConclusionsParticipants with prominent NS revealed greater improvement of NS following KarXT therapy than the full sample that persisted after accounting for positive and other symptoms. While these findings must be interpreted with caution, they are consistent with the possibility that NS improvements associated with KarXT are not secondary to improvements in other symptom domains and support further investigation in larger, stable outpatient studies.

Combining cohorts of prospectively collected and linked data to improve health after release from prison

BackgroundWhile people who experience incarceration have remarkably poor health profiles, undertaking research to inform evidence-based responses is complicated by difficulties of recruiting people in prison; high rates of socioeconomic marginalisation, study attrition; and legislative and financial barriers to linked data research. There are many advantages to pooling data from multiple studies involving people who experience incarceration, including greater statistical power and geographic and participant heterogeneity. However, there are also challenges that need to be addressed. MethodsWe combined four prospective cohort studies of adults released from prisons in four Australian states. Pre-release interviews, and validated screening assessments, were linked to primary care, medicine dispensing, hospital, alcohol and other drug treatment services, ambulatory mental health, ambulance, corrective services, and death records. Data were harmonised by team members reviewing variable definitions and categories within subject domains. ResultsThe combined cohort consists of 4,232 adults, including 1,544 Indigenous people and 905 women, with a median age of 31 years. Data linkage will enable a median of 9.3 years of prospective follow-up after release from incarceration. Differences in data structures, coding systems between and within datasets, changes over time, and grouping of records belonging to the same event were also addressed. ConclusionThis combined multi-site cohort study is an example of a complex, policy-oriented data linkage project. It was developed to underpin evidence-based, culturally appropriate interventions, health policy and service development for people who were incarcerated. This presentation will discuss the processes and pitfalls experienced while building a multi-sectoral, multi-jurisdictional data linkage project.

ThP7.1 - The effect of socioeconomic status on outcomes in major trauma: a systematic review and meta-analysis

Abstract Background Major trauma poses a significant public health concern, with survivors often suffering long-term disability. There is growing interest in understanding the complex relationships between socioeconomic deprivation and major trauma in recent years. Anecdotal evidence suggests that social deprivation leads to more violent and debilitating injuries. There remains, however, a paucity in literature evaluating major trauma outcomes in relation to socioeconomic deprivation. Methods A comprehensive search of MEDLINE, EMBASE, and Cochrane databases was performed to identify eligible studies from 1947 to March 2024. The primary outcome is to establish the proportion of patients with the highest socioeconomic deprivation, with secondary outcomes evaluating surgical intervention rates, length of stay, and mortality. Quantitative pooling of data was based on the random effects model. Results Fourteen studies reporting on 878,872 major trauma patients were included. A substantial proportion of major trauma incidents occurred in the most deprived group at 28%. There were more male patients in the most deprived compared to the least deprived group (OR 1.36, 95% CI 1.14-1.63, I2=99%). There were no differences in surgical intervention (OR 1.74, 95% CI 0.97-3.13, I2=0%) and length of stay (WMD 1.15 days, 95% CI -0.32-2.62, I2=82%) regardless of background. Interestingly, mortality was higher in the most deprived group (OR 2.02, 95% CI 1.14-3.57, I2=80%). Conclusion Major trauma is more prevalent in deprived areas. Although rates of surgery and length of stay did not differ, mortality is higher in the most deprived group. The planning of public health interventions should target areas of higher deprivation.

Tracheal Ultrasound for Diagnosis of Tracheal Cartilaginous Sleeve in Patients with Syndromic Craniosynostosis.

The aim of this study was to assess the utility of ultrasound (US) imaging for diagnosis of abnormal tracheal morphology, such as tracheal cartilaginous sleeves (TCS), in patients with syndromic craniosynostosis (SC). Age-matched cohort study. Tertiary pediatric hospital. Two age-matched cohorts were identified: patients with SC and known TCS based upon airway endoscopy and normal controls without tracheal pathology. Enrolled patients underwent awake US of the neck which were randomized and reviewed by blinded pediatric radiologists and rated on presence or absence of normal tracheal cartilage morphology and visualization or nonvisualization of a tracheostomy tube. Fisher's exact test was used to assess pooled data. Fleiss' Kappa (κ) was calculated to assess inter-rater reliability. Ten patients were included in each cohort. Control patients were gender and age-matched to TCS patients with a mean difference of 3.7 months (±3.9 months). Across all raters, cartilage type was correctly identified in 93% (95% confidence interval [CI]: 84%-98%) and tracheostomy visualization in 97% (95% CI: 89%-99%). The sensitivity and specificity for detection of abnormal cartilage pathology was 87% and 100%, respectively. Inter-rater reliability for cartilage assessment was κ = 0.88 (95% CI: 0.67-1.00, P < .05) and 0.83 (95% CI: 0.58-1.00, P < .05) for tracheostomy presence. This study demonstrated that tracheal US is a feasible, accurate screening tool for TCS, and can be successfully performed non-sedated in patients up to 18 years of age, both with and without tracheostomy tubes in place.

Causal relationship between multiple sclerosis and spinal stenosis: Two-sample Mendelian randomization.

To investigate the causal relationship between multiple sclerosis and spinal stenosis using Mendelian randomization (MR). Genetic loci independently associated with multiple sclerosis and spinal stenosis in people of European origin were selected as instrumental variables using pooled data from genome wide association studies (GWAS). Three MR analyses, MR-Egger, Weighted median and inverse variance weighting (IVW), were used to investigate the causal relationship between multiple sclerosis and spinal stenosis. Heterogeneity and multiplicity tests were performed, and sensitivity analyses were performed using the "leave-one-out" method to explore the robustness of the results. The IVW results showed an OR (95% CI) of 1.05 (1.01-1.08), P = .016, indicating a causal relationship between MS and spinal stenosis. And no heterogeneity and multiplicity were found by the test, and sensitivity analysis also showed robust results. In this study, genetic data were analyzed and explored using 2-sample MR analysis, and the results showed a causal relationship between multiple sclerosis and the occurrence of spinal stenosis.

Outcomes of robotic versus laparoscopic-assisted surgery in patients with rectal cancer: a systematic review and meta-analysis.

Robotic-assisted rectal surgery (RARS) and Laparoscopic-assisted rectal surgery are the two techniques that are increasingly used for rectal cancer, and both have their advantages and disadvantages. This meta-analysis will analyze the outcomes of both techniques to determine their relative performance and suitability. An extensive search was carried out on PubMed, Cochrane, Scopus, Embase, and Google Scholar, followed by a meta-analysis of all randomized controlled trials (RCTs) to assess both approaches for rectal cancer. This meta-analysis is comprised of fifteen RCTs. The conversion to open surgery (RR = 0.53, 95% CI: 0.38-0.74, P = 0.0002) was significantly lower in the RARS group. The outcomes like anastomotic leak, postoperative ileus, postoperative urinary retention (POUR), surgical site infection (SSI), and intra-abdominal abscess showed no significant difference between the two groups. The reoperation rate (RR = 0.56, 95% CI: 0.34-0.95, P = 0.03) was lower in the robotic group. High heterogeneity was obtained when pooling data on operative time, length of hospital stay, and blood loss. Oncological outcomes, including local recurrence, the number of harvested lymph nodes (LN) and distal resection margin showed no significant distinction among both groups, while the positive circumferential resection margin (CRM) (RR = 0.67, 95% CI: 0.49-0.91, P = 0.01) was lower in the RARS group. RARS demonstrated a significantly higher rate of total mesorectal excision (TME) (RR = 1.07, 95% CI: 1.01-1.14, P = 0.03). RARS is safe and feasible for rectal cancer patients and may be superior or equivalent to Laparoscopic-assisted rectal surgery, but high-standard, large-scale trials are required to determine the best approach.

Estimating the number of Canadians suffering from fecal incontinence using pooled prevalence data from meta-analysis

Background and aimFecal incontinence (FI) is defined as the unintended loss of solid or liquid stool. FI adversely affects the patient’s quality of life. However, due to stigma, lack of awareness, and underdiagnosis, there is a notable gap in the knowledge regarding its prevalence. This study aimed to conduct a systematic review and meta-analysis of published literature reporting on FI prevalence and estimate the number of people afflicted by FI.MethodsA systematic review was conducted following the PRISMA 2020 guidelines, using the Embase, MEDLINE, CINHAL, and PubMed databases to identify relevant publications in the English language. Two reviewers independently screened the articles and extracted data. The reference sections and content of the review papers were also evaluated. Thirty-two articles were selected and included. A meta-analysis of proportions was performed using RStudio software. A sub-analysis was conducted to account for the variation between sample population age groups to minimize heterogeneity. The pooled prevalence was extrapolated to the Canadian population and a sample of ten densely populated countries to estimate the number of people affected by FI.ResultsThe Mean pooled FI prevalence in men and women was 7% (95% CI: 6-9%) and 10% (95% CI: 8-12%), respectively. The sub-analysis mean pooled prevalence of FI in men and women was 8% (95% CI: 6-10%) and 10% (95% CI: 8-12%), respectively. The authors estimate that between 1 and 1.5 million Canadians and 320 to 500 million people in the ten most populous countries suffer from FI.ConclusionFecal incontinence is a prevalent underdiagnosed condition requiring appropriate and timely treatment to improve a patient’s quality of life.

Adenoma detection rate by colonoscopy in real-world population-based studies: a systematic review and meta-analysis.

Adenoma detection rate (ADR) is a quality indicator set at a minimum of 25% in unselected populations by the European Society of Gastrointestinal Endoscopy (ESGE). Nevertheless, a lack of pooled observational data resembling real-world practice limits support for this threshold. We aimed to perform a systematic review with meta-analysis to evaluate the pooled rates for conventional adenoma detection, polyp detection (PDR), cecal intubation, bowel preparation, and complications in population-based studies. The PubMed, Scopus, and Web of Science databases were searched until May 2023 for populational-based studies reporting overall ADR in unselected individuals. A random-effects model was used for meta-analysis. 31 studies were included, comprising 3 644 561 subjects. A high quality of procedures was noticeable, with a high cecal intubation rate and low complication rate. The overall pooled ADR, PDR, and rate of cancer detection were 26.5% (95%CI 23.3% to 29.7%), 38.3% (95%CI 32.5% to 44.1%), and 2.7% (95%CI 1.5% to 3.9%), respectively. ADR varied according to indication: screening 33.3% (95%CI 24.5% to 42.2%), surveillance 42.9% (95%CI 36.9% to 49.0%), and diagnostic 24.7% (95%CI 19.5% to 29.9%), with subgroup analysis revealing rates of 34.4% (95%CI 22.0% to 40.5%) for post-fecal occult blood test and 26.6% (95%CI 22.6% to 30.5%) for primary colonoscopy screening. Diminutive conventional adenomas yielded a pooled rate of 59.9% (95%CI 43.4% to 76.3%). The pooled rate for overall serrated lesion detection was 12.4% (95%CI 8.8% to 16.0%). Male sex and higher age were significantly associated with an ADR above the benchmark. This first meta-analysis relying on real-world observational studies supports the ESGE benchmark for ADR, while suggesting that different benchmarks might be used according to indication, sex, and age.

Credit Risk Management and Profitability of Nepalese Commercial Banks

Banks are an essential component in the economy in the process of creating economic growth in both developed and developing countries. In order to contribute to its commitment to promote growth, banks should be able to lock in on the stability of their financial performance. This study has examined the relationship of credit risk management on performance of Nepalese commercial banks. The descriptive, Correlational research design and review have been adopted for the study. The pooled data of ten commercial banks out of total population of twenty commercial banks operating up to January 2024 has been analyzed. The findings indicate that specific financial indicators, such as credit to deposit ratio, non-performing loan, and interest spread rate, play crucial roles in influencing ROA and ROE. Major issue on non-performing loan and impairment cost were highlighted. Identified that gross domestic product growth rate has an insignificant positive impact on profitability of commercial banks in Nepal. These insights contribute to a deeper understanding of the dynamics within the banking sector, offering valuable implications for stakeholders and policymakers.

Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology

Obesity is associated with numerous psychosocial complications, making psychiatric safety a consideration for treating people with obesity. Few studies have investigated the psychiatric safety of newly available antiobesity medications. To evaluate the psychiatric safety of subcutaneous semaglutide, 2.4 mg, once weekly in people without known major psychopathology. This post hoc analysis of pooled data from the randomized, double-blind, placebo-controlled, multicenter phase 3a STEP 1, 2, and 3 trials (68 weeks; 2018-2020) and phase 3b STEP 5 trial (104 weeks; 2018-2021) included adults with overweight or obesity; STEP 2 participants also had type 2 diabetes. Trial designs have been published previously. Semaglutide, 2.4 mg, vs placebo. Depressive symptoms and suicidal ideation/behavior were assessed using the Patient Health Questionnaire (PHQ-9) and Columbia-Suicide Severity Rating Scale, respectively. Psychiatric and nervous system disorder adverse events were investigated. This analysis included 3377 participants in the STEP 1, 2, and 3 trials (2360 women [69.6%]; mean [SD] age, 49 [13] years) and 304 participants in STEP 5 (236 women [77.6%]; mean [SD] age, 47 [11] years). In the STEP 1, 2, and 3 trials, mean (SD) baseline PHQ-9 scores for the semaglutide, 2.4 mg, and placebo groups were 2.0 (2.3) and 1.8 (2.3), respectively, indicating no/minimal symptoms of depression. PHQ-9 scores at week 68 were 2.0 (2.9) and 2.4 (3.3), respectively; the estimated treatment difference (95% CI) between groups was -0.56 (-0.81 to -0.32) (P < .001). Participants treated with semaglutide vs placebo were less likely to shift (from baseline to week 68) to a more severe category of PHQ-9 depression (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001). Based on the Columbia-Suicide Severity Rating Scale, 1% or fewer of participants reported suicidal ideation/behavior during treatment, with no differences between semaglutide, 2.4 mg, and placebo. Psychiatric disorder adverse events were generally balanced between groups. Similar results were observed in STEP 5. The results of this post hoc analysis suggest that treatment with semaglutide, 2.4 mg, did not increase the risk of developing symptoms of depression or suicidal ideation/behavior vs placebo and was associated with a small but statistically significant reduction in depressive symptoms (not considered clinically meaningful). People with obesity should be monitored for mental health concerns so they can receive appropriate support and care. ClinicalTrials.gov Identifiers: STEP 1 (NCT03548935), 2 (NCT03552757), 3 (NCT03611582), and 5 (NCT03693430).

Prevalence of mental illness among Australian and New Zealand people in prison: A systematic review and meta-analysis of studies published over five decades.

The higher rate of mental illness, including severe psychotic disorders, among people in prisons compared to the general community is well-established. However, there have been no reviews or attempts to pool data on the reported prevalence of mental illness across prisons in Australia and New Zealand. A systematic search of electronic databases from 1966 to the end of 2020 was conducted to identify studies reporting rates of 'any' mental illness, and separately rates of psychotic illness, among adult men and women in Australian and New Zealand prisons. A meta-analysis was performed according to PRISMA guidelines (PROSPERO ID: CRD42021241946), with separate analyses conducted for lifetime and current prevalence rates. Seventeen studies, with a total of 10,209 people in prison, met inclusion criteria. The pooled lifetime prevalence of 'any' mental illness was 69.0% (95% confidence interval = [0.56, 0.79]), and the pooled lifetime prevalence for psychosis was 9.1% (95% confidence interval = [0.07, 0.12]). Meanwhile, the pooled prevalence for 'any' current mental illness was 54.0% (95% confidence interval = [0.39, 0.68]) and for any current psychosis was 6.4% (95% confidence interval = [0.04, 0.10]). There was substantial heterogeneity between studies, with evidence that lifetime rates of psychosis have increased over time, with true prevalence estimates in 95% of all comparable populations falling between 2.7% and 26.4%. The prevalence of mental illness, including severe psychotic illness, is high in Australian and New Zealand prisons. Furthermore, there is evidence that the prevalence of psychosis may be increasing over time, indicating more effort is needed to ensure diversion of people with mental illness away from the criminal justice system and into healthcare pathways.

AMTransformer: A Koopman theory-based transformer for learning additive manufacturing dynamics in laser processes

Recent advancements in machine learning (ML) have shown unprecedented promise in understanding and predicting additive manufacturing (AM) dynamics. However, existing ML studies on AM often lack a comprehensive approach to address the multi-scale complexities inherent in AM processes and tend to employ context-specific methods. To address these limitations, we present a foundational method for formulating AM dynamics suitable for ML modeling. We then introduce a novel approach, the AMTransformer, designed to comprehend complex spatiotemporal dynamical dependencies among physical entities and their properties within the AM process. To enhance the understanding of AM dynamics, our method adapts Koopman&amp;rsquo;s theory to generate latent embeddings of AM states and their transitions, effectively extracting hidden features related to physical properties and dynamical dependencies. In addition, by utilizing the transformer&amp;rsquo;s attention mechanism, the proposed approach enhances the learning of non-local, non-linear dynamical dependencies across multiple scales. Our experiments, conducted using melt pool data from a laser powder bed fusion process, demonstrate that the AMTransformer outperforms traditional transformer and convolutional long short-term memory models. Specifically, the AMTransformer achieved structural similarity, mean absolute error, and accuracy metric values of 0.9206, 0.0009 mm2, and 92.73%, respectively. These results indicate the AMTransformer&amp;rsquo;s superior ability to predict future AM states, attributed to its improved learning of complex AM dynamics. By combining linear Koopman-based methods with non-linear transformer-based approaches, the AMTransformer significantly improves data-driven modeling for AM, providing a more comprehensive understanding of AM dynamics. Furthermore, the generalizability of the proposed method facilitates the expansion of the model&amp;rsquo;s scope and enhances its applicability across various fields.

Trends and risk indicators for high fertility among Nigerian female youth aged 15–29 years: A pooled data analysis

IntroductionNigeria's age-specific fertility rates are highest among the country's youth population, yet little is known about the factors that influence female youth fertility in Nigeria. This study examined fertility trends and risk factors associated with high fertility among Nigerian female youth aged 15 to 29. MethodsWe examined a pooled data from four rounds of the Nigeria Demographic and Health Surveys (conducted in 2003, 2008, 2013, and 2018). Of the data, 62,713 female youth were extracted for this study. Descriptive statistics and multinomial logistic regression were employed. ResultsThe results show that 21.5 % of the sample had 3 or more children. Between 2003 and 2018, there was a drop of only 28 live births per 1000 women among the youth. Female youth with less than a secondary education were twice as likely to have 1–2 children (adjusted odds ratio [aOR] = 1.54, 95 % confidence interval [CI] = 1.43–1.66) and three times as likely to have 3 or more children (aOR = 3.32, 95 % CI = 3.03–3.64) compared to those with a secondary education or higher. Unmarried female youth were 95 % less likely to have 1–2 children and 98 % less likely to have 3 or more children. Additionally, female youth from the lowest-income families were twice as likely to have 1–2 children (aOR = 2.06, 95 % CI = 1.84–1.84) and four times as likely to have 3 or more children (aOR = 3.50, 95 % CI = 3.03–4.05) compared to those from the highest-income families. ConclusionTo control high fertility, significant improvement in education, employment, ending early marriage, poverty and unfavorable pronatalist cultural norms, are required.

Evaluation of risk prediction models to select lung cancer screening participants in Europe: a prospective cohort consortium analysis

Lung cancer risk prediction models might efficiently identify individuals who should be offered lung cancer screening. However, their performance has not been comprehensively evaluated in Europe. We aimed to externally validate and evaluate the performance of several risk prediction models that predict lung cancer incidence or mortality in prospective European cohorts. We analysed 240 137 participants aged 45-80 years with a current or former smoking history from nine European countries in four prospective cohorts from the pooled database of the Lung Cancer Cohort Consortium: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (Finland), the Nord-Trøndelag Health Study (Norway), CONSTANCES (France), and the European Prospective Investigation into Cancer and Nutrition (Denmark, Germany, Italy, Spain, Sweden, the Netherlands, and Norway). We evaluated ten lung cancer risk models, which comprised the Bach, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 model (PLCOm2012), the Lung Cancer Risk Assessment Tool (LCRAT), the Lung Cancer Death Risk Assessment Tool (LCDRAT), the Nord-Trøndelag Health Study (HUNT), the Optimized Early Warning Model for Lung Cancer Risk (OWL), the University College London-Death (UCLD), the University College London-Incidence (UCLI), the Liverpool Lung Project version 2 (LLP version 2), and the Liverpool Lung Project version 3 (LLP version 3) models. We quantified model calibration as the ratio of expected to observed cases or deaths and discrimination using the area under the receiver operating characteristic curve (AUC). For each model, we also identified risk thresholds that would screen the same number of individuals as each of the US Preventive Services Task Force 2021 (USPSTF-2021), the US Preventive Services Task Force 2013 (USPSTF-2013), and the Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) criteria. Among the participants, 1734 lung cancer cases and 1072 lung cancer deaths occurred within five years of enrolment. Most models had reasonable calibration in most countries, although the LLP version 2 overpredicted risk by more than 50% in eight countries (expected to observed ≥1·50). The PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI models showed similar discrimination in most countries, with AUCs ranging from 0·68 (95% CI 0·59-0·77) to 0·83 (0·78-0·89), whereas the LLP version 2 and LLP version 3 showed lower discrimination, with AUCs ranging from 0·64 (95% CI 0·57-0·72) to 0·78 (0·74-0·83). When pooling data from all countries (but excluding the HUNT cohort), 33·9% (73 313 of 216 387) of individuals were eligible by USPSTF-2021 criteria, which included 74·8% (1185) of lung cancers and 76·3% (730) of lung cancer deaths occurring over 5 years. Fewer individuals were selected by USPSTF-2013 and NELSON criteria. After applying thresholds to select a population of equal size to USPSTF-2021, the PLCOm2012, LCDRAT, LCRAT, Bach, HUNT, OWL, UCLD, and UCLI, models identified 77·6%-79·1% of future cases, although they selected slightly older individuals compared with USPSTF-2021 criteria. Results were similar for USPSTF-2013 and NELSON. Several lung cancer risk prediction models showed good performance in European countries and might improve the efficiency of lung cancer screening if used in place of categorical eligibility criteria. US National Cancer Institute, l'Institut National du Cancer, Cancer Research UK.

Efficacy and Safety of Sphingosine 1-Phosphate Receptor Modulators for Ulcerative Colitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Sphingosine 1-phosphate receptor modulators (S1PRMs) are an effective treatment for ulcerative colitis (UC). This review summarizes all available randomized trial data on the efficacy and safety of S1PRM therapy. Multiple publication databases were systematically searched for randomized control trials (RCTs) of adults with moderate to severe UC treated with S1PRMs. Random effects meta-analysis was performed. The risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool, and the overall quality of evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We identified 7 RCTs (1737 patients) involving the use of S1PRMs for moderate to severe UC. During induction, S1PRM therapy was efficacious when compared with placebo for clinical remission [RR: 2.65 (95% CI: 2.00, 3.53)], clinical response [RR: 1.68 (95% CI: 1.48, 1.91)], endoscopic improvement [RR: 2.17 (95% CI: 1.76, 2.68)], endoscopic normalization [RR: 2.56 (95% CI: 1.58, 3.83)], mucosal healing [RR: 2.88 (95% CI: 1.94, 4.26)], and histologic remission [RR: 2.42 (95% CI: 1.60, 3.66)]. Similar results were seen throughout the maintenance peroid, although fewer data were available to pool; notably, both sustained [RR: 3.57 (95% CI: 1.23, 10.35)] and steroid-free [RR: 2.92 (95% CI: 1.35, 6.33)] remission were significantly increased by S1PRM. There were no significant differences in adverse events [RR: 1.02 (95% CI: 0.90, 1.15)] and infections [RR: 1.15 (95% CI: 0.82, 1.60)] between S1PRM and placebo. Pooling of RCT data confirms that S1PRM therapy is both effective and safe for patients with moderate to severe UC.

Impact of Intraoperative Dexamethasone on Perioperative Blood Glucose Levels: Systematic Review and Meta-Analysis of Randomized Trials.

Dexamethasone is associated with increased blood glucose levels that could impact patient outcomes or management. This study aimed to synthesize the available evidence regarding the impact of an intraoperative single dose of dexamethasone on blood glucose levels. We searched CENTRAL, MEDLINE, and clinicaltrials.gov for randomized controlled trials (RCTs) comparing a single intraoperative dose of dexamethasone to control in adult patients who underwent noncardiac surgery. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the review was registered in PROSPERO (CRD42023420562). Data were pooled using a random-effects model. We reported pooled dichotomous data using odds ratios (OR) and continuous data using the mean difference (MD), reporting 95% confidence intervals (95% CIs), and corresponding P-values for both. Confidence in the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. As primary outcomes we assessed maximum blood glucose levels measurement and variation from baseline within 24 hours of surgery; blood glucose levels measurement and variation from baseline at 2, 4, 8, 12, and 24 hours after dexamethasone administration. As secondary outcomes, we evaluated insulin requirements and hyperglycemic events. We included 23 RCTs, enrolling 11,154 participants overall. Dexamethasone was associated with a significant increment in blood glucose levels compared to control at all timepoints. The results showed an increase compared to control of 0.37 mmol L-1 (6.7 mg dL-1) at 2 hours (95% CI, 0.16-0.58 mmol L-1 or 2.9-10.5 mg dL-1), 0.97 mmol L-1 (17.5 mg dL-1) at 4 hours (95% CI, 0.67-1.25 mmol L-1 or 12.1-22.5 mg dL-1), 0.96 mmol L-1 (17.3 mg dL-1) at 8 hours (95% CI, 0.55-1.36 mmol L-1 or 9.9-24.5 mg dL-1), 0.90 mmol L-1 (16.2 mg dL-1) at 12 hours (95% CI, 0.62-1.19 mmol L-1 or 11.2-21.4 mg dL-1) and 0.59 mmol L-1 (10.6 mg dL-1) at 24 hours (95% CI, 0.22-0.96 mmol L-1 or 4.0-17.3 mg dL-1). No difference was found between subgroups regarding diabetic status (patients with diabetes versus patients without diabetes) in all the outcomes except 2 (maximum blood glucose levels variation within 24 hours and variation at 4 hours) and dexamethasone dose (4-5 mg vs 8-10 mg) in all the outcomes except 2 (blood glucose levels at 24 hours and hyperglycemic events). Mean blood glucose levels rise between 0.37 and 1.63 mmol L-1 (6.7 and 29.4 mg dL-1) within 24 hours after a single dose of dexamethasone administered at induction of anesthesia compared to control, but in most patients this difference will not be clinically relevant.

49169 Impact of secukinumab on high-sensitivity C-reactive protein and erythrocyte sedimentation rate: Post hoc analysis of pooled data from the SUNSHINE and SUNRISE Phase 3 randomized trials

49169 Impact of secukinumab on high-sensitivity C-reactive protein and erythrocyte sedimentation rate: Post hoc analysis of pooled data from the SUNSHINE and SUNRISE Phase 3 randomized trials