Treatment Thresholds Research Articles

Management of bone health in idiopathic inflammatory myopathies: A two-center audit in the United Kingdom and Hong Kong.

Patients with inflammatory idiopathic myopathies (IIM) face elevated risks of osteoporosis and fragility fracture. To evaluate current practice relating to bone health in adult patients with IIM in the United Kingdom and Hong Kong (HK). Patients were identified from IIM patient lists. Demographics, osteoporosis risk factors, DXA scans, and bone protection treatment were recorded. Adherence to regional standards was evaluated for each center. Following this, in the United Kingdom, up-to-date DXA scans were performed. Of 136 patients identified, 51 met selection criteria (UK, n = 20, HK, n = 31). Mean age in the United Kingdom was 59 (IQR 54-66); in Hong Kong, 65 (IQR 52.5-70). Most were female (UK 70%; HK 77%), current or previous steroid treatment was common (UK 90%; HK 100%) and some had experienced fragility fracture (UK 15%; HK 9%). The mean daily dose of prednisolone that patients were prescribed during the study was 12.5 mg (UK) and 14.3 mg (HK). Some patients had had a DXA scan (UK 50%; HK 35%) though several were outdated. Among those with BMD measured (UK, n = 20; HK, n = 11), osteopenia prevalence was 35% (UK) and 36% (HK) while osteoporosis was 5% (UK) and 36% (HK). Notably, 25% (UK) and 64% (HK) exceeded treatment thresholds. Treatments included anti-osteoporotic agents (UK 55%; HK 15%), Vitamin D/calcium supplements (UK 95%; HK 52%), or no treatment (UK 5%, HK 15%). Poor compliance with guidelines exists in both centers, particularly around investigation and monitoring of bone health for IIM patients. Integrated care models and increased resource allocation to bone health are imperative to improve management of this aspect of IIM.

Revisiting secondary mitral regurgitation threshold severity: insights and lessons from the RESHAPE-HF2 trial.

This article revisits the severity threshold for secondary mitral regurgitation (MR), focusing on insights and lessons from the RESHAPE-HF2 trial. It aims to challenge the traditional effective regurgitant orifice area (EROA) threshold of ≥0.40 cm2 used for intervention, suggesting that earlier intervention may benefit patients with lower EROA. It also explores how transcatheter edge-to-edge repair (TEER) improves outcomes in patients with secondary MR and assesses the impact of left ventricular (LV) remodeling on treatment success. The RESHAPE-HF2 trial evaluated the use of TEER in patients with moderate-to-severe secondary MR, comparing outcomes in those with an EROA ≥0.2 cm2 and no extensive LV remodeling. TEER significantly reduced heart failure hospitalizations and improved quality of life in these patients. This supports the notion that patients with less severe MR, who still show symptoms despite optimal medical therapy, may benefit from earlier intervention. Comparisons with COAPT and MITRA-FR trials underscored the importance of selecting patients based on MR severity relative to LV dilatation. The RESHAPE-HF2 trial highlights the need to reconsider the current EROA threshold for secondary MR intervention. TEER has shown to be beneficial even in patients with lower MR severity, suggesting that earlier intervention could improve outcomes. A more dynamic and integrated approach, considering both MR severity and LV remodeling, is essential for optimizing patient selection and treatment success.

Stakeholder-informed positivity thresholds for disease markers and risk scores: a methodological framework and an application in obstructive lung disease

ObjectivesA positivity threshold is often applied to markers or predicted risks to guide disease management. These thresholds are often decided exclusively by clinical experts despite being sensitive to the preferences of patients and general public as ultimate stakeholders. Study Design and SettingWe propose an analytical framework for quantifying the net benefit (NB) of an evidence-based positivity threshold based on combining preference-sensitive (eg, how individuals weight benefits and harms of treatment) and preference-agnostic (eg, the magnitude of benefit and the risk of harm) parameters. We propose parsimonious choice experiments to elicit preference-sensitive parameters from stakeholders, and targeted evidence synthesis to quantify the value of preference-agnostic parameters. We apply this framework to maintenance of azithromycin therapy for chronic obstructive pulmonary disease using a discrete choice experiment to estimate preference weights for attribute level associated with treatment. We identify the positivity threshold on 12-month moderate or severe exacerbation risk that would maximize the NB of treatment in terms of severe exacerbations avoided. ResultsIn the case study, the prevention of moderate and severe exacerbations (benefits) and the risk of hearing loss and gastrointestinal symptoms (harms) emerged as important attributes. Four hundred seventy seven respondents completed the discrete choice experiment survey. Relative to each percent risk of severe exacerbation, preference weights for each percent risk of moderate exacerbation, hearing loss, and gastrointestinal symptoms were 0.395 (95% confidence interval [CI] 0.338–0.456), 1.180 (95% CI 1.071–1.201), and 0.253 (95% CI 0.207–0.299), respectively. The optimal threshold that maximized NB was to treat patients with a 12-month risk of moderate or severe exacerbations ≥12%. ConclusionThe proposed methodology can be applied to many contexts where the objective is to devise positivity thresholds that need to incorporate stakeholder preferences. Applying this framework to chronic obstructive pulmonary disease pharmacotherapy resulted in a stakeholder-informed treatment threshold that was substantially lower than the implicit thresholds in contemporary guidelines. Plain Language SummaryDoctors often compare disease markers (such as laboratory results) or risk scores for a patient with cut-off values from guidelines to decide which patients need to be treated. For example, guidelines recommend that patients whose 10-year risk of heart attack is more than 10% be given statin pills. However, guidelines that recommend such treatment rules might not consider what matters most to patients (like how much they do not like side effects of the drugs). In this study, we propose a mathematical method where preferences of individuals on the trade-off between treatment benefits and harms can be used to determine the best treatment rule. We apply this method to the choice of antibiotic therapy for patients with lung airway diseases. We find that, given patient and public preferences on treatment benefit and risks, those with a 12% or more risk of experiencing a lung attack should receive antibiotic therapy. This patient-oriented cut-off is significantly lower than the cut-off values currently used by guidelines, which are in the 60%–70% range. We recommend applying this method whenever scientists must make recommendations on treatment rules where patient or public preferences might influence those rules.

Risk of Cardiovascular Events in Adults Aged 40 to 79 Years with Diagnosed Hypertension, High Cholesterol, and/or Diabetes but Not on Medications: Findings from Nationwide Cross-Sectional Studies.

Many people with diagnosed hypertension, high cholesterol, and/or diabetes are not receiving drug treatment, partly because they perceive their cardiovascular disease (CVD) risk as low. This study aimed to quantify the risk for future CVD events, either first or recurrent, in people with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications for any of these conditions. Participants aged 40-79 years who had been diagnosed with hypertension, high cholesterol, and/or diabetes but were not on medications were identified from National Health and Nutrition Examination Surveys cycles 1999 to 2018. Among them, those with known CVD and those without known CVD but with complete data for estimating their 10-year CVD risk were included in this study. The participants were classified as (1) "high-risk" if they had known CVD or a 10-year predicted CVD risk ≥ 7.5% or (2) "low-risk" if they had a 10-year predicted CVD risk < 7.5%. Of the 5187 participants included, 2201 had known major CVD (n = 490, 9.45%) or a 10-year predicted CVD risk ≥ 7.5% (n = 1711, 32.99%), corresponding to a weighted proportion of 34.83% (95% CI: 33.15 to 36.51%) in the US general population. The proportions of high-risk participants were much higher in the elderly (65.50% for 60-69 years and 97.86% for 70-79 years), males (45.13%), and non-Hispanic Blacks (42.15%) than in others (all p < 0.001). These patterns were consistent across survey cycles during 1999-2018. Additional analyses that classified the participants into groups above or below the treatment threshold (rather than high- or low-risk groups) according to current guidelines yielded similar results. A comparison of the 2201 untreated high-risk participants with other participants who had been diagnosed with hypertension, high cholesterol, and/or diabetes and were on medications for these conditions showed that "lower BMI", "smaller waist circumference", and a "non-diabetic" status, among others, were associated with a higher likelihood of "not taking medications". In conclusion, approximately one-third of the US adults aged 40 to 79 years with diagnosed hypertension, high cholesterol, and/or diabetes but not on medications had known CVD or a 10-year predicted CVD risk ≥ 7.5%, and this proportion was little changed over the past two decades. Interventions targeted at the subgroups with particular characteristics identified in this study may help improve the management of CVD and its risk factors.

Digitalising Clinical Guidelines: The Challenge of Patient's Preferences.

Will digitalised clinical guidelines be compatible with individualised and personalised patient care if the disease definitions and classifications used within them contain embedded preferences? Taking bone health as a case study, we found the dominant definition of osteoporosis installs the consensus preference judgement of a 1992 International Expert Committee in the form of a threshold cut-off on the bone mineral density continuum. We found that subsequent UK clinical guidelines follow suit on this diagnostic threshold, but also endorse preference-sensitive thresholds for interventions to prevent fractures, including ones underpinned by cost-effectiveness analysis. The resulting pre-emption of patient's preferences needs to be removed if 'computable' guidelines are to be reconcilable with personalised care. The challenges to be met in digitalisation therefore include major conceptual ones as well as the technical ones that are currently the almost exclusive focus.

Ruptured AAA: bridging the gap between international guidelines and local clinical realities

BackgroundTreatment of asymptomatic Abdominal Aortic Aneurysms (AAA) presents a clinical challenge, requiring a delicate balance between rupture risk, patient comorbidities, and intervention-related complications. International guidelines recommend intervention for specific AAA size thresholds, but these are based on historical trials with limited female representation. We aimed to analyse disease characteristics, AAA size at rupture, and intervention outcomes in patients with ruptured AAA from 2009 to 2023 to investigate the gap between guidelines and local realities.MethodsThis single-centre retrospective cohort study analysed electronic health records of patients treated for a ruptured AAA, excluding those who were managed palliatively. The study assessed patients’ demographics, risk factors, comorbidities, clinical presentation, radiological characteristics, and outcomes.ResultsOf 164 patients (41 females, 123 males, median age 73.5), 93.3% presented with abdominal or back pain. The median AAA size at rupture was 8.0 cm in males and 7.6 cm in females. No significant correlations were found between demographic characteristics, risk factors, AAA size, repair modality, and outcomes. Trends show a decline in AAA prevalence and rupture rates, aligning with global health initiatives. Post-intervention survival rates at 30 days were 70.7% (67.5% in males and 80.0% in females), and at 2 years were 65.85% (61.7% in males and 70.0% in females).ConclusionEvolving AAA trends and improved post-intervention survival rates warrant a critical reassessment of existing intervention recommendations. Adjusting intervention thresholds to larger sizes may be justified to optimise the risk-benefit ratio.

Combining proximal and remote sensing to assess 'Calatina' olive water status.

Developing an efficient and sustainable precision irrigation strategy is crucial in contemporary agriculture. This study aimed to combine proximal and remote sensing techniques to show the benefits of using both monitoring methods, simultaneously assessing the water status and response of 'Calatina' olive under two distinct irrigation levels: full irrigation (FI), and drought stress (DS, -3 to -4 MPa). Stem water potential (Ψstem) and stomatal conductance (gs) were monitored weekly as reference indicators of plant water status. Crop water stress index (CWSI) and stomatal conductance index (Ig) were calculated through ground-based infrared thermography. Fruit gauges were used to monitor continuously fruit growth and data were converted in fruit daily weight fluctuations (ΔW) and relative growth rate (RGR). Normalized difference vegetation index (NDVI), normalized difference RedEdge index (NDRE), green normalized difference vegetation index (GNDVI), chlorophyll vegetation index (CVI), modified soil-adjusted vegetation index (MSAVI), water index (WI), normalized difference greenness index (NDGI) and green index (GI) were calculated from data collected by UAV-mounted multispectral camera. Data obtained from proximal sensing were correlated with both Ψstem and gs, while remote sensing data were correlated only with Ψstem. Regression analysis showed that both CWSI and Ig proved to be reliable indicators of Ψstem and gs. Of the two fruit growth parameters, ΔW exhibited a stronger relationship, primarily with Ψstem. Finally, NDVI, GNDVI, WI and NDRE emerged as the vegetation indices that correlated most strongly with Ψstem, achieving high R2 values. Combining proximal and remote sensing indices suggested two valid approaches: a more simplified one involving the use of CWSI and either NDVI or WI, and a more comprehensive one involving CWSI and ΔW as proximal indices, along with WI as a multispectral index. Further studies on combining proximal and remote sensing data will be necessary in order to find strategic combinations of sensors and establish intervention thresholds.

Population structure, spatial aggregation, and sampling plan for the Texas citrus mite, Eutetranychus banksi (Acari: Tetranychidae) on citrus.

Eutetranychus banksi (McGregor) (Acari: Tetranychidae) is an invasive spider mite native to the Americas. In 2013 it invaded the main citrus-growing area in Spain producing significant damage and requiring chemical treatments. This work examines its population structure, spatial distribution and presents a sampling plan, which will assist in developing an integrated pest management (IPM) strategy. There were differences in the population structure on fruits and leaves, as well as between leaves from different flushes with fluctuations over time correlated with variations in sex ratio. No differences in aggregation at the different plant strata were found; however, immature stages showed a higher aggregation than adults, with females being the sex with the lowest aggregation. There was a high correlation between E. banksi motile forms and adult females with the total population, thus both were used as reference stages to develop sampling plans. We recommend binomial sampling of 100 leaves for female monitoring, sampling two leaves per tree on 25 trees per transect regularly spaced along two diagonal transects, the first oriented northeast to southwest and the second northwest to southeast. To be more accurate, it is possible to survey the presence/absence of motile forms. In this case, four leaves per tree in 50 trees per transect should be monitored. This study has resulted in the first sampling plan for E. banksi, one of the most damaging citrus mite species described so far. The binomial sampling plan involves monitoring reference developmental stages, as well as a reasonable sample size that makes it applicable in field sampling for decisions making based on a future intervention threshold. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Umbilical Cord pH Levels and Neonatal Morbidity and Mortality

Umbilical cord pH (UC-pH) level is an important objective indicator of intrapartum fetal hypoxia and is used to predict neonatal morbidity and mortality. A UC-pH value of less than 7.00 is often defined as a threshold for severe acidosis, but existing evidence is divergent and largely based on UC-pH measurements from selected populations; consequently, the results are challenging to interpret. To investigate the association between UC-pH levels and the risk of adverse neonatal outcomes in a national setting with universal UC-pH measurement. This national, population-based cohort study included all liveborn, singleton, full-term infants without malformations born in Denmark from January 1, 2012, to December 31, 2018. Data were analyzed from January 1, 2023, to March 1, 2024. Umbilical cord pH level categorized as less than 7.00, 7.00 to 7.09, 7.10 to 7.19 and 7.20 to 7.50 (reference group). The primary outcome was a composite of severe adverse neonatal outcomes: neonatal death, therapeutic hypothermia, mechanical ventilation, treatment with inhaled nitric oxide, or seizures. Secondary outcomes were individual components of the primary outcome, Apgar score, respiratory outcomes, and hypoglycemia. Data are presented as adjusted risk ratios (ARRs) with 95% CIs. Among the 340 431 infants included, mean (SD) gestational age was 39.9 (1.6) weeks; mean (SD) birth weight was 3561 (480) g; and 51.3% were male. Umbilical cord pH of less than 7.20 was observed more often among infants with a gestational age of 40 or 41 weeks (31.6%-33.6% compared with 18.2%-20.2% at a gestational age of 39 weeks) and among male infants (53.9%-55.4% vs 44.6%-46.1% among female infants). Compared with the pH reference group (576 of 253 540 [0.2%]), the risk for the primary outcome was increased for the groups with UC-pH levels of less than 7.00 (171 of 1743 [9.8%]), 7.00 to 7.09 (101 of 11 904 [0.8%]), and 7.10 to 7.19 (259 of 73 244 [0.4%]). Comparable patterns were observed for the individual outcomes, except for neonatal death, which was only increased in the group with UC-pH levels of less than 7.10. The risk of treatment with continuous positive airway pressure was increased when UC-pH levels were less than 7.20, and the risk of hypoglycemia was 21.5% if UC-pH levels were less than 7.10. In this cohort study of 340 431 newborn infants, results support and extend previous studies indicating a higher risk of adverse outcomes even at UC-pH levels above 7.00. The threshold for more intensive observation and treatment may be reconsidered.

Discordant Treatment Goals for PatientsWith Atrial Fibrillation and Clinical Trials Metrics.

Most clinical trials define successful atrial fibrillation (AF) treatment as no AF episodes longer than 30 seconds. Yet, there has been minimal study of how patients define successful treatment and whether their perspectives align with trial outcomes. Survey patients with AF to identify: 1) what aspect of AF is most important to address (frequency, duration, or severity of AF episodes); 2) what AF burden would be considered acceptable to consider treatment successful; and 3) to establish patient preferences for successful treatment thresholds for a validated patient-reported outcome (PRO) score. We surveyed patients receiving active care for AF at a single tertiary care center modeled after the Toronto AF Severity Scale (AFSS). The survey consisted of current and "successful treatment" AF frequency, burden, and symptom domains; and baseline socioeconomic information. Of 7,000 invitations, 852 individuals completed the survey (12% response) with a mean age of 65 ± 13 years, 36.5% were female, and they had a mean CHA2DS2-VAsc score of 2.9 ± 1.9. Overall, 114 (13%) selected a decrease in AF episode duration as their top treatment priority, 505 (59%) episode frequency, and 230 (27%) episode severity. Overall, 207 (24%) patients would only consider a treatment successful if they never had AF again, whereas 645 (76%) patients considered success to be fewer AF episodes. A total of 341 (40%) patients would only consider a treatment successful if AF episodes lasted less than a few minutes, whereas 509 (60%) patients would accept AF episodes lasting >30minutes. An AFSS symptom score≤5 was considered a good outcome by 80% of respondents. Patients prioritize decreased AF frequency over improvements in severity or duration, and an AFSS≤5 would be a reasonable outcome of AF treatment. Most patients would consider treatment successful if they had more than 1 AF episode lasting longer than 30 seconds. Future clinical trial design should consider patients' perspectives when designing outcomes.

Early Experience With the Iliac Branch Endoprosthesis (IBE) in Managing Iliac Aneurysms.

Aim The objective of this study is to evaluate the feasibility of using iliac branch endoprosthesis (IBE) devices and to examine their short-term outcomes. Materials and methods This was a descriptive, retrospective observational study involving 15 patients diagnosed with either aortoiliac or isolated iliac artery aneurysms and treated with an IBE device. Data were collected for patients who received IBE devices at Glan Clwyd Hospital in Rhyl, United Kingdom, from February 2020 to May 2023. Results Most patients presented with asymptomatic aneurysms; 86.7% (n = 13) had bilateral common iliac artery (CIA) aneurysms. The mean diameter of the CIA was 38.7 ± 8.8 mm, and the mean diameter of the abdominal aortic aneurysm (AAA) was 39.8 ± 23 mm. For the indications of IBE use, 60% (n = 9) of the patients had iliac aneurysms reaching the intervention threshold, 20% (n = 3) had AAA reaching the threshold, and 20% (n = 3) had aortoiliac aneurysms reaching the threshold. The majority of patients underwent bilateral femoral access (86.7%; n = 13), while 13.3% (n = 2) required both femoral and brachial access. Technical success was achieved in all cases. Aside from 20% (n = 3) of cases where the sac size remained static, the majority of patients (80%; n = 12) experienced sac regression. All patients were free from buttock claudication. A type II endoleak was observed in 33.3% (n = 5) of patients. No reinterventions were reported. The mean primary patency was 30.9 ± 0.7 months, and the follow-up period ranged from 12 to 36 months. Conclusions IBEs are an effective medical device, demonstrating a high rate of technical success, minimal need for additional procedures, and a low incidence of complications while maintaining a satisfactory rate of primary patency.

Projected Changes in Statin and Antihypertensive Therapy Eligibility With the AHA PREVENT Cardiovascular Risk Equations

Since 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) have recommended the pooled cohort equations (PCEs) for estimating the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). An AHA scientific advisory group recently developed the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations, which incorporated kidney measures, removed race as an input, and improved calibration in contemporary populations. PREVENT is known to produce ASCVD risk predictions that are lower than those produced by the PCEs, but the potential clinical implications have not been quantified. To estimate the number of US adults who would experience changes in risk categorization, treatment eligibility, or clinical outcomes when applying PREVENT equations to existing ACC and AHA guidelines. Nationally representative cross-sectional sample of 7765 US adults aged 30 to 79 years who participated in the National Health and Nutrition Examination Surveys of 2011 to March 2020, which had response rates ranging from 47% to 70%. Differences in predicted 10-year ASCVD risk, ACC and AHA risk categorization, eligibility for statin or antihypertensive therapy, and projected occurrences of myocardial infarction or stroke. In a nationally representative sample of 7765 US adults aged 30 to 79 years (median age, 53 years; 51.3% women), it was estimated that using PREVENT equations would reclassify approximately half of US adults to lower ACC and AHA risk categories (53.0% [95% CI, 51.2%-54.8%]) and very few US adults to higher risk categories (0.41% [95% CI, 0.25%-0.62%]). The number of US adults receiving or recommended for preventive treatment would decrease by an estimated 14.3 million (95% CI, 12.6 million-15.9 million) for statin therapy and 2.62 million (95% CI, 2.02 million-3.21 million) for antihypertensive therapy. The study estimated that, over 10 years, these decreases in treatment eligibility could result in 107 000 additional occurrences of myocardial infarction or stroke. Eligibility changes would affect twice as many men as women and a greater proportion of Black adults than White adults. By assigning lower ASCVD risk predictions, application of the PREVENT equations to existing treatment thresholds could reduce eligibility for statin and antihypertensive therapy among 15.8 million US adults.

Effects of minimum dissolved oxygen setpoints for aeration in semi-intensive pond production of Pacific white shrimp (Litopenaeus vannamei)

Aeration is considered one of the most critical factors in shrimp farming as it affects the metabolism of shrimp and other living organisms within a pond. Maintenance of proper dissolved oxygen (DO) concentrations is critical, as low DO can cause stress, lower resistance to disease, and inhibit growth. Although the effects of single, short-term hypoxia events have been widely studied, little to no research has examined effects of repeated exposure to hypoxia during multiple diurnal cycles that shrimp may experience in aquaculture ponds. Even though the concept is simple, proper DO management is not simple. It is dependent on numerous factors and often based on anecdotal recommendations. The present trial was conducted to help elucidate the effects of DO management strategies on shrimp performance. The trial examined the effects of three different DO set points for automatic aeration on shrimp production and water quality parameters in earthen ponds. In sixteen earthen ponds (0.1 ha), juvenile Pacific white shrimp (⁓0.030 g) were stocked at a density of 25ind/m2. Minimal DO setpoints that activated automatic aeration in each of the treatments were 2.5, 3.5, and 4.5 mg O2/L, respectively. Shrimp were fed using the AQ1 passive acoustic monitoring system that was set to not feed while DO was below the threshold of a given treatment. Each of the treatments was applied to 5 ponds, except for treatment 1 (2.5 mg/L) which was applied 6 ponds as it was considered of higher risk. Shrimp growth performance and water quality indicators were monitored weekly. At the end of the 79–81-day trial, results showed that different aeration control treatments had no significant effect in terms of growth performance, feed inputs or productivity parameters. The final weight of the shrimp ranged between 33.3 and 33.6 g, with average final yields of 7500–8500 kg per ha. Nonetheless, mean electrical costs differed significantly between treatments, with higher DO setpoints treatments exhibiting a higher aeration cost with no discernible benefit. Water quality parameters showed no significant difference, except for morning and afternoon DO concentrations.

Re-evaluating treatment thresholds in patient blood management: Female patients experience more perioperative anaemia and higher transfusion rates in major elective surgery.

By optimizing erythropoiesis, patient blood management (PBM) programmes can reduce transfusions, lower mortality and provide cost-effective care. While definitions of anaemia have historically varied by sex, for the purposes of PBM, anaemia is defined as a haemoglobin <130 g/L. Our objective was to describe whether perioperative anaemia and transfusion rates in the PBM setting vary by sex. We conducted a retrospective study of the Ontario Nurse Transfusion Coordinators Program (ONTraC) database from 2018 to 2022. ONTraC collects data from 25 Ontario hospitals which together account for >70% of Ontario's provincial blood use (~400,000 units per year). We collected data on patients undergoing elective isolated coronary artery bypass graft surgery (CABG), open heart valve replacement, CABG plus valve replacement, single-knee arthroplasty and single-hip arthroplasty. From 2018 to 2022, 17,700 patients were included in the ONTraC program; 47% were females (N = 8376). Across almost all years and procedures, females were found to have a significantly lower pre-operative, nadir and discharge haemoglobin as compared with males, irrespective of PBM interventions. Transfusion rates were significantly higher for females; this was most pronounced in cardiac surgery. Females experienced more perioperative anaemia and higher transfusion rates. Historic sex-specific definitions of anaemia may contribute to a greater tolerance of anaemia in females. Prioritizing females for multimodal PBM and consistently achieving a pre-operative haemoglobin >130 g/L may reduce the amount of red blood cell (RBC) transfusions that female patients receive.

Intervention at an early threshold for post-hemorrhagic ventricular dilatation in preterm infants: a systematic review and meta-analysis.

Very few adequately powered studies exploring early thresholds for intervention in the management of post-hemorrhagic ventricular dilatation (PHVD) in preterm infants have identified consistent neurodevelopmental advantages at 12-30months. We aimed to conduct a meta-analysis on the efficacy and safety of early versus conservative thresholds for intervention, primarily aimed at normalizing cerebrospinal fluid (CSF) pressure, in the management of PHVD in preterm infants. Multiple databases were searched for eligible papers, and prospective randomized trials involving preterm infants were selected. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). The main outcome was survival without moderate-to-severe neurodevelopmental impairment at 12-30months. Ten articles representing seven randomized trials comparing early versus conservative thresholds for interventions were included. Five trials (n = 545 infants) reported no difference in the main outcome between early and conservative groups [RR 0.99 (0.71, 1.37)]. Sensitivity analysis excluding data from a medication trial did not alter the main outcome [RR 1.15 (0.95, 1.39)]. Infants in the early threshold group received significantly more interventions [RR 1.48 (1.05, 2.09)]. Deaths before discharge/during the initial study period [RR 1.04 (0.70, 1.54)] or a composite of death or shunt insertion [RR 1.04 (0.86, 1.27)] were comparable between the two groups. Early intervention for PHVD, before a clinical or ultrasound threshold is met, leads to additional clinical procedures but does not improve survival without moderate-severe neurodevelopmental impairment at 12-30months. Caution should be exercised in interpreting these results due to significant variation between the studies. Supplementary file 3 (MP4 131172kb).

A modified handling stability control strategy for steer-by-wire vehicles based on variable steering ratio and active front steering control

Steer-by-wire (SBW) systems with steering actuator motors rotating the front wheels allow more flexibility for handling stability control; however, determining the desired steering angle and accurately tracking the desired steering angle are still key challenges. Therefore, a modified handling stability control strategy for handling stability is proposed in this paper. Firstly, based on the normal function, a unified variable steering ratio (UniVSR) model that varies with vehicle speed and steering wheel angle is developed. Then, the UniVSR model parameters are optimized by particle swarm optimization (PSO) algorithm in speed segments to improve the steering sensitivity at low speeds and the stability at medium and high speeds. Next, the active front steering (AFS) controller that considers the intervention timing and intervention threshold is proposed to improve the stability of the SBW vehicle under the driving conditions of low-adhesion road, split-μ road, and lateral wind interference. Lastly, the linear active disturbance rejection control (LADRC) based angle tracking control algorithm is presented to guarantee the desired angle tracking accuracy of the steering actuator motor under both internal parameter and external torque perturbations. The simulations validate the effectiveness of the proposed UniVSR model and AFS controller in improving handling stability.

Endovascular Treatment for Basilar Artery Occlusion.

Basilar artery occlusion (BAO) is a neurological emergency associated with a high risk for adverse outcomes. This review provides evidence on the therapeutic efficacy of intravenous thrombolysis (IVT) and endovascular therapy (EVT) in the treatment of BAO. Historically considered the primary intervention for acute ischemic stroke, IVT has been progressively combined with EVT, which has emerged from recent studies demonstrating clinical benefits, notably in patients presenting with severe stroke. Several randomised controlled trials have shown that EVT improves patient outcomes in select clinical contexts. Future research directions could address therapeutic treatment thresholds, combination strategies, and long-term outcomes.

Estimating uncertainty when providing individual cardiovascular risk predictions: a Bayesian survival analysis

BackgroundCardiovascular disease (CVD) risk scores provide point estimates of individual risk without uncertainty quantification. The objective of the current study was to demonstrate the feasibility and clinical utility of calculating uncertainty surrounding individual CVD-risk predictions using Bayesian methods. Study Design and SettingIndividuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort—Secondary Manifestations of ARTerial disease (UCC-SMART). In 8,355 individuals, followed for median of 8.2 years (IQR 4.2–12.5), a Bayesian Weibull model was derived to predict the 10-year risk of recurrent CVD events. ResultsModel coefficients and individual predictions from the Bayesian model were very similar to that of a traditional (‘frequentist’) model but the Bayesian model also predicted 95% credible intervals (CIs) surrounding individual risk estimates. The median width of the individual 95%CrI was 5.3% (IQR 3.6–6.5) and 17% of the population had a 95%CrI width of 10% or greater. The uncertainty decreased with increasing sample size used for derivation of the model. Combining the Bayesian Weibull model with sampled hazard ratios based on trial reports may be used to estimate individual estimates of absolute risk reduction with uncertainty measures and the probability that a treatment option will result in a clinically relevant risk reduction. ConclusionEstimating uncertainty surrounding individual CVD risk predictions using Bayesian methods is feasible. The uncertainty regarding individual risk predictions could have several applications in clinical practice, like the comparison of different treatment options or by calculating the probability of the individual risk being below a certain treatment threshold. However, as the individual uncertainty measures only reflect sampling error and no biases in risk prediction, physicians should be familiar with the interpretation before widespread clinical adaption.

Performance of the Brazilian Fracture Assessment Risk Tool (FRAX) model and the age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines on fracture prediction in community-dwelling older adults: the São Paulo Ageing and Health (SPAH) Study.

To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

Predicting the probability of osteoporotic fracture risk in men versus women: do we need specific reference interventional thresholds for men?

BackgroundGender differences in the diagnosis and treatment of osteoporosis is a relatively common phenomenon, particularly amongst those patients under 80 years of age presenting with fragility fractures. The clinical implications of these findings are that strategies, which tend to focus on osteoporosis management in women, should also pay enough attention to osteoporosis in men. However, there have been questions whether there is a gender difference when setting intervention thresholds for osteoporosis management. This work was carried out aiming to determine the fracture probabilities calculated by FRAX at which therapeutic intervention in older men and women can be considered.ResultsAssessment of fracture risk probability thresholds in men revealed that for hip fractures, ROC was 0.754 (95% CI: 0.69–0.817). The sensitivity was 80.5% for threshold probabilities of 2.5%. For the major osteoporosis fracture, ROC was 0.828 (95% CI: 0.694–0.963). The sensitivity was 87.5% for threshold probabilities of 10%. Assessment of fracture risk probability threshold in women ROC was 0.760 (95% CI: 0.691–0.83). The sensitivity was 76.1% for threshold probabilities of 3%. For major osteoporosis fracture, ROC was 0.848 (95% CI: 0.784–0.912). The sensitivity was 87.3% for threshold probabilities of 15%.ConclusionOperational aspects of osteoporosis management should consider gender specific fracture thresholds. Interventional thresholds were found to be different in men compared to women. This helps to optimise fracture prevention in older men.