Addition of specific types of alginates to drinks can enhance postmeal suppression of hunger, by forming strong gastric gels in the presence of calcium. However, some recent studies have not ...demonstrated an effect of alginate/calcium on appetite, perhaps because the selected alginates do not produce sufficiently strong gels or because the alginates were not sufficiently hydrated when consumed. Therefore, the objective of the study was to test effects on appetite of a strongly gelling and fully hydrated alginate in an acceptable, low‐viscosity drink formulation. In a balanced order crossover design, 23 volunteers consumed a meal replacement drink containing protein and calcium and either 0 (control), 0.6, or 0.8% of a specific high‐guluronate alginate. Appetite (six self‐report scales) was measured for 5 h postconsumption. Relevant physicochemical properties of the drinks were measured, i.e., product viscosity and strength of gel formed under simulated gastric conditions. Hunger was robustly reduced (20–30% lower area under the curve) with 0.8% alginate (P < 0.001, analysis of covariance), an effect consistent across all appetite scales. Most effects were also significant with 0.6% alginate, and a clear dose‐response observed. Gastric gel strength was 1.8 and 3.8 N for the 0.6 and 0.8% alginate drinks, respectively, while product viscosity was acceptable (<0.5 Pa·s at 10 s−1). We conclude that strongly gastric‐gelling alginates at relatively low concentrations in a low‐viscosity drink formulation produced a robust reduction in hunger responses. This and other related studies indicate that the specific alginate source and product matrix critically impacts upon apparent efficacy.
Pain is common in patients with cancer. The World Health Organisation recommends paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and combined with other agents for ...moderate/severe pain. This study estimated associations of NSAIDs with recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and the incidence of immune-related adverse events (irAEs) in high-risk patients with resected melanoma in the EORTC 1325/KEYNOTE-054 phase III clinical trial.
Patients with AJCC7 stage IIIA, IIIB or IIIC resected melanoma were randomized to receive 200 mg of adjuvant pembrolizumab (N = 514) or placebo (N = 505) 3-weekly for one year or until recurrence. As previously reported, pembrolizumab prolonged RFS and DMFS. NSAID use was defined as administration between 7 days pre-randomization and starting treatment. Multivariable Cox and Fine and Gray models were used to estimate hazard ratios (HRs) for associations of NSAIDs with RFS, DMFS and irAEs.
Of 1019 patients randomized, 59 and 44 patients in the pembrolizumab and placebo arms, respectively, used NSAIDs. NSAIDs were not associated with RFS (HR 0.91, 95% CI 0.58–1.43) or DMFS in the pembrolizumab (HR 1.03, 95% CI 0.65–1.66) or placebo arms (for RFS, HR 0.76, 95% CI 0.48–1.20; for DMFS, HR 0.80, 95% CI 0.49–1.31). NSAIDs were associated with the incidence of irAEs in the placebo arm (HR 3.06, 95% CI 1.45–6.45) but not in the pembrolizumab arm (HR 0.94, 95% CI 0.58–1.53).
NSAIDs were not associated with efficacy outcomes nor the risk of irAEs in patients with resected high-risk stage III melanoma receiving adjuvant pembrolizumab.
•NSAIDs were not associated with recurrence-free survival.•NSAIDs were not associated with distant metastasis-free survival.•NSAIDs were not associated with the incidence of immune-related adverse events.
OBJECTIVETo explore clinical outcomes in older adults with acute ischemic stroke treated with endovascular thrombectomy (EVT).
METHODSWe included consecutive patients (2014–2016) with an anterior ...circulation occlusion undergoing EVT from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry. We assessed the effect of age (dichotomized at ≥80 years and as continuous variable) on the modified Rankin Scale (mRS) score at 90 days, symptomatic intracranial hemorrhage (sICH), and reperfusion rate. The association between age and mRS was assessed with multivariable ordinal logistic regression, and a multiplicative interaction term was added to the model to assess modification of reperfusion by age on outcome.
RESULTSOf the 1,526 patients, 380 (25%) were ≥80 years of age (referred to here as older adults). Older adults had a worse functional outcome than younger patients (adjusted common odds ratio acOR for an mRS score shift toward better outcome 0.31, 95% confidence interval CI 0.24–0.39). Mortality was also higher in older adults (51% vs 22%, adjusted odds ratio 3.12, 95% CI 2.33–4.19). There were no differences in proportion of patients with mRS scores of 4 to 5, sICH, or reperfusion rates. Successful reperfusion was more strongly associated with a shift toward good functional outcome in older adults than in younger patients (acOR 3.22, 95% CI 2.04–5.10 vs 2.00, 95% CI 1.56–2.57, pinteraction = 0.026).
CONCLUSIONOlder age is associated with an increased absolute risk of poor clinical outcome, while the relative benefit of successful reperfusion seems to be higher in these patients. These results should be taken into consideration in the selection of older adults for EVT.
Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may ...increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome.
Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume.
Patients with Δ≥10.9 HU (n=81 44%) and ε≥6.5% (n=77 42%) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Δ and -0.40 for ε).
This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.
Various statistical approaches can be used to deal with unmeasured confounding when estimating treatment effects in observational studies, each with its own pros and cons. This study aimed to compare ...treatment effects as estimated by different statistical approaches for two interventions in observational stroke care data.
We used prospectively collected data from the MR CLEAN registry including all patients (n = 3279) with ischemic stroke who underwent endovascular treatment (EVT) from 2014 to 2017 in 17 Dutch hospitals. Treatment effects of two interventions - i.e., receiving an intravenous thrombolytic (IVT) and undergoing general anesthesia (GA) before EVT - on good functional outcome (modified Rankin Scale ≤2) were estimated. We used three statistical regression-based approaches that vary in assumptions regarding the source of unmeasured confounding: individual-level (two subtypes), ecological, and instrumental variable analyses. In the latter, the preference for using the interventions in each hospital was used as an instrument.
Use of IVT (range 66-87%) and GA (range 0-93%) varied substantially between hospitals. For IVT, the individual-level (OR ~ 1.33) resulted in significant positive effect estimates whereas in instrumental variable analysis no significant treatment effect was found (OR 1.11; 95% CI 0.58-1.56). The ecological analysis indicated no statistically significant different likelihood (β = - 0.002%; P = 0.99) of good functional outcome at hospitals using IVT 1% more frequently. For GA, we found non-significant opposite directions of points estimates the treatment effect in the individual-level (ORs ~ 0.60) versus the instrumental variable approach (OR = 1.04). The ecological analysis also resulted in a non-significant negative association (0.03% lower probability).
Both magnitude and direction of the estimated treatment effects for both interventions depend strongly on the statistical approach and thus on the source of (unmeasured) confounding. These issues should be understood concerning the specific characteristics of data, before applying an approach and interpreting the results. Instrumental variable analysis might be considered when unobserved confounding and practice variation is expected in observational multicenter studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND AND PURPOSE—If a relationship between stroke etiology and thrombus computed tomography characteristics exists, assessing these characteristics in clinical practice could serve as a useful ...additional diagnostic tool for the identification of stroke subtype. Our purpose was to study the association of stroke etiology and thrombus computed tomography characteristics in patients with acute ischemic stroke due to a large vessel occlusion.
METHODS—For 1429 consecutive patients enrolled in the MR CLEAN Registry, we determined stroke cause as defined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria. The association of stroke etiology with the hyperdense artery sign, clot burden score, and thrombus location was estimated with univariable and multivariable binary and ordinal logistic regression. Additionally, for 367 patients with available thin-section imaging, we assessed the association of stroke etiology with absolute and relative thrombus attenuation, distance from internal carotid artery-terminus to thrombus, thrombus length, and thrombus attenuation increase with univariable and multivariable linear regression.
RESULTS—Compared with cardioembolic strokes, noncardioembolic strokes were associated with presence of hyperdense artery sign (odds ratio, 2.2 95% CI, 1.6–3.0), lower clot burden score (common odds ratio, 0.4 95% CI, 0.3–0.6), shift towards a more proximal thrombus location (common odds ratio, 0.2 95% CI, 0.2–0.3), higher absolute thrombus attenuation (β, 3.6 95% CI, 0.9–6.4), decrease in distance from the ICA-terminus (β, −5.7 95% CI, −8.3 to −3.0), and longer thrombi (β, 8.6 95% CI, 6.5−10.7), based on univariable analysis. Thrombus characteristics of strokes with undetermined cause were similar to those of cardioembolic strokes.
CONCLUSIONS—Thrombus computed tomography characteristics of cardioembolic stroke are distinct from those of noncardioembolic stroke. Additionally, our study supports the general hypothesis that many cryptogenic strokes have a cardioembolic cause. Further research should focus on the use of thrombus computed tomography characteristics as a diagnostic tool for stroke cause in clinical practice.
Abstract
Background
Between-center variation in outcome may offer opportunities to identify variation in quality of care. By intervening on these quality differences, patient outcomes may be ...improved. However, whether observed differences in outcome reflect the true quality improvement potential is not known for many diseases. Therefore, we aimed to analyze the effect of differences in performance on structure and processes of care, and case-mix on between-center differences in outcome after endovascular treatment (EVT) for ischemic stroke.
Methods
In this observational cohort study, ischemic stroke patients who received EVT between 2014 and 2017 in all 17 Dutch EVT-centers were included. Primary outcome was the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death), at 90 days. We used random effect proportional odds regression modelling, to analyze the effect of differences in structure indicators (center volume and year of admission), process indicators (time to treatment and use of general anesthesia) and case-mix, by tracking changes in
tau
2
, which represents the amount of between-center variation in outcome.
Results
Three thousand two hundred seventy-nine patients were included. Performance on structure and process indicators varied significantly between EVT-centers (
P
< 0.001). Predicted probability of good functional outcome (modified Rankin Scale 0–2 at 90 days), which can be interpreted as an overall measure of a center’s case-mix, varied significantly between 17 and 50% across centers. The amount of between-center variation (
tau
2
) was estimated at 0.040 in a model only accounting for random variation. This estimate more than doubled after adding case-mix variables (
tau
2
: 0.086) to the model, while a small amount of between-center variation was explained by variation in performance on structure and process indicators (
tau
2
: 0.081 and 0.089, respectively). This indicates that variation in case-mix affects the differences in outcome to a much larger extent.
Conclusions
Between-center variation in outcome of ischemic stroke patients mostly reflects differences in case-mix, rather than differences in structure or process of care. Since the latter two capture the real quality improvement potential, these should be used as indicators for comparing center performance. Especially when a strong association exists between those indicators and outcome, as is the case for time to treatment in ischemic stroke.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Endovascular treatment (EVT) is standard of care in anterior circulation large vessel occlusions. In posterior circulation occlusions, data on EVT in isolated posterior cerebral artery (PCA) ...occlusions are limited, although PCA occlusions can cause severe neurological deficit.
To describe in a prospective study the clinical manifestations, outcomes, and safety of EVT in isolated PCA occlusions.
We used data (2014-2017) from the MR CLEAN Registry, a nationwide, prospective cohort of EVT-treated patients in the Netherlands. We included patients with acute ischemic stroke (AIS) due to an isolated PCA occlusion on CT angiography. Patients with concurrent occlusion of the basilar artery were excluded. Outcomes included change in National Institutes of Health Stroke Scale (ΔNIHSS) score, modified Rankin Scale (mRS) score 0-3 after 90 days, mortality, expanded Thrombolysis in Cerebral Infarction (eTICI), and periprocedural complications.
Twenty (12%) of 162 patients with posterior circulation occlusions had an isolated PCA occlusion. Median age was 72 years; 13 (65%) were women. Median baseline NIHSS score was 13 (IQR 5-21). Six (30%) patients were comatose. Twelve patients (60%) received IVT. Median ΔNIHSS was -4 (IQR -11-+1). At follow-up, nine patients (45%) had mRS score 0-3. Seven (35%) died. eTICI 2b-3 was achieved in 13 patients (65%). Nine patients (45%) had periprocedural complications. No symptomatic intracranial hemorrhages (sICH) occurred.
EVT should be considered in selected patients with AIS with an isolated PCA occlusion, presenting with moderate-severe neurological deficits, as EVT was technically feasible in most of our patients and about half had good clinical outcome. In case of lower NIHSS score, a more conservative approach seems warranted, since periprocedural complications are not uncommon. Nonetheless, EVT seems reasonably safe considering the absence of sICH in our study.
Objective:
To compare in-depth speech results in Scandcleft Trial 1 as well as reference data from peers without cleft palate (CP).
Design:
A prospective randomized clinical trial.
Setting:
A Danish ...and a Swedish CP center.
Participants:
143 of 148 randomized 5-year-olds with unilateral cleft lip and palate. All received lip and velum closure at 4 months, and hard palate closure at 12 months (arm A) or 36 months (arm B).
Main Outcome Measures:
A composite measure based on velopharyngeal competence (VPC) or velopharyngeal incompetence (VPI), an overall assessment of VPC from connected speech (VPC-Rate), Percentage of Consonants Correct (PCC-score), and consonant errors. Speech therapy visits, average hearing thresholds, and secondary pharyngeal surgeries documented burden of treatment.
Results:
Across the trial, 61.5% demonstrated VPC and 38.5% VPI. Twenty-two percent of participants achieved age appropriate PCC-scores. There were no statistically significant differences between arms or centers for these measures. In the Danish center, arm B: achieved lower PCC-scores (P = .01); obtained PCC-scores without s-errors below 79% (P = .002); produced ≥3 active oral cleft speech characteristics (P = .004) than arm A. In both centers, arm B attended more speech visits.
Conclusions:
At age 5, differences between centers and treatment arms were not statistically significant for VPC/VPI, but consonant proficiency differed between treatment arms in the Danish center. Poor speech outcomes were seen for both treatment arms. Variations between centers were observed. As the Swedish center had few participants, intercenter comparisons should be interpreted with caution.
Abstract only Introduction: Rapid detection of a large vessel occlusion (LVO) in acute ischemic stroke is beneficial as it may accelerate therapeutic management. The hyperdense artery sign (HAS) on ...non-contrast CT (NCCT) is result of an acute thrombolytic occlusion and is known as the earliest radiological marker to identify LVO. However, HAS is not apparent for all LVOs and detection by a less-trained eye can be sub-optimal. Artificial intelligence (AI) may support the non-trained radiologist in swift and accurate LVO detection. We evaluated the LVO detection accuracy of AI, and compared this to human expert performance. Materials and Methods: We used a convolutional neural network (CNN) developed by Nico.lab (www.nico-lab.com) that automatically detects and segments thrombi on NCCT using a patch-based approach. The CNN was trained using thrombus and non-thrombus patches, combined with the contralateral side. In a retrospective analysis of thin-slice NCCTs, obtained from Amsterdam UMC patients, with (ICA-T, M1, or M2) and without occlusions (stroke mimics), the CNN and two observers (>15y and >4y of experience) assessed LVO-presence and location. Ground truth was established by consensus between two different experts with >5y of experience, using both CTA and NCCT. Thrombus segmentations were considered accurate if segmentations overlapped with the ground truth. Sensitivity and specificity of the LVO detection were assessed. Results: We included 107 patients, of which 59 had proven LVOs. Nico.lab CNN showed a thrombus segmentation accuracy of 81%, vs. 81% and 77% of human experts. Sensitivity of LVO detection by CNN was 0.86, vs. 0.95 and 0.79 for human observers. Specificity was 0.65 for the CNN vs. 0.58 and 0.82 for human experts respectively. Conclusion: AI-based LVO detection on NCCT showed comparable results to expert observers. This supportive tool could lead to earlier detection of LVO in acute stroke situations. Fig 1A. HAS; B. CNN output (red); C. clot on CTA (blue arrow)
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