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Objective: To establish proof‐of‐concept for the dynamic prediction of adverse pregnancy outcome in women with a history of stillbirth or perinatal death, repeatedly throughout the pregnancy. Methods: A retrospective cohort study of women in a subsequent pregnancy following previous perinatal loss, who received antenatal care at a tertiary hospital between January 2014 and December 2017, was used as the basis for exploratory prognostic model development. Models were developed to repeatedly predict a composite adverse outcome (stillbirth or neonatal death, 5‐min Apgar score < 7, umbilical artery pH ≤ 7.05, admission to the neonatal intensive care unit for longer than 24 h, preterm birth (< 37 completed weeks) or birth weight < 10th centile) using the findings of sequential ultrasound scans for fetal biometry and umbilical and uterine artery Doppler. Results: In total, 506 participants were eligible, of whom 504 were included in the analysis. An adverse pregnancy outcome was experienced by 110 (22%) participants. The ability to predict the composite outcome using repeated head circumference and estimated fetal weight measurements improved as the pregnancy progressed (e.g. area under the receiver‐operating‐characteristics curve improved from 0.59 at 24 weeks' gestation to 0.74 at 36 weeks' gestation), supporting proof‐of‐concept. Predictors to include in dynamic prediction models were identified, including ultrasound measurements of fetal biometry, umbilical and uterine artery Doppler and placental size and shape. Conclusion: The present study supports proof‐of‐concept for dynamic prediction of adverse outcome in pregnancy following prior stillbirth or perinatal death, which could be used to identify risks earlier in pregnancy, while highlighting methodological challenges and requirements for subsequent large‐scale model development studies. © 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. [ABSTRACT FROM AUTHOR]

Objectives: Knee osteoarthritis (OA) is thought to be a slowly evolving disease with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years with evidence that over 6 months change in cartilage is not detectable. In contrast to cartilage, bone has the capacity to adapt rapidly, such as after fracture. We tested whether bone marrow lesions (BMLs) change in volume in 6 and 12 weeks, suggesting they may provide evidence of short term fluctuations of joint damage.Methods: In 62 patients with patellofemoral knee OA (mean age 55.7 years, 59.7% women, mean BMI 31.0), we obtained baseline, 6 and 12 week knee MRIs with contrast enhancement. Of those with BMLs at baseline, we assessed BML volume on the axial proton density fat saturated (FS) images and postcontrast sagittal T1 weighted FS images. We manually segmented BML volumes, testing repeatability of BML volumes in knees remeasured. Using the standard deviation of the difference between repeated measurements to calculate Bland-Altman Limits of Agreement, we determined how much BML volume change represented a change greater than due to chance.Results: Fifty-two patients had BMLs at baseline. Test-retest reliability for BML volume was high (ICC 0.89, 95% CI 0.80-0.97). All knees showed at least some change in BML volume by 6 and 12 weeks. On the axial view at 6 weeks, 20/49 (40.8%) knees showed BML volume changes greater than the limits of agreement with similar results at 12 weeks. BML changes were evenly divided among knees with enlarging and shrinking BMLs. 63.3% of the knees had more than 50% change in BML volume at either 6 or 12 weeks on the axial view and 48.7% on the sagittal view.Conclusions: Knee BML volumes change in several weeks in many persons with knee OA. To the extent that they could be regarded as treatment targets, trials testing BML effects could avoid the usual prolonged structure modification trials. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer radiotherapy is increasingly delivered supine with multiple, short breath-holds. There may be heart and lung sparing advantages for locoregional breast cancer of both prone treatment and in a single breath-hold. We test here whether single prolonged breath-holds are possible in the prone, front crawl position., Methods: 19 healthy volunteers were trained to deliver supine, single prolonged breath-holds with pre-oxygenation and hypocapnia. We tested whether all could achieve the same durations in the prone, front crawl position., Results: 19 healthy volunteers achieved supine, single prolonged breath-holds for mean of 6.2 ± 0.3 min. All were able to hold safely for the same duration while prone (6.1 ± 0.2 min ns . by paired ANOVA). With prone, the increased weight on the chest did not impede chest inflation, nor the ability to hold air in the chest. Thus, the rate of chest deflation (mean anteroposterior deflation movement of three craniocaudally arranged surface markers on the spinal cord) was the same (1.2 ± 0.2, 2.0 ± 0.4 and 1.2 ± 0.4 mm/min) as found previously during supine prolonged breath-holds. No leakage of carbon dioxide or air was detectable into the facemask., Conclusion: Single prolonged (>5 min) breath-holds are equally possible in the prone, front crawl position., Advances in Knowledge: Prolonged breath-holds in the front crawl position are possible and have the same durations as in the supine position. Such training would therefore be feasible for some patients with breast cancer requiring loco-regional irradiation. It would have obvious advantages for hypofractionation.

Objective: Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA., Method: Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N = 50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms., Results: There was no association between knee pain and total subchondral BML volume (b = 0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b = 1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b = 0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b = 51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b = 2.2, 95% CI 0.6 to 3.7)., Conclusion: The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: International guidelines recommend intra-articular steroid injections (IASIs) in the management of hip osteoarthritis (OA), though these recommendations are extrapolated primarily from studies of knee OA. The aim of this systematic review was to assess the efficacy of IASI on pain in hip OA., Methods: MEDLINE, EMBASE, AMED, CINAHL Plus, Web of Science and the Cochrane Central Register of Controlled Trials were searched to May 2015. Randomised controlled trials (RCTs) assessing the efficacy of hip IASI on pain were included. Pre-specified data was extracted using a standardised form. Quality was assessed using the Jadad score., Results: Five trials met the inclusion criteria. All had a small number of participants (≤101). All studies reported some reduction in pain at 3-4 weeks post-injection compared to control. Based on data from individual trials the treatment effect size was large at 1 week post-injection but declined thereafter. A significant (moderate effect size) reduction in pain was reported in two trials up to 8 weeks following IASI. Pooled results of two trials (n = 90) showed an increased likelihood of meeting the Outcome measures in Rheumatology Clinical Trials (OMERACT)-Osteoarthritis Research Society International (OARSI) response criteria at 8 weeks post-IASI, odds ratio 7.8 (95% confidence interval (CI): 2.7-22.8). The number needed to treat to achieve one OMERACT-OARSI responder at 8 weeks post-injection was 2.4 (95% CI: 1.7-4.2). Hip IASI appear to be generally well tolerated., Conclusions: Hip IASI may be efficacious in short-term pain reduction in those with hip OA though the quality of the evidence was relatively poor. Further large, methodologically rigorous trials are required to verify whether intra-articular corticosteroids are beneficial and for how long., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Synovium is increasingly a target of osteoarthritis (OA) treatment, yet its optimal measurement is unclear. Using dynamic contrast enhanced (DCE) MRI in knee OA patients before and after intraarticular steroid injection, we compared the responsiveness of static synovial volume measures to measures of dynamic changes in synovial enhancement, changes that are strongly related to synovial vascularity., Methods: Ninety three patients underwent DCE-MRI before and 1-2 weeks after intra-articular injection of 80 mg methylprednisolone. Synovium was segmented and volume, relative enhancement rate (RER), maximum relative enhancement (REmax), late relative enhancement (RElate) and pharmacokinetic parameters (K(trans), ve) were calculated. KOOS (​knee injury and osteoarthritis outcome score) pain score was recorded before and after injection. Standardized change scores were calculated for each parameter. Linear regression and Pearson's correlations were used to investigate the relationship between change in MRI parameters and change in pain., Results: The change in standardized score for the measures of synovial enhancement, RElate and REmax were -0.58 (95% CI -0.79 to -0.37) and -0.62 (95% CI -0.83 to -0.41) respectively, whereas the score for synovial volume was -0.30 (-0.52 to -0.09). Further, change in knee pain correlated more strongly with changes in enhancement (for both REmax and RElate, r = -0.27 (95% CI -0.45 to -0.07)) than with changes in synovial volume -0.15 (-0.35 to 0.05)., Conclusion: This study suggests DCE-MRI derived measures of synovial enhancement may be more sensitive to the response to treatment and more strongly associated with changes in pain than synovial volume and may be better outcomes for assessment of structural effects of treatment in OA., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Lateral wedge insoles are a potential simple treatment for medial knee osteoarthritis (OA) patients by reducing the external knee adduction moment (EKAM). However in some patients, an increase in their EKAM is seen. Understanding the role of the ankle joint complex in the response to lateral wedge insoles is critical in understanding and potentially identifying why some patients respond differently to lateral wedge insoles., Method: Participants with medial tibiofemoral OA underwent gait analysis whilst walking in a control shoe and a lateral wedge insole. We evaluated if dynamic ankle joint complex coronal plane biomechanical measures could explain and identify those participants that increased (biomechanical non-responder) or decreased (biomechanical responder) EKAM under lateral wedge conditions compared to the control shoe., Results: Of the 70 participants studied (43 male), 33% increased their EKAM and 67% decreased their EKAM. Overall, lateral wedge insoles shifted the centre of foot pressure laterally, increased eversion of the ankle/subtalar joint complex (STJ) and the eversion moment compared to the control condition. Ankle angle at peak EKAM and peak eversion ankle/STJ complex angle in the control condition predicted if individuals were likely to decrease EKAM under lateral wedge conditions., Conclusions: Coronal plane ankle/STJ complex biomechanical measures play a key role in reducing EKAM when wearing lateral wedge insoles. These findings may assist in the identification of those individuals that could benefit more from wearing lateral wedge insoles., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Arthrogenous muscle inhibition (AMI) is thought to contribute to quadriceps weakness in knee osteoarthritis (OA), but its relationship with structural changes of bone marrow lesions (BMLs), capsular distension and pain is unclear. This study's objective was to investigate the factors associated with AMI in subjects with symptomatic patellofemoral joint OA (PFJOA)., Design: 126 Subjects with predominant PFJOA were assessed for pain by the visual analogue scale (VAS) for a nominated aggravating activity. Their more symptomatic knee underwent a magnetic resonance imaging (MRI) scan which was used to assess BMLs and synovitis which were scored using the Whole Organ MRI score (WORMS). Quadriceps AMI was measured by calculating the activation deficit and quadriceps strength assessed by isometric maximum voluntary contraction. Multiple linear regressions were used to assess factors associated with AMI., Results: We studied 124 subjects [mean age 55.5 (SD 7.5); 57.14% female]. In regression analyses, higher levels of AMI were significantly associated with more severe knee pain and with lower BML score., Conclusion: Quadriceps AMI in knee OA is associated with severity of knee pain and surprisingly with lower BML scores., (Copyright © 2014. Published by Elsevier Ltd.)

The precise contribution of the CO2-dependent respiratory rhythm to sinus arrhythmia in eupnea is unclear. The respiratory rhythm and sinus arrhythmia were measured in 12 normal, unanesthetized subjects in normocapnia and hypocapnia during mechanical hyperventilation with positive pressure. In normocapnia (41 +/- 1 mmHg), the respiratory rhythm was always detectable from airway pressure and inspiratory electromyogram activity. The amplitude of sinus arrhythmia (138 +/- 21 ms) during mechanical hyperventilation with positive pressure was not significantly different from that in eupnea. During the same mechanical hyperventilation pattern but in hypocapnia (24 +/- 1 mmHg), the respiratory rhythm was undetectable and the amplitude of sinus arrhythmia was significantly reduced (to 40 +/- 5 ms). These results show a greater contribution to sinus arrhythmia from the respiratory rhythm during hypocapnia caused by mechanical hyperventilation than previously indicated in normal subjects during hypocapnia caused by voluntary hyperventilation. We discuss whether the respiratory rhythm provides the principal contribution to sinus arrhythmia in eupnea.

A substantial portion of sinus arrhythmia in conscious humans appears to be caused by the CO2-dependent central respiratory rhythm. Under some circumstances, therefore, sinus arrhythmia might indicate the presence of the central respiratory rhythm. Humans can voluntarily modify their central respiratory rhythm (e.g., by pacing breathing or by delaying or advancing breaths), but it is not clear what happens to it from the start of breath holding. In this study, we show that sinus arrhythmia persists from the start of breath holds prolonged by preoxygenation. We also show that some of the frequency components of sinus arrhythmia start within each subject's eupneic frequency range and change when end-tidal Pco2 is lowered or raised, as we would expect if the central respiratory rhythm continues from the start of breath holding. We discuss whether sinus arrhythmia can indicate if the central respiratory rhythm continues from the start of breath holding.

Objective: The etiology of oligohydramnios-related pulmonary hypoplasia is not understood but is known to involve chronic lung liquid loss. We tested the hypothesis that low amniotic pressure in oligohydramnios disturbs the normal tracheal-amniotic pressure gradient to increase lung liquid loss and impair lung development., Study Design: Chronic pharyngeal catheterization with drainage to the exterior was used in 15 fetal sheep to mimic reduced amniotic pressure at the upper airway in the presence of normal amniotic fluid volume., Results: Pharyngeal pressures relative to amniotic pressures were negative in all drained fetuses (mean +/- SE -3.0 +/- 0.6 mm Hg), in contrast to positive pressures in controls (0.7 +/- 0.1 mm Hg). There was no significant difference in lung weight or deoxyribonucleic acid relative to body weight, or in lung morphometry, between 10 fetuses drained for 10 to 21 days and their control cotwins., Conclusion: Mimicking low amniotic pressure in the upper airway by chronic fetal pharyngeal drainage does not impair lung development in fetal sheep.

To investigate the recent suggestion that fetal hypoxemia and acidemia in polyhydramnios are secondary to raised amniotic pressure, 5 to 15 L of normal saline solution was infused intraamniotically at 100 ml/min in seven ewes. Amniotic pressure increased linearly by 1.0 +/- 0.013 (mean +/- SEM) mm Hg per liter infused. Infusion of 15 L produced a mean rise in amniotic pressure of 15.2 +/- 1.2 mm Hg (p less than 0.001) but no significant change in fetal pH, PCO2, PO2, fetal heart rate, or mean arterial pressure. A similar rise in amniotic pressure and lack of change in blood gas values occurred in two control ewes infused intraperitoneally. Rupture of the membranes occurred in two of three amnioinfusions of 15 L. We conclude that acute amnioinfusion raises amniotic pressure in sheep but does not alter fetal blood gas status.

The mechanism of oligohydramnios-related pulmonary hypoplasia (PH) is not understood, but is known to involve chronic loss of lung liquid. In order to investigate the recent suggestion that fetal breathing movements are absent or diminished in oligohydramnios-related PH, we made continuous recordings of fetal breathing movements (FBM) during chronic lung drainage in tracheostomized fetal sheep. FBM remained present throughout the drainage period. There was no significant difference in the number or duration of FBM epochs in tracheostomized fetuses compared to controls, although there was a slight reduction in incidence between 126 and 133 days (P = 0.02). PH in the fetuses undergoing chronic lung liquid drainage was confirmed by significant reductions in lung weight, volume, DNA, and total airspace, and in altered maturation. This study is consistent with other data suggesting that inhibition of FBM is not the primary mechanism of oligohydramnios-related pulmonary hypoplasia.

We measured the effects of 2 minutes of vibroacoustic stimulation on the activity of unanesthetized fetal sheep in utero. We were unable to detect any changes in activity after stimulation with a model 5C electrolarynx. With more powerful stimulation using a mechanical oscillator, fetal electrocortical activity desynchronized. Fetal breathing and eye movements changed with electrocortical activity and there was an increase in nuchal muscle activity. Stimulation caused a small decrease in fetal heart rate. Responses to stimulation were not seen in four of the five fetuses with bilateral cochlear ablation. These results indicate that in fetal sheep the auditory apparatus is necessary for the detection of vibroacoustic stimuli. The difference in responsiveness of the sheep and human fetus appears to be because of a difference in central processing after detection of the stimulus.