Low-risk Population Research Articles

Dynamic and concordance-assisted learning for risk stratification with application to Alzheimer's disease.

Dynamic prediction models capable of retaining accuracy by evolving over time could play a significant role for monitoring disease progression in clinical practice. In biomedical studies with long-term follow up, participants are often monitored through periodic clinical visits with repeat measurements until an occurrence of the event of interest (e.g. disease onset) or the study end. Acknowledging the dynamic nature of disease risk and clinical information contained in the longitudinal markers, we propose an innovative concordance-assisted learning algorithm to derive a real-time risk stratification score. The proposed approach bypasses the need to fit regression models, such as joint models of the longitudinal markers and time-to-event outcome, and hence enjoys the desirable property of model robustness. Simulation studies confirmed that the proposed method has satisfactory performance in dynamically monitoring the risk of developing disease and differentiating high-risk and low-risk population over time. We apply the proposed method to the Alzheimer's Disease Neuroimaging Initiative data and develop a dynamic risk score of Alzheimer's Disease for patients with mild cognitive impairment using multiple longitudinal markers and baseline prognostic factors.

Systematic Review of Clinical Prediction Models for the Risk of Emergency Caesarean Births.

Globally, caesarean births (CB), including emergency caesareans births (EmCB), are rising. It is estimated that nearly a third of all births will be CB by 2030. Identify and summarise the results from studies developing and validating prognostic multivariable models predicting the risk of EmCBs. Ultimately understanding the accuracy of their development, and whether they are operationalised for use in routine clinical practice. Studies were identified using databases: MEDLINE, CINAHL, Cochrane Central and Scopus with a search strategy tailored to models predicting EmCBs. Prospective studies developing and validating clinical prediction models, with two or more covariates, to predict risk of EmCB. Data were extracted onto a proforma using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). In total, 8083 studies resulted in 56 unique prediction modelling studies and seven validating studies, with a total of 121 different predictors. Frequently occurring predictors included maternal height, maternal age, parity, BMI and gestational age. PROBAST highlighted 33 studies with low overall bias, and these all internally validated their model. Thirteen studies externally validated; only eight of these were graded an overall low risk of bias. Six models offered applications that could be readily used, but only one provided enough time to offer a planned caesarean birth (pCB). These well-refined models have not been recalibrated since development. Only one model, developed in a relatively low-risk population, with data collected a decade ago, remains useful at 36 weeks for arranging a pCB. To improve personalised clinical conversations, there is a pressing need for a model that accurately predicts the timely risk of an EmCB for women across diverse clinical backgrounds. PROSPERO registration number: CRD42023384439.

COVID-19 policy responses, social norms, and behavior change in MENA

ABSTRACT Inducing behavior change is a missing factor in the face of viral threats. We provide evidence from a natural experiment in 2020 on the effects of containment, closure, and economic policy responses to COVID-19 on change in human mobility behavior in the Middle East and North Africa (MENA) region and worldwide. We also examine how social norms, namely risk taking and patience, and institutional trust, could explain the heterogenous effects of policy responses on behavior change. Our results show that the stringency of containment and closure policies decreased human mobility in MENA and worldwide. Risk-averse populations and populations with low-time preference were more likely to pre act and lower their mobility independent of containment and closure policies. The effectiveness of risk communication in promoting positive mobility change increased by the level of institutional trust. Specifically in MENA, populations were less responsive to the actual disease risk and the public perception of that risk. Familiarity with COVID-19 induced negative behavior change among impatient populations. Economic support policies promoted strong positive mobility change among low-risk and high-time preference populations. Income support seems to be the effective economic policy response in low-income countries and debt relief the effective one in higher-income countries.

Valvular and perivalvular thrombosis following self-expandable aortic valve replacement: analysis of 100 multi-detector computed tomography scans

Abstract Aims Subclinical thrombosis may represent an early stage of prosthesis structural disease. Most of the available evidence on the incidence, location, predictors, and consequences of thrombosis comes from studies that have employed balloon-expandable valves. We aimed to describe the different localisations of valvular and perivalvular thrombosis and analyse prosthesis-host multi-detector computed tomography predictors in the context of self-expandable prosthesis. Additionally, we aimed to assess the impact of valvular and perivalvular thrombosis on prosthesis performance and subsequent clinical outcomes. Methods and results This analysis includes 100 consecutive patients with normal renal function who underwent transcatheter aortic valve replacement using Evolut R and received multi-detector computed tomography and transthoracic bi-dimensional echocardiography at the 6 month follow-up. Leaflet thrombosis was detected in 18 (18%) patients; 6 (6%) had at least one leaflet with severe thrombosis. Thrombosis of the anatomic sinus was detected in 24 patients (24%) and was more prevalent in the non-coronary sinus. Subvalvular thrombosis with partial or complete circumferential involvement of the prosthesis inner skirt was diagnosed in 23 patients (23%). Bicuspid valve was the predictor with highest association with hypoattenuated lesions [least absolute shrinkage and selection operator coefficient 0.35, 95%, confidence interval (CI) 0.21–0.68]. There was no difference in terms of haemodynamic structural valve dysfunction, neurological events, and re-hospitalisation between the groups with and without thrombosis (hazard ratio: 0.86, 95% CI: 0.24–3.06, P = 0.82). Conclusion This study showed that in a relatively low-risk population, valvular and perivalvular thrombosis were not rare phenomena following transcatheter aortic valve replacement at early follow-up. Bicuspid valve showed the strongest association with post-implant thrombosis.

Epidemiology of Hepatitis C over 28 years of monitoring Canadian blood donors: Insight into a low-risk undiagnosed population

BackgroundHepatitis C is a blood-borne infection with the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% (50–80%) of infections become chronic and exhibit anti-HCV and HCV nucleic acid (NAT) positivity. Direct acting oral pan genotypic antiviral treatment became available in 2014 and was free for most Canadians in 2018. Clinical screening for HCV infection is risk-based. About 1% of Canadians have been infected with HCV, with 0.5% chronically infected (about 25% unaware) disproportionately impacting marginalized groups. Blood donors are in good health, are deferred for risks such as injection drug use and can provide insight into the low-risk undiagnosed population. Here we describe HCV epidemiology in first-time blood donors over 28 years of monitoring.MethodsAll first-time blood donors in all Canadian provinces except Quebec (1993 to 2021) were analyzed. All blood donations were tested for HCV antibodies (anti-HCV) and since late 1999 also HCV NAT. A case-control study was also included. All HCV positive donors (cases) since 2005 and HCV negative donors (1:4 ratio controls) matched for age, sex and location were invited to complete a risk factor interview. Separate logistic regression models for anti-HCV positivity and chronic HCV assessed the association between age cohort, sex, region and neighbourhood material deprivation and ethnocultural concentration. Case: control data were analysed by logistic regression.ResultsThere were 2,334,238 donors from 1993 to 2021 included. Prevalence for anti-HCV was 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021 (p < 0.0001). In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar, for chronic HCV were male sex (OR 1.8, 1.6,2.1), birth between 1945 and 1975 (OR 7.1, 5.9,8.5), living in the western provinces (OR 1.4, 1.2,1.7) and living in material deprived (OR 2.7, 2.1,3.5) and more ethnocultural concentrated neighbourhoods (OR 1.8, 1.3,2.5). There were 318 (35.4%) of chronic HCV positive and 1272 (39.6%) of controls who participated in case control interviews. The strongest risks for acquisition were injection drug use (OR 96.9, 22.3,420.3) and birth in a high prevalence country (OR 24.5, 11.2,53.6).ConclusionsBlood donors have 16 times lower HCV prevalence then the general population. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risks for acquisition missed by risk-based patient screening.

Use of routinely collected blood donation data for expanded HIV and Syphilis surveillance in Blantyre district, Malawi.

The World Health Organization recommends that all blood donations be screened for transfusion transmissible infections; these data are currently not incorporated into national disease surveillance efforts. We set out to use routinely collected data from blood donors in Blantyre district, Malawi to explore HIV and syphilis prevalence and identify sero-conversions among repeat donors. We conducted a retrospective cohort analysis of blood donation data collected by the Malawi Blood Transfusion Service from 2015 to 2021. All blood donations were routinely screened for HIV and syphilis. We characterized donor demographics as well as screening outcomes, including identifying sero-conversions among repeat donors who previously tested negative on their last donation. A total of 23,280 donations from 5,051 donors were recorded, with a median frequency of donations of 3 (IQR:2-6). Most donors were male (4,294; 85%) and students (3,262; 64.6%). Prevalence of HIV at first donation was 1.0% (52/5,051) and prevalence of syphilis was 1.6% (80/5,051); 52 HIV sero-conversions and 126 syphilis sero-conversions were identified, indicating an incidence rate per 1,000 person-years of 5.9 (95% CI: 4.7, 7.4) and 13.3 (95% CI:11.4, 15.4) respectively. Students had a lower prevalence of HIV and syphilis but higher risk of syphilis seroconversion. While blood donors are generally considered a low-risk population for HIV and syphilis, we were able to identify relatively high rates of undiagnosed HIV and syphilis infections among donors. Routinely collected data from national blood donation services may be used to better understand local HIV and syphilis epidemiology, with the potential to enhance disease surveillance systems. These findings may be used to identify priority prevention areas and populations in Blantyre district that can inform targeted interventions for improved disease prevention, testing and treatment.

Maternal negative affect in pregnancy predicts cytokine levels which in turn predict birth outcomes – A prospective longitudinal study in a low-risk population

BackgroundStress and negative mood in pregnancy have been linked to less favorable birth outcomes, but the mechanisms underlying this effect remain largely unknown. We examined associations between emotions in pregnancy, pro- and anti-inflammatory cytokines (IFN-γ, IL-6, IL-8, IL-10, IL-12, IL-17, MCP-1, MIP-1β, TNF-α) and birth outcomes (gestational age at birth and birth weight) in a low-risk sample. MethodsAt each trimester of pregnancy, participants (N = 74) completed the Positive and Negative Affect Schedule, Perceived Stress Scale, Edinburgh Postnatal Depression Scale, and State-Trait Anxiety Inventory. They provided blood samples in the third trimester. Multivariate regression with a reduction of dimensionality (orthogonal projection to latent structures) was used to assess associations between maternal emotions, cytokine levels, and birth outcomes. ResultsWe found significant positive associations between negative mood (depressive symptoms in the second and third trimesters and negative affect in the third trimester) and anti-inflammatory cytokine IL-10 levels, and negative associations between maternal distress in the second and third trimesters and pro-/anti-inflammatory cytokine ratios (IFN-γ/IL-10, TNF-α/IL-10 and IL-6/IL-10). Higher levels of pro-inflammatory cytokines IFN-γ, IL-12, IL-17, and TNF-α were associated with younger gestational age at birth and lower birth weight. LimitationsWe did not control for relevant factors such as social support, health-related behaviors, or cortisol levels. ConclusionsNegative mood in mid- and late pregnancy may shift cytokine balance toward the anti-inflammatory cytokine dominance. Our results provide further evidence for the negative association between pro-inflammatory cytokines in late pregnancy and gestational age at birth/birth weight, which we observed even in a low-risk population.

Validation of ADNEX and IOTA two-step strategy and estimation of risk of complications during follow-up of adnexal masses in low-risk population.

To evaluate the ability of the Assessment of Different NEoplasias in the adneXa (ADNEX) model and the International Ovarian Tumour Analysis (IOTA) two-step strategy to predict malignancy in adnexal masses detected in an outpatient low-risk setting, and to estimate the risk of complications in masses with benign ultrasound morphology managed using clinical and ultrasound follow-up. This single-center study was performed at Hospital Universitari Dexeus, Barcelona, Spain, using interim data from the ongoing prospective observational IOTA Phase-5 (IOTA5) study. The primary aim of the IOTA5 study is to describe the cumulative incidence of complications during follow-up of adnexal masses classified as benign on ultrasound examination. Consecutive patients with an adnexal mass detected between June 2012 and September 2016 in a private center offering screening for gynecological cancer were included and followed up until February 2020. Tumors were classified as benign or malignant based on histology (if patients underwent surgery) or the outcome of clinical and ultrasound follow-up at 12 (range, 10-14) months. Multiple imputation was used when outcomes were uncertain. The ability of the ADNEX model without CA125 and of the IOTA two-step strategy to distinguish benign from malignant masses was evaluated retrospectively using the prospectively collected data. We assessed performance with regard to discrimination (area under the receiver-operating-characteristics curve (AUC)), calibration, classification (sensitivity and specificity) and clinical utility (Net Benefit). In the group of patients with a mass judged to be benign who were selected for conservative management, we evaluated the occurrence of spontaneous resolution or any mass complication during the first 5 years of follow-up by assessing the cumulative incidence of malignancy, torsion, cyst rupture and minor mass complications (inflammation, infection or adhesions) and the time to occurrence of an event. A total of 2654 patients were recruited to the study. After application of exclusion criteria, 2039 patients with a newly detected mass were included for the model validation. Of those, 1684 (83%) masses were benign, 49 (2%) masses were malignant and, for 306 (15%) masses, the outcome was uncertain and therefore imputed. The AUC was 0.95 (95% CI, 0.89-0.98) for ADNEX without CA125 and 0.94 (95% CI, 0.88-0.97) for the two-step strategy. Calibration performance could not be meaningfully interpreted because the small number of malignancies resulted in very wide confidence intervals. The two-step strategy had better clinical utility than did the ADNEX model at malignancy risk thresholds < 3%. There were 1472 (72%) patients whose mass was judged to be benign based on pattern recognition by an experienced ultrasound examiner and were managed with clinical and ultrasound follow-up. In this group, the 5-year cumulative incidence was 66% (95% CI, 63-69%) for spontaneous resolution of the mass, 0% (95% CI, 0-0.2%) for torsion, 0.1% (95% CI, < 0.1-0.4%) for cyst rupture, 0.2% (95% CI, 0.1-0.6%) for a borderline tumor and 0.2% (95% CI, 0.1-0.6%) for invasive malignancy. The ADNEX model and IOTA two-step strategy performed well to distinguish benign from malignant adnexal masses detected in a low-risk population. Conservative management is safe for masses with a benign ultrasound appearance in this population. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Predictive validity of the Standardized Infant NeuroDevelopmental Assessment (SINDA) to identify 4–5 year-old children at risk of developmental delay in a low-risk sample

BackgroundEarly detection of developmental problems is important as it allows for early intervention. Previous studies, in high-risk infants, found high predictive values of atypical scores on the Standardized Infant NeuroDevelopmental Assessment (SINDA) for later neurodevelopmental disorders (i.e., cerebral palsy, intellectual disability). AimsThe present study explored SINDA's predictive values to identify risk of developmental delay at 4–5 years. Study designCohort study. Subjects786 low-risk Dutch children (367 boys; median gestational age: 40 (27–42) weeks; mean birth weight: 3455 (SD 577) grams). Outcome measuresThe SINDA was assessed at 2–12 months and risk of developmental delay was assessed using the Ages and Stages Questionnaire (ASQ) at 4–5 years. SINDA's predictive values were determined for five ASQ domains and the total ASQ score for children at risk of marked (all ASQ domains deviant) and any (one or more ASQ domains deviant) developmental delay. ResultsPresence of one atypical SINDA scale score showed low to moderate sensitivities (12–88 %, depending on the SINDA scale and ASQ domain involved), moderate to high specificities (66–94 %), low positive predictive values (PPVs; 3–16 %), and high negative predictive values (NPVs; 95–100 %) for children at risk of marked and any developmental. Presence of multiple atypical SINDA scale scores predicted deviant ASQ domains slightly better (sensitivities = 11–62 %, specificities = 90–98 %, PPVs = 6–30 %, and NPVs = 95–100 %). ConclusionsIn low-risk infants, SINDA's predictive value is low for detecting children at risk of marked and any developmental delay at 4–5 years, as reflected by the low sensitivities. One of the explanations is the relatively low prevalence of developmental delay in low-risk populations. This might have consequences for the application of the SINDA in general healthcare settings (e.g. child health clinics), but further studies are needed to draw this conclusion.

Soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks’ gestation: association with spontaneous onset of labor and intrapartum fetal compromise in low-risk pregnancies

Previous evidence showed that placental dysfunction triggers spontaneous preterm or term births and intrapartum fetal compromise and often requires urgent delivery, thereby exposing both the fetus and the mother to significant risks. Predicting spontaneous labor onset and intrapartum fetal compromise could improve obstetrical management and outcomes, but this is currently difficult, particularly in low-risk populations. The objective of this study was to examine whether placental dysfunction, as assessed at 36 weeks' gestation by the soluble fms-like tyrosine kinase-1 to placental growth factor ratio, is associated with the interval to spontaneous onset of labor and intrapartum fetal compromise that requires cesarean delivery in a routinely examined population. This was a retrospective analysis of prospectively collected data of women with singleton pregnancies who underwent routine assessment at 35+0 to 36+6 weeks' gestation at the King's College Hospital (London, England). Using a general linear model, the study examined the outcomes related to the soluble fms-like tyrosine kinase-1/placental growth factor ratio, including the time interval from testing to spontaneous onset of labor and the subsequent rate of fetal compromise that required a cesarean delivery. Patients who underwent induction of labor or prelabor cesarean deliveries were excluded from the study. Competing risks regression and Cox regression models were used to estimate the cumulative incidence and the risk of the outcomes of interest. In the screened population of 45,375 patients, 23,831 (52.5%) had spontaneous onset of labor and were included in the analysis. Cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 delivered about 1 week earlier than those with a ratio of ≤50 (39.2 vs 40.0 weeks' gestation; P<.001). The general linear model showed that a larger soluble fms-like tyrosine kinase-1/placental growth factor ratio was associated with earlier spontaneous onset of labor (P<.001), particularly among multiparous women. The soluble fms-like tyrosine kinase-1/placental growth factor ratio was significantly associated, as expected, with cases of preeclampsia and advanced maternal age. The cumulative incidence of spontaneous onset of labor was significantly higher in cases with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 than in those with a ratio 50 (P<.001). Cox regression showed that the risk for spontaneous onset of labor increased with an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 (hazard ratio, 1.424; 95% confidence interval, 1.253-1.618; P<.001) and, as expected, the risk was mitigated over time from when the soluble fms-like tyrosine kinase-1/placental growth factor ratio was measured to spontaneous labor onset (P<.001). Cases with intrapartum fetal compromise had a higher mean soluble fms-like tyrosine kinase-1/placental growth factor ratio than those without intrapartum fetal compromise (21.79 vs 17.67; P<.001). Qualitative addition of fetal compromise to the general linear model showed a higher soluble fms-like tyrosine kinase-1/placental growth factor ratio in cases with fetal compromise than in those without fetal compromise (P=.014). Competing risks regression showed a positive dose-response effect for fetal compromise with increasing soluble fms-like tyrosine kinase-1/placental growth factor ratios (P<.001). Above and below the optimal cutoff of 50, the quoted cumulative incidences were 6.7% and 4.7%, respectively (P<.001). The effect of the soluble fms-like tyrosine kinase-1/placental growth factor ratio remained significant even after adjusting for preeclampsia, which is a well-known major risk factor for fetal compromise. Finally, the proportion of cases with intrapartum fetal compromise who had an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 decreased from 35% to 0% with advancing gestation. This study showed that an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio at 36 weeks' gestation is associated with an earlier gestational age at spontaneous onset of labor and higher rates of intrapartum fetal compromise. There are 2 major implications, namely an soluble fms-like tyrosine kinase-1/placental growth factor ratio >50 indicates imminent labor onset with about a 40% mean risk increase and immediate clinical translation for term pregnancy monitoring. In addition, an increased soluble fms-like tyrosine kinase-1/placental growth factor ratio increases the risk for intrapartum fetal compromise, although outcome variability indicates reassessment within multimarker models.

Bioinformatics analysis and identification of cuproptosis-related long non-coding RNAs in colorectal cancer.

Identifying precise biomarkers for colorectal cancer (CRC) detection and management remains challenging. Here, we developed an innovative prognostic model for CRC using cuproptosis-related long non-coding RNAs (lncRNAs). In this retrospective study, CRC patient transcriptomic and clinical data were sourced from The Cancer Genome Atlas database. Cuproptosis-related lncRNAs were identified and used to develop a prognostic model, which helped categorize patients into high- and low-risk groups. The model was validated through survival analysis, risk curves, independent prognostic analysis, receiver operating characteristic curve analysis, decision curves, and nomograms. In addition, we performed various immune-related analyses. LncRNA expression levels were examined in normal human colorectal epithelial cells (FHC) and CRC cells (HCT-116) using quantitative polymerase chain reaction (qPCR). Six cuproptosis-related lncRNAs were identified: ZKSCAN2-DT, AL161729.4, AC016394.1, AC007128.2, AL137782.1, and AC099850.3. The prognostic model distinguished between high-/low-risk populations, demonstrating excellent predictive ability for survival outcomes. Immunocorrelation analysis showed significant differences in immune cell infiltration and functions, immune checkpoint expression, and m6A methylation-related genes. The qPCR results showed significant upregulation of ZKSCAN2-DT, AL161729.4, AC016394.1, AC007128.2 in HCT-116 cells, while AL137782.1 and AC099850.3 expression patterns were significantly downregulated. Cuproptosis-related lncRNAs can potentially serve as reliable diagnostic and prognostic biomarkers for CRC.

Unisex and Sex-Specific Prescriptive Fetal Growth Charts for Improved Detection of Small-for-Gestational-Age Babies in a Low-Risk Population: A post hoc Analysis of a Cluster-Randomized Study.

Our aim was to develop and evaluate the performance of population-based sex-specific and unisex prescriptive fetal abdominal circumference growth charts in predicting small-for-gestational-age (SGA) birthweight, severe SGA (sSGA) birthweight, and severe adverse perinatal outcomes (SAPO) in a low-risk population. This is a post hoc analysis of the Dutch nationwide cluster-randomized IRIS study, encompassing ultrasound data of 7,704 low-risk women. IRIS prescriptive unisex and IRIS sex-specific abdominal circumference (AC) fetal growth charts were derived using quantile regression. As a comparison, we used the descriptive unisex Verburg chart, which is commonly applied in the Netherlands. Diagnostic parameters were calculated based on the 34-36 weeks' ultrasound. Sensitivity rates for predicting SGA and sSGA birthweights were more than twofold higher based on the IRIS prescriptive sex-specific (respectively SGA 43%; sSGA 59%) and unisex (SGA 39%; sSGA 55%) charts, compared to the Verburg chart (SGA 16%; sSGA 23% both p &lt; 0.01). Specificity rates were highest for Verburg (SGA 99%; sSGA 98%) and lowest for IRIS sex-specific (SGA 94%; sSGA 92%). Results for predicting SGA with SAPO were similar for the prescriptive charts (44%), and again higher than the Verburg chart (20%). The IRIS sex-specific chart identified significantly more males as SGA and sSGA (respectively, 42%; 60%, p &lt; 0.001) than the IRIS unisex chart (respectively, 35%; 53% p &lt; 0.01). Our study demonstrates improved performance of both the IRIS sex-specific and unisex prescriptive fetal growth compared to the Verburg descriptive chart, doubling detection rates of SGA, sSGA, and SGA with SAPO. Additionally, the sex-specific chart outperformed the unisex chart in detecting SGA and sSGA. Our findings suggest the potential benefits of using prescriptive AC fetal growth charts in low-risk populations and emphasize the importance of considering customizing fetal growth charts for sex. Nevertheless, the increased sensitivity of these charts should be weighed against the decrease in specificity.

Could different cut-off values be used for 50-gram glucose tolerance test in low and high risk groups?

Objectives: There are controversies about screening strategy and cut-off levels for gestational diabetes mellitus (GDM). Here, we aimed to identify optimal cut-off values for 50-gram oral glucose tolerance testing (OGTT) in high and low risk pregnant women. Methods: A total of 500 patients who underwent two step OGTT were divided into two groups as GDM (n=31) and controls (n=469). Moreover, patients were grouped as high (n=114) and low risk (n=386) for GDM. Having≥2 risk factors such as family history of type-2 diabetes, obesity, glucosuria, previous history of GDM, macrosomia and diabetic complications were accepted as high risk. Demographic data, OGTT results, birth characteristics were recorded and compared between groups. A cut-off value for 50-gram OGTT was evaluated in low and high risk groups. Results: The 50-gram OGTT value above 140 mg/dL discriminated GDM with 100% sensitivity and 92.11% specificity in all patients (AUC=0.969, P&amp;lt;0.001). The prevalence of GDM was 19.3% in high and 2.3% in low risk group. The 50-gram OGTT value above 140 mg/dL discriminated GDM with 100% sensitivity and 94.57% specificity in high risk patients (AUC=0.992, P&amp;lt;0.001). Furthermore, 50-gram OGTT value above 149 mg/dL discriminated GDM with 100% sensitivity and 93.63% specificity in low risk patients (AUC=0.976, P&amp;lt;0.001). Conclusions: Although screening in low risk population is a debating issue worldwide, our local guidelines still recommend screening all pregnant women. We suggest that performing 100-gram OGTT only in patients who have higher values than 149 mg/dL in 50-gram OGTT can be an alternative screening strategy in low risk group.

Caesarean section rates in a tertiary teaching hospital in northern Uganda: a retrospective analysis using the robson ten group classification system

BackgroundThe Robson Ten Groups Classification System (RTGCS) is increasingly used to assess, monitor, and compare caesarean section (CS) rates within and between healthcare facilities. We evaluated the major contributing groups to the CS rate at Gulu Regional Referral Hospital (GRRH) in Northern Uganda using the RTGCS.MethodsWe conducted a retrospective analysis of all deliveries from June 2019 through July 2020 at GRRH, Gulu city, Uganda. We reviewed files of mothers and collected data on sociodemographic and obstetric variables. The outcome variables were Robson Ten Groups (1–10) based on parity, gestational age, foetal presentation, number of foetuses, the onset of labour, parity and lie, and history of CS.ResultsWe reviewed medical records of 3,183 deliveries, with a mean age of 24.6 ± 5.7 years. The overall CS rate was 13.4% (n = 427). Most participants were in RTGCS groups 3 (43.3%, n = 185) and 1 (29.2%, n = 88). The most common indication for CS was prolonged labour (41.0%, n = 175), followed by foetal distress (19.9%, n = 85) and contracted pelvis (13.6%, n = 58).ConclusionOur study showed that GRRH patients had a low-risk obstetric population dominated by mothers in groups 3 and 1, which could explain the low overall CS rate of 13.4%. However, the rates of CS among low-risk populations are alarmingly high, and this is likely to cause an increase in CS rates in the future. We recommend group-specific interventions through CS auditing to lower group-specific CS rates.

Impact of antibiotic prophylaxis on urinary tract infection recurrence in children

Introduction: Given the potential consequences associated with urinary tract infections (UTI), it has become standard practice to use continuous antibiotic prophylaxis (CAP) in children, even if controversial. We reviewed the effectiveness of CAP on recurrent UTI in a pediatric population to determine if equipoise remains and allow for a placebo control group to study the effectiveness of the vaccine MV140. Method: We completed a rapid review. We searched Medline, Embase and the Cochrane Library and data extraction was completed by a single reviewer. Our search criteria were 2005–2022, English and French language, randomized controlled trials (RCTs) and systematic reviews only. The population was 19 years and younger, including: vesicoureteral reflux (VUR), congenital anomalies of the kidneys and urinary tracts (CAKUT), and bladder and bowel dysfunction (BBD). Results: Three RCTs and three systematic reviews found a benefit for CAP, mostly for a population with VUR, and those with severe VUR have more benefit. Most studies were not able to show a difference in the rate of UTIs or new renal scars (NRS). Three RCTs found a deleterious effect with CAP. Other studies were able to prove a benefit for patients with dilatation of the urinary tract without obstruction and high-grade VUR combined with BBD. The major adverse event found was antimicrobial resistance. Conclusions: High-risk patients benefit from CAP. The potential consequences of UTIs makes it unethical to use a placebo-only control group for them; however, CAP use seems difficult to justify in a low-risk population.

Early prediction of spontaneous preterm birth before 34 gestational weeks based on a combination of inflammation-associated plasma proteins.

In order to identify and possibly offer prophylactic treatment to women at risk for preterm birth (PTB), novel prediction models for PTB are needed. Our objective was to utilize high-sensitive plasma protein profiling to investigate whether early prediction of spontaneous PTB (sPTB) before 34 gestational weeks (gw) was possible in a low-risk population. A case-control study was conducted on 46 women with sPTB before 34 gw and 46 women with normal pregnancies and term deliveries. Prospectively collected plasma sampled at gw 11 (range 7-16) and gw 25 (range 23-30) was analyzed with a high-sensitivity Proximity Extension Assay for levels of 177 inflammation-associated proteins, and statistically processed with multivariate logistic regression analysis. In the first trimester, higher levels of hepatocyte growth factor (HGF) were associated with sPTB <34 gw (OR 1.49 (1.03-2.15)). In the second trimester, higher levels of interleukin (IL)-10 (OR 2.15 (1.18-3.92)), IL-6 (OR 2.59 (1.34-4.99)), and the receptor activator of nuclear factor κB (RANK) (OR 2.18 (1.26-3.77)) were associated with sPTB <34 gw. The area under the curve for the prediction models including these proteins was 0.653 (0.534-0.759) in the first trimester and 0.854 (0.754-0.925) in the second trimester. A combination of inflammation-associated plasma proteins from the second trimester of pregnancy showed a good predictive ability regarding sPTB before 34 gw, suggesting it could be a valuable supplement for the assessment of the clinical risk of sPTB. However, although a high number (n=177) of plasma proteins were analyzed with a high-sensitivity method, the prediction of sPTB in the first trimester remains elusive.

Bioinformatics analysis of the role of lysosome-related genes in breast cancer

This study aimed to investigate the roles of lysosome-related genes in BC prognosis and immunity. Transcriptome data from TCGA and MSigDB, along with lysosome-related gene sets, underwent NMF cluster analysis, resulting in two subtypes. Using lasso regression and univariate/multivariate Cox regression analysis, an 11-gene signature was successfully identified and verified. High- and low-risk populations were dominated by HR+ sample types. There were differences in pathway enrichment, immune cell infiltration, and immune scores. Sensitive drugs targeting model genes were screened using GDSC and CCLE. This study constructed a reliable prognostic model with lysosome-related genes, providing valuable insights for BC clinical immunotherapy.

Routine transabdominal cervical length screening in mid-pregnancy for the prevention of preterm birth: Is it good enough to use as a screening test?

Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid-pregnancy may predict women at increased risk of PTB. To evaluate the utility of population-based, transabdominal cervical length (TACL) measurement screening in mid-pregnancy for PTB prediction in women. A transabdominal approach was initially performed, with a transvaginal (TVCL) approach offered when the TACL was <35 mm, could not be accurately measured, or the pregnancy had risk factors for PTB. TACL was compared to the directly related TVCL, when both were performed at the same assessment. Women with risk factors of PTB were included when they had both TACL and TVCL measurements performed at the same visit. Data were provided for 9355 singleton pregnancies from 13 participating imaging centres. A transabdominal approach was used in 9006 (96.3%), including 682 (7.3%) TVCL combined with TACL. There were 349 (3.7%) women who had TVCL only. The median TACL was longer (40 mm) than the TVCL (38 mm). In 682 paired TACL and TVCL measurements, TACL <35 mm correctly identified 96.2% of pregnancies with TVCL <25 mm, compared with 65.4% of cases when using a TACL <30 mm. A TVCL <25 mm occurred in 59 (0.6%) women. A TACL <35 mm was associated with birth <37 weeks of gestation in 12.1% of women and birth <32 weeks of gestation in 3.9%. Universal TACL is a feasible option for population screening of cervical length in a low-risk population, progressing to TVCL if the TACL is <35 mm or the cervix cannot be transabdominally accurately measured.

Neonatal Outcomes after Maternal Biomarker-Guided Preterm Birth Intervention: The AVERT PRETERM Trial.

The AVERT PRETERM trial (NCT03151330) evaluated whether screening clinically low-risk pregnancies with a validated maternal blood biomarker test for spontaneous preterm birth (sPTB) risk, followed by preventive treatments for those screening positive, would improve neonatal outcomes compared to a clinically low-risk historical population that had received the usual care. Prospective arm participants with singleton non-anomalous pregnancies and no PTB history were tested for sPTB risk at 191/7-206/7 weeks' gestation and followed up with after neonatal discharge. Screen-positive individuals (≥16% sPTB risk) were offered vaginal progesterone (200 mg) and aspirin (81 mg) daily, with twice-weekly nurse phone calls. Co-primary outcomes were neonatal morbidity and mortality, measured using a validated composite index (NMI), and neonatal hospital length of stay (NNLOS). Endpoints were assessed using survival analysis and logistic regression in a modified intent-to-treat population comprising screen-negative individuals and screen-positive individuals accepting treatment. Of 1460 eligible participants, 34.7% screened positive; of these, 56.4% accepted interventions and 43.6% declined. Compared to historical controls, prospective arm neonates comprising mothers accepting treatment had lower NMI scores (odds ratio 0.81, 95% CI, 0.67-0.98, p = 0.03) and an 18% reduction in severe morbidity. NNLOS was shorter (hazard ratio 0.73, 95% CI, 0.58-0.92, p = 0.01), with a 21% mean stay decrease among neonates having the longest stays. Sensitivity analyses in the entire intent-to-treat population supported these findings. These results suggest that biomarker sPTB risk stratification and preventive interventions can ameliorate PTB complications in singleton, often nulliparous, pregnancies historically deemed low risk.

Effect Of Transcatheter Heart Valve Size And Deployment Height On Coronary Flow Obstruction

Coronary artery disease (CAD) is commonly found in patients with aortic stenosis; therefore, its prevalence is high in patients that are candidate for transcatheter aortic valve replacement (TAVR). As the TAVR procedure is expanding into younger and lower-risk population, the importance of early CAD monitoring and detection, as well as determination of potential impact of implant design or deployment strategy on CAD progression is of great importance. In this study, we investigate the effect of transcatheter heart valve (THV) size and deployment height on coronary flow obstruction during normotensive hemodynamic flow conditions. We employ unsteady, pulsatile flow, generated by a left heart model, and utilize clinically relevant geometry, pressure, and flow waveforms. Of particular interest is to understand the interaction between THV and anatomy regarding coronary flow obstruction. For a wide range of parameters, we examine two distinct THV deployment scenarios: nominal deployment – high coronary blockage (ND-HCB), and high deployment – low coronary blockage (HD-LCB). Additionally, we investigated the impact of the locations of coronary ostia and THV commissure alignment onto the risk of coronary flow obstruction. With the aid of 2D-2C particle image velocimetry (PIV), the distinctive flow patterns within the aortic sinus space are identified from the response of the flow to the presence of THV. Comparison between two THV deployment scenarios revealed that ND-HCB configurations lead to formation of stagnant flow zones, while the HD-LCB configuration provided an adequate washout of the entire coronary sinus. The optimal washout of the aortic root sinus is achieved when the distance between native leaflets and coronary ostia is maximized. Furthermore, results showed that up to 4% improvement in the coronary flow rate can be achieved if commissure alignment procedure is performed. As the coronary artery obstruction phenomenon is additive in its nature, a pre-existing stenotic condition in association with suboptimal THV deployment may lead to increased risk of full coronary blockage and immediate need for coronary intervention. In conclusion, this study using an experimental coronary assessment tool may provide potential insights to inform pre-procedural TAVR strategies in challenging patients’ anatomies, thereby maximizing the associated benefit.