Clinical Threshold Research Articles

Development and validation of a lung cancer polygenic risk score incorporating susceptibility variants for risk factors.

Incorporating susceptibility genetic variants of risk factors has been reported to enhance the risk prediction of polygenic risk score (PRS). However, it remains unclear whether this approach is effective for lung cancer. Hence, we aimed to construct a meta polygenic risk score (metaPRS) of lung cancer and assess its prediction of lung cancer risk and implication for risk stratification. Here, a total of 2180 genetic variants were used to develop nine PRSs for lung cancer, three PRSs for different histopathologic subtypes, and 17 PRSs for lung cancer-related risk factors, respectively. These PRSs were then integrated into a metaPRS for lung cancer using the elastic-net Cox regression model in the UK Biobank (N = 442,508). Furthermore, the predictive effects of the metaPRS were assessed in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial (N = 108,665). The metaPRS was associated with lung cancer risk with a hazard ratio of 1.33 (95% confidence interval: 1.27-1.39) per standard deviation increased. The metaPRS showed the highest C-index (0.580) compared with the previous nine PRSs (C-index: 0.513-0.564) in PLCO. Besides, smokers in the intermediate risk group predicted by the clinical risk model (1.34%-1.51%) with the intermediate-high genetic risk had a 6-year average absolute lung cancer risk that exceeded the clinical risk model threshold (≥1.51%). The addition of metaPRS to the clinical risk model showed continuous net reclassification improvement (continuous NRI = 6.50%) in PLCO. These findings suggest the metaPRS can improve the predictive efficiency of lung cancer compared with the previous PRSs and refine risk stratification for lung cancer.

Cost-effectiveness intervention thresholds for romosozumab and teriparatide in the treatment of osteoporosis in the UK.

To estimate the 10-year probability of a major osteoporotic fracture (MOF) at which sequential treatment with romosozumab or teriparatide followed by alendronate, compared with alendronate alone, becomes cost-effective in a UK setting. A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), in women receiving sequential treatment with either romosozumab or teriparatide followed by alendronate, compared with alendronate alone. Patients aged 50 to 90years with a recent MOF, hip or spine fracture were followed from the start of a 5-year treatment until the age of 100years or death. The analysis had a healthcare perspective. Efficacy of romosozumab, teriparatide and alendronate was derived from phase III randomised controlled trials. Resource use and unit costs were derived from the literature. Cost-effectiveness intervention threshold (CEIT), defined as the 10-year probability of a major osteoporotic fracture at which treatment becomes cost-effective, was compared with clinically appropriate intervention thresholds for bone-forming treatment in women with very high fracture risk as recommended by the UK National Osteoporosis Guideline Group (NOGG). The base case analysis showed that sequential romosozumab-to-alendronate treatment was cost-effective from a 10-year MOF probability of 18-35% and above depending on age and site of sentinel fracture at a willingness to pay (WTP) of £30,000. For teriparatide-to-alendronate, treatment was cost-effective at a 10-year MOF probability of 27-57%. The results were sensitive to pricing of the drugs but relatively insensitive to treatment duration, romosozumab persistence assumptions, and site of sentinel fracture. The CEITs for romosozumab-to-alendronate treatment were lower than the clinical thresholds from the age of 70years meaning that treatment could be considered both cost-effective and aligned with the NOGG treatment guidelines. By contrast, for teriparatide-to-alendronate the CEITs were higher than the clinical thresholds irrespective of age. However, cost-effective scenarios were found in the presence of strong clinical risk factors in addition to a recent sentinel fracture. The results of this study indicate that sequential romosozumab-to-alendronate or teriparatide-to-alendronate treatment can be a cost-effective treatment option for postmenopausal women at very high risk of fracture.

A-321 Rethinking the Role of Race in Prenatal AFP Screening for Open Neural Tube Defects

Abstract Background The quantification of alpha-fetoprotein (AFP) in maternal serum is commonly used in prenatal screening to estimate the risk of fetal open neural tube defects (ONTDs). This involves comparing a patient’s measured AFP concentration to the median AFP for women of similar gestational age and weight, reported in AFP multiples of the median (MoM). Current guidelines recommend establishing population medians separately grouped by patients’ race, based on historical reports documenting differences in median AFP concentrations across different populations. We aimed to reevaluate this practice of race based ONTD risk stratification given the limited and questionable historical evidence as well as the small observed differences in AFP concentrations in our practice and in a recent report. Methods We collected maternal serum AFP screening data for patients between 12/30/19 and 2/9/24. Informed by the statistical methods used for clinical risk stratification, we developed two log-linear multiple variable regression models for estimating AFP: gestational age (GA), weight, and interaction terms (Model 1) and Model 1 predictors, race, and interaction terms (Model 2). AFP MoMs were calculated by dividing the measured AFP concentration by the model-estimated AFP. Results We analyzed maternal ONTD screening for 7,702 patients with singleton pregnancies. The current clinical process uses race and ethnicity as documented in the electronic health record, which was categorized as Black (N = 2,360), White (N = 3,734), Hispanic (N = 209), Asian (N = 641), and Other (N = 758). The addition of race in Model 2 included statistically significant predictors (p < 0.001) for Black (β = 0.2), Asian (β = 0.05), and Black:weight interaction (β = -5.9 x 10-4). Between Model 1 and Model 2, the mean change in AFP MoMs was -0.05, +0.03, 0.0, -0.02, and +0.01 for Black, White, Hispanic, Asian, and Other patients, respectively. 95% of Black patients had a change < 0.12 in AFP MoM and > 99% of all other patients had a change < 0.1. Using the clinical interpretative threshold, 56 (0.7%) results were considered elevated in both models, 4 (0.05%) elevated in Model 1 only (3 Black, 1 Other), and 4 (0.05%) elevated in Model 2 only (3 White, 1 Hispanic). Chart review of the 8 discordant interpretations showed small changes in MoMs (mean absolute difference = 0.09) and no cases of ONTDs. Conclusions In our health system’s population, maternal race appears to have a small statistically significant association with maternal AFP concentration, even after adjustment for weight and maternal GA. However, preliminary analyses indicate that this difference has a small impact on the clinical interpretation of these studies, with most patients classified similarly when race is not accounted for in the calculation. Further investigation is needed to clarify whether this small impact on estimation of risk warrants the continued inclusion of race in NTD screening, as well as whether other clinical, social, or community factors available for inclusion in this clinical risk stratification model would be better predictors than the poorly defined and discriminatory concept of race.

Intermanufacturer assessment of diagnostic performance of angiogenic ratio vs glycosylated fibronectin in women with suspected pre-eclampsia.

To compare the diagnostic performance of different manufacturers' immunoassays for the soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio with that of a point-of-care test for glycosylated fibronectin (GlyFn) in women with suspected pre-eclampsia (PE). This was a prospective, single-center, double-blinded, non-interventional study of East Asian women with a singleton pregnancy who presented with hypertension with or without clinical features of PE after 20 weeks' gestation between January 2020 and March 2022. Maternal serum samples were collected at the time of presentation, and subsequent management followed the departmental protocol, based on gestational age, severity of hypertension, fetal condition and presence of severe PE features. Women diagnosed with PE at presentation were excluded. PE was diagnosed according to the 2018 International Society for the Study of Hypertension in Pregnancy classification. Levels of sFlt-1 and PlGF were measured using the Cobas e411 (Roche Diagnostics), BRAHMS KRYPTOR (ThermoFisher Scientific) and iMAGIN 1800 (Ningbo-Aucheer) platforms. GlyFn levels were measured using the Lumella™ GlyFn PoC test (Diabetomics). The predictive performance of each test to rule out PE within 7 days and rule in PE within 28 days from the date of presentation was assessed. Based on the PROGNOSIS study, a sFlt-1/PlGF ratio of ≤ 38 on the Roche platform was used to predict the absence of PE within 7 days. The sFlt-1/PlGF ratio was classified as high or low using platform-specific thresholds equivalent to a Roche sFlt-1/PlGF ratio of 38, which were derived using Passing-Bablok regression. GlyFn was categorized as high or low using two reported clinical management thresholds (263 μg/mL and 510 μg/mL). Overall, 236 women with suspected PE were included, of whom 70 (29.7%) were diagnosed with PE; 36 (51.4%) and 70 (100%) developed PE within 7 days and 28 days, respectively. Eighty-eight (37.3%) women had a sFlt-1/PlGF ratio of > 38 on the Roche platform, 79 (33.5%) women had a sFlt-1/PlGF ratio of > 55 on the KRYPTOR platform and 96 (40.7%) women had a sFlt-1/PlGF ratio of > 40 on the iMAGIN 1800 platform. Furthermore, 62 (26.3%) and four (1.7%) women had a GlyFn level of > 263 μg/mL and > 510 μg/mL, respectively. The negative predictive value (NPV) of the sFlt-1/PlGF ratio measured on the Roche, KRYPTOR and iMAGIN 1800 platforms to rule out PE within 7 days after presentation was 83.3%, 82.0% and 82.9%, respectively, while that for GlyFn > 263 μg/mL and > 510 μg/mL was 82.6% and 70.4%, respectively. The corresponding positive predictive values (PPV) to rule in PE within 28 days after presentation were 50.5%, 52.3% and 46.7%, respectively, for the sFlt-1/PlGF ratio, and 35.4% and 50.0%, respectively, for GlyFn > 263 μg/mL and > 510 μg/mL. The predictive performance of different manufacturers' assays for the sFlt-1/PlGF ratio to rule in and rule out PE were similar once standardized to a common threshold. Our findings suggest that the sFlt-1/PlGF ratio and GlyFn using a cut-off of 263 μg/mL can both be utilized to rule out PE within 7 days after assessment, with a moderate NPV. The PPV for ruling in PE within 28 days remains poor. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive detection of bilirubin concentrations during the first week of life in a low-resource setting along the Thailand–Myanmar border

BackgroundNeonatal hyperbilirubinaemia (NH) is a common problem worldwide and is a cause of morbidity and mortality especially in low-resource settings.MethodsA study was carried out at Shoklo Malaria Research Unit (SMRU)...

Assessment of Racial Bias within the Risk Analysis Index of Frailty

Objective: Our objective was to assess potential racial bias within the Risk Analysis Index (RAI). Background: Patient risk measures are rarely tested for racial bias. Measures of frailty, like the RAI, need to be evaluated for poor predictive performance among Black patients. Methods: Retrospective cohort study using April 2010–March 2019 Veterans Affairs Surgical Quality Improvement Program and 2010–2019 National Surgical Quality Improvement Program data. The performance of the RAI and several potential variants were compared between Black and White cases using various metrics to predict mortality (180-day for Veterans Affairs Surgical Quality Improvement Program, 30-day for National Surgical Quality Improvement Program). Results: Using the current, clinical threshold, the RAI performed as good or better among Black cases across various performance metrics versus White. When a higher threshold was used, Black cases had higher true positive rates but lower true negative rates, yielding 2.0% higher balanced accuracy. No RAI variant noticeably eliminated bias, improved parity across both true positives and true negatives, or improved overall model performance. Conclusions: The RAI tends to predict mortality among Black patients better than it predicts mortality among White patients. As existing bias-reducing techniques were not effective, further research into bias-reducing techniques is needed, especially for clinical risk predictions. We recommend using the RAI for both statistical analysis of surgical cohorts and quality improvement programs, such as the Surgical Pause.

Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers’ sleep, oxygen saturation and heart rate on long-haul flights

BackgroundPassengers on long-haul flights frequently consume alcohol. Inflight sleep exacerbates the fall in blood oxygen saturation (SpO2) caused by the decreased oxygen partial pressure in the cabin. We investigated the...

The Utility of Magnetic Resonance Imaging-based Vertebral Bone Quality Scores as a Predictor of Cage Subsidence Following Transforaminal and Posterior Lumbar Interbody Fusion.

Retrospective study. The objectives were to determine whether vertebral bone quality (VBQ) scores are associated with interbody cage subsidence following transforaminal (TLIF) and posterior (PLIF) lumbar interbody fusions and whether there is a clinically sensitive threshold for subsidence. Interbody cage subsidence following lumbar fusion is a complication that can generate poor surgical outcomes. Prior research has correlated cage subsidence with bone mineral density. VBQ scores derived from magnetic resonance imaging (MRI) have been proposed as a tool for measuring bone mineral density, offering a potential new and convenient preoperative risk assessment tool for subsidence. The study involved patients undergoing single-level PLIF or TLIF between 2007 and 2022. Exclusions were for nondegenerative diagnoses, multilevel/revision surgeries, inadequate radiographs, missing immediate postoperative radiographs, and preoperative MRI studies older than 1 year. VBQ was calculated at L1-L4 from preoperative T1-weighted MRI images. Subsidence was assessed by changes in disc height (DH; >2mm difference) and segmental lordosis (SL; >5 degrees difference) between immediate weight-bearing postoperative and latest postoperative lateral radiographs. Statistical analysis included descriptive and inferential statistics. Subsidence was observed in 27% (SL parameter) and 47% (DH parameter) of 51 total patients. VBQ scores were significantly associated with cage subsidence based on both SL (odds ratio = 7.750, P = 0.012; correlation coefficient = 0.382, P = 0.006) and DH (odds ratio = 4.074, P = 0.026; correlation coefficient = 0.258, P = 0.057) in the combined TLIF/PLIF cohorts. In the cohort of 36 patients undergoing TLIF, a VBQ of 2.70 yielded 100.0% sensitivity and 46.2% specificity in detecting subsidence with SL measurement (area under the curve = 0.812, P < 0.001) and 86.7% sensitivity and 47.6% specificity with the DH measurement (area under the curve = 0.692, P = 0.033). We found that MRI-based VBQ scores are effective predictors of cage subsidence following TLIF surgery. A VBQ score of 2.70 demonstrated a reliable model and high sensitivity for doing so, identifying a potential clinical threshold for preoperative subsidence risk assessment. Level III.

Amaranthaceae Pollen Trends in the Air

Understanding the trends of airborne pollen allergens is of great importance given the high prevalence and socioeconomic impact of pollen-related allergic diseases globally. To study the morphological features of Amaranthaceae pollen, assess its contribution to the aerobiological situation in the city of Karakol and identify periods of increased concentration in order to improve the diagnosis and prevention of pollinosis symptoms in patients. Aerobiological sampling using a Lanzoni pollen trap was carried out from April to October over a three-year period (2015–2017) in Karakol city. Pollen identification and differential counting were performed according to current standard methodology and specially developed guides and atlases. Pollen characteristics of 4 Amaranthaceae species were visualized using scanning electron microscopy (Hitachi) to provide a detailed understanding of the surface structure and ornamentation of pollen grains. The decadal curve of Amaranthaceae pollen concentration in Karakol is unimodal, with often overlapping quantitative characteristics: 6615 (2nd decade of August 2015), 1326 (1st decade of 2016), 444 pollen grains / m3 (1st decade of 2017). At the same time, strong interannual variability of atmospheric pollen levels was observed, depending both on the pollen production of the plants themselves and on meteorological parameters, especially temperature and precipitation, changes in the traditional farming system. The response of summer-flowering Amaranthaceae weeds to climate change was demonstrated, which consists in a decrease in the annual pollen index, which corresponds to the global trend. Peak concentrations of Amaranthaceae pollen many times exceeded clinical threshold values in the air. On the surface of the Bassia scopariapollen exine, the ultrastructure study revealed the smallest (1.5-2.0 μm) granules of sporopollenin or orbicules (Ubisch bodies), which play a role in the spread of allergens. The obtained data are important in terms of increasing public awareness of the dominant pollen of the Amaranthaceae family, optimizing diagnostics, treatment and prevention of pollinosis.

Novel Biomarkers for Kidney Disease: New Frontiers in Early Diagnosis and Monitoring

Kidney diseases pose a significant threat to global public health, with early diagnosis and accurate monitoring being crucial for improving patient outcomes. However, traditional kidney disease markers such as serum creatinine and blood urea nitrogen have limitations in sensitivity and specificity. In recent years, rapid advancements in molecular biology and proteomics have led to the discovery of a series of novel biomarkers that are gradually being applied in clinical practice. This review examines novel kidney disease biomarkers, including cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). These markers not only reflect kidney injury earlier and more accurately but may also provide important bases for kidney disease classification, severity assessment, and prognosis prediction. Additionally, this paper explores the potential of multi-marker combined detection strategies in improving diagnostic accuracy. Although these novel markers show immense potential, they still face challenges such as standardization and cost-effectiveness before widespread clinical application. Future research should focus on optimizing detection methods, establishing clinical decision thresholds, and evaluating the value of these markers in personalized medicine, thereby paving new paths for precise diagnosis and treatment of kidney diseases.

Parenting stress in infancy was associated with neurodevelopment in 24-month-old children with congenital heart disease.

Having a child with congenital heart disease (CHD) is stressful for parents, but research on the impact this stress can have on child development has been lacking. We investigated the associations between parenting stress when children were infants and neurodevelopmental outcomes in toddlers with CHD. This study was carried out at the Neurocardiac Clinic at the Sainte-Justine University Hospital in Montréal, Canada. Patients born from 2012 to 2019 and followed up to 24 months of age were recruited. Parenting stress levels were measured when the child was 4-6 months and 24 months and the child's neurodevelopment was assessed at 24 months. Multiple linear regressions analyses were carried out. We studied 100 children (56% boys) with CHD. Most of the parenting stress scores were below the clinical threshold. However, they accounted for a significant part of the variance in the children's cognitive (15%-16%), receptive language (14%-15%) and gross motor outcomes (15%-18%). They had no impact on the children's expressive language or fine motor outcomes. Higher parenting stress was associated with poorer neurodevelopmental outcomes in toddlers with CHD. Early screening of parenting stress in CHD clinics is necessary to provide individualised intervention for parents and optimise neurodevelopmental outcomes in children.

Executive deficits after SARS-CoV-2 infection: A cross-sectional population study

ImportanceDespite the major implications of executive deficits in day-to-day functioning, few studies have investigated this in post-acute sequelae of SARS-CoV-2 infection using standardized measures that differentiate between aspects of executive function. ObjectiveExamine whether SARS-CoV-2 infection is associated with deficits in executive functions and if so, investigate the duration of this association. Design, Setting, and ParticipantsThe present research has a cross-sectional design and uses data from the Norwegian Covid-19 Cohort study. The current cohort (n = 8102) completed the Behavior Rating Inventory of Executive Function- Adult Version (BRIEF-A) electronically between April 2021 and September 2021. During the assessment, 4183 of the included participants had a prior positive polymerase chain reaction test (PCR) for SARS-CoV-2 and 3919 were untested or had a confirmed negative PCR test. ExposureLaboratory-confirmed SARS-CoV-2 infection. Main outcomes and measuresExecutive functions were measured using the BRIEF-A, a self-report questionnaire comprising 75 items within nine theoretically and empirically distinct clinical scales. All participants self-reported on demographical variables and comorbidity. Information on sex and age was derived from the personal identification number, and vaccination status was obtained from the Norwegian Immunization Registry (SYSVAK). ResultsParticipants with a positive SARS-CoV-2 status reported executive deficits in everyday life above the clinical threshold (T-score ≥65) more often than non-infected controls (383 vs. 225). Specifically, the SARS-CoV-2 positive status group indicated significantly more deficits related to metacognition, with the greatest difference demonstrated for working memory. This difference remained when adjusting for various demographic factors and comorbidities, with significantly greater odds of reporting above the clinical threshold following SARS-CoV-2 infection, as observed on the global executive composite score 6–12 months after infection (OR 1.97; 95% CI 1.51 to 2.55). ConclusionsOur study confirms more perceived executive deficits following SARS-CoV-2 infection compared to non-infected controls, with metacognitive aspects being the most affected. These findings shed light on the potential functional difficulties that individuals may encounter during the post-acute phase of SARS-CoV-2 infection and may guide further development of targeted interventions addressing metacognitive domains of executive functioning.

Digital speech hearing screening using a quick novel mobile hearing impairment assessment: an observational correlation study

By 2050, 1 in 4 people worldwide will be living with hearing impairment. We propose a digital Speech Hearing Screener (dSHS) using short nonsense word recognition to measure speech-hearing ability. The importance of hearing screening is increasing due to the anticipated increase in individuals with hearing impairment globally. We compare dSHS outcomes with standardized pure-tone averages (PTA) and speech-recognition thresholds (SRT). Fifty participants (aged 55 or older underwent pure-tone and speech-recognition thresholding. One-way ANOVA was used to compare differences between hearing impaired and hearing not-impaired groups, by the dSHS, with a clinical threshold of moderately impaired hearing at 35 dB and severe hearing impairment at 50 dB. dSHS results significantly correlated with PTAs/SRTs. ANOVA results revealed the dSHS was significantly different (F(1,47) = 38.1, p < 0.001) between hearing impaired and unimpaired groups. Classification analysis using a 35 dB threshold, yielded accuracy of 85.7% for PTA-based impairment and 81.6% for SRT-based impairment. At a 50 dB threshold, dSHS classification accuracy was 79.6% for PTA-based impairment (Negative Predictive Value (NPV)-93%) and 83.7% (NPV-100%) for SRT-based impairment. The dSHS successfully differentiates between hearing-impaired and unimpaired individuals in under 3 min. This hearing screener offers a time-saving, in-clinic hearing screening to streamline the triage of those with likely hearing impairment to the appropriate follow-up assessment, thereby improving the quality of services. Future work will investigate the ability of the dSHS to help rule out hearing impairment as a cause or confounder in clinical and research applications.

Do Children's Health Behaviors Buffer the Impact of Cumulative Environmental Stress on Emerging Cardiometabolic Risk?

Previous studies have found that exposure to childhood environmental stress is associated with cardiometabolic risk. However, it is not known whether individual health behaviors disrupt this relationship. This study prospectively evaluated the relationship between cumulative environmental stress in a low-income sample and cardiometabolic risk in middle childhood and examined whether child health behaviors attenuated this relationship. In a cohort of children (n=338; 57% Hispanic children; 25% Black children), environmental stressors (family and neighborhood factors representing disadvantage/deprivation) and child health behaviors (accelerometry measured physical activity; parent-reported screen time and diet recalls) were measured over 5 time points beginning when children were aged 2 to 4 years and ending when they were aged 7 to 11 years. Children's cardiometabolic risk factors (body mass index, blood pressure, triglyceride/high-density lipoprotein ratio, glucose, hemoglobin A1c, C-reactive protein) were measured at 7 to 11 years. Emerging cardiometabolic risk was defined as having ≥1 elevations that exceeded clinical thresholds. In adjusted path analyses, greater cumulative environmental stress was associated with higher likelihood of emerging cardiometabolic risk in middle childhood (P<0.001). Higher levels of moderate to vigorous physical activity and fewer sedentary minutes attenuated the positive relationship between stress and cardiometabolic risk (P<0.05). Children with >2 hours of average daily screen time had a higher likelihood of elevated cardiometabolic risk (P<0.01), but screen time did not moderate the stress-cardiometabolic risk relationship. Dietary intake was not related to cardiometabolic risk. Interventions that promote moderate to vigorous physical activity and limit sedentary behavior may have particular importance for the cardiometabolic health of children exposed to high levels of cumulative environmental stress.

Measures of Performance and Clinical Superiority Thresholds for 'Test-and-treat' Predictive Biomarkers.

Predictive biomarkers are intended to predict an individual's expected response to specific treatments. These are an important component of precision medicine. We explore measures of biomarker performance that are based on the expected probability of response to individual treatment conditional on biomarker status. We show how these measures can be used to establish thresholds at which testing strategies will be clinically superior. We used a decision model to compare expected probabilities of response of treat-all and test-and-treat strategies. Based on this, R-Shiny-based apps were developed which produce plots of the threshold positive and negative predictive values or sensitivities and specificities above which a 'test-and-treat' strategy will outperform a 'treat-all' strategy. We present a case study using data on the use of RAS status to predict response to panitumumab in metastatic colorectal cancer. Where a companion diagnostic is predictive of response to one of the treatments being compared, it is possible to estimate threshold sensitivities and specificities above which a testing strategy will outperform a treat-all strategy, based only on the odds ratio of response. Where negative and positive predictive values were used, the threshold depended on the prevalence of the biomarker-positive patients. These intuitive performance measures for predictive biomarkers, based on expected response to individual treatments, can be used to identify promising candidate companion diagnostic tests and indicate the potential magnitude of the net benefit of testing.

Quel est le seuil de détection clinique d’une inégalité de longueur des membres inférieurs ? Étude in silico de la reproductibilité et optimisation par un support gradué centimétrique

Introduction: The threshold of a Leg Length Discrepancy (LLD) by clinical examination on a sheet or centimeter paper (CP) is not known precisely whether or not it concerns limbs equipped with a hip prosthesis. We therefore conducted a prospective in silico study in order to: 1) determine the reproducibility and sensitivity of the clinical measurement of the LLD in different ideal and "degraded" clinical situations, 2) determine the threshold from which the human eye is capable of detecting a length inequality in clinic, 3) to determine whether the use of a graduated support (centimeter paper) improves the clinical measurement threshold.Hypothesis: Our hypothesis was that clinical measurement on a centimeter support would improve clinical measurement accuracy.Material and methods: This was an in silico study, the experiment was conducted on a mannequin. Different inequalities were created on a mannequin and photographed with a total of 30 inequalities from -22 to +22mm on sheet or centimeter paper (CP). This was a multicenter study, with 40 different readers. We asked the readers to make a second measurement one month later. We evaluated the inter- and intra-observer reproducibility. The error rate at the threshold of 3mm and 5mm were calculated versus the gold standard. Finally, we determined at which thresholds respectively 75% and 95% of the measurements were correct.Results: A total of 4140 measurements were performed and compared to the gold standard. With a threshold of 75% accurate measurement, the LLD detection threshold was 2.8 mm on centimeter paper and 4.5 mm on sheet. With a threshold of 95% accurate measurement, the LLD detection threshold was 3.4 mm on centimeter paper and 5.2 mm on sheet. Interobserver agreement (assessed overall on the 40 observers by Krippendorff's generalized Kappa) was 0.86 (95% confidence interval (CI95%) = 0.79 to 0.92) on CP and 0.71 (CI95% = 0.63 to 0.79) on sheet. Intra-observer agreement assessed by the intraclass correlation coefficient among observers who made 2 measurements had a median value (IQR) of 0.96 (0.94 to 0.99) on CP and 0.90 (0.83 to 0.94) on sheet.Discussion: The clinical detection threshold on sheet at the patient's bed appears close to 5mm. A more precise measurement is possible with graduated centimeter paper. A study in daily practice on patients in real situations would confirm our results.Level of evidence: III; prospective diagnostic comparative in Silico study

P012 THE EFFECT OF AGE AND LONG-TERM BLOOD PRESSURE CONTROL ON DIASTOLIC CARDIAC FUNCTION IN MASTERS ATHELETES

Background &amp; Objectives: Arterial hypertension and age underlie the risk for diastolic dysfunction and heart failure with preserved ejection fraction. Blood pressure control and physical exercise are known to ameliorate age related cardiac adaptation. Therefore, we assessed diastolic function including left atrial (LA) strains in Masters Athletes as a model for healthy ageing. Methods: At the World Masters Athletics Championships 2022 in Tampere, Finland 108 Masters Athletes partook in this field-study. Baseline data included body measures, blood pressure, age, sex and sport disciplines. Transthoracic echocardiography was performed analogous to clinical standards. Additionally, LA reservoir strain (LA-Sr) and conduit strain (LA-Scd) were assessed by speckle tracking. Results: Complete data were acquired in 108 (42, 39% female) athletes with a mean age of 62±12 (35-91) years and a body-mass-index of 23,8±2,8 kg/m2. Mean systolic blood pressure was 125±16mmHg, one third (n=36) had values ≥130mmHg. 29 performed endurance, 79 resistance disciplines. LA strain was not influenced by sport discipline nor blood pressure, neither in dichotomization for clinical thresholds nor in linear correlation. Female athletes showed higher LA reservoir and conduit strain (LA-Sr: 29.1±5.3% versus 27±5.5%, p=0.046; LA-Scd: 16.6±6% versus 13.9±5.4%, p=0,018). With increasing age, body-mass-index and left-ventricular-mass-index, LA reservoir and conduit strains declined significantly, independent of blood pressure. In Masters Athletes that did not meet echocardiographic criteria of diastolic dysfunction we found significantly higher LA reservoir and conduit strains than in those with 2 criteria met (LA-Sr 29.8±5.2% versus 25.4±6.6%, p=0.007; LA-Scd -17.3±6% versus -13.4±6.5%, p=0.030). Conclusion: In the specialized cohort of Masters Athletes LA reservoir and conduit strain showed the same dependency from age, body-mass-index and left-ventricular-mass-index as other parameters of diastolic function with higher values in females. Furthermore, impaired diastolic function was associated with decreased LA strain. Therefore, assessment of LA strain seems beneficial beyond classical echocardiographic measurements in determining diastolic function in the elderly. Surprisingly, long-term blood pressure control by physical exercise had no effect on LA strains.

Ten-Year Outcomes in Patients Aged 40 Years and Older After Primary Arthroscopic Treatment of Femoroacetabular Impingement With Labral Repair

Background: Arthroscopic labral repair has been shown to result in favorable short- and midterm outcomes; however, the durability of outcomes specifically in older patients remains underreported. Purpose: To (1) report prospectively collected hip preservation rates and patient-reported outcome measures (PROMs) at a minimum 10-year follow-up in patients aged ≥40 years after primary hip arthroscopy with labral repair and (2) perform a matched analysis comparing patients aged ≥40 years with patients aged <40 years. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed on all patients who underwent primary hip arthroscopy between February 2008 and December 2011. Patients aged ≥40 years who underwent labral repair were included. Preoperative and minimum 10-year follow-up scores were collected for multiple PROMs. Propensity score matching was utilized to compare these patients with a cohort of patients <40 years. Results: Of the 113 hips eligible, 91 hips (80.5%) on 85 patients (6 bilateral) had a minimum 10-year follow-up. There were 58 women (68%) and 27 men (32%) with a mean age and body mass index of 47.8 years and 25.8, respectively. The hip preservation rate for patients aged ≥40 years was 78%, with 20 patients requiring arthroplasty during the study period. There was significant improvement in all PROMs from baseline to minimum 10-year follow-up with high rates of achieving the minimal clinically important difference and Patient Acceptable Symptom State clinical outcome thresholds. In total, 69 patients aged ≥40 years were propensity matched to 107 patients <40 years. Patients ≥40 tended to have a lower hip preservation rate (81.2% vs 91.6%; P = .06), while patients in the younger cohort had significantly higher rates of secondary hip arthroscopy (14% vs 3%; P = .02). Improvement in PROMs was comparable between the groups. Conclusion: Patients ≥40 years who underwent primary hip arthroscopy with labral repair demonstrated a hip preservation rate of 78%, significant and durable improvement in PROMs, and high rates of satisfaction at a minimum 10-year follow-up. Matched analysis with patients <40 years revealed comparable improvement in patient-reported outcomes between the 2 groups, with a tendency to a higher level of arthroplasty in patients ≥40 years.

Pathways between grief, depression, hopelessness, reasons for living, and suicidal ideation in bereaved individuals

BackgroundAssociations between comorbid depression and grief with suicidal ideation (SI) have been inconsistent. To identify at-risk individuals, it is important to determine the role of symptom severity by examining both continuous and clinical-threshold grief and depression, in addition to other factors (i.e., hopelessness, reasons for living—RFL) associated with SI. MethodsParticipants (n = 216) bereaved by combat, accident, or suicide completed an online survey. Associations between depression, grief, SI, RFL, and hopelessness were examined by multivariable logistic regressions and structural equation modeling (SEM). ResultsAcross the sample, hopelessness and RFL were associated with SI while continuous measures of grief and depression were not. In contrast, clinical-threshold grief, clinical-threshold depression, hopelessness, and RFL each were associated with SI. In addition, of the grief characteristics, yearning was the most robust correlate of SI, and Survival/Coping Beliefs (SCB) was the RFL most associated with SI. SEM indicated that direct paths between grief and SI, hopelessness and SI, and RFL and SI were significant, but not between depression and SI. Instead, depression had a strong direct effect on hopelessness, and hopelessness had a direct effect on SI. DiscussionResults are consistent with previously-identified associations between SI and clinical levels of depression and grief. More nuanced findings suggest hopelessness, yearning, and SCB as additional targets for reducing risk for SI in bereaved individuals regardless of whether they meet clinical thresholds for grief or depression.

Investigating the utility of the AQ-10 in children and adolescents assessed in an outpatient ARFID clinic.

The high co-occurrence of autism and eating disorders is well established, including for those with Avoidant Restrictive Food Intake Disorder (ARFID). It is therefore important to consider autism and identify possible autism when people present to eating disorder services to ascertain whether further assessment is indicated, to support clinical formulation and to make appropriate adaptations during interventions. This paper explores the utility of a validated autism screening measure, the AQ-10, in a population of children and adolescents who presented to an outpatient eating disorders clinic for an assessment of possible ARFID. Over 19 months, 335 young people were assessed and 246 families with children aged between 4 and 17 years completed one of three versions of the AQ-10 (Child, Adolescent, and Adult), as part of a battery of routinely administered pre-assessment questionnaires. Results indicated that 80.2% (n = 69) of those with an existing autism diagnosis scored above clinical threshold of ≥6 (M = 7.2, SD = 1.9), 43.9% (n = 43) of those queried to be autistic scored above clinical threshold (M = 5.2, SD = 2.5), and 6.5% (n = 4) of non-autistic individuals scored above clinical threshold (M = 2.8, SD = 1.8). Additionally, the AQ-10 satisfactorily discriminated between those with a known autism diagnosis and those who are not autistic across all age groups and sex. We conclude that the AQ-10, alongside a comprehensive clinical assessment and clinical judgment, is a useful screening tool that can support clinicians to identify appropriate onward referrals for autism assessments, aid clinical formulation, and consider appropriate adaptations and reasonable adjustments during ARFID interventions.