60,345 research outputs found
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
Prognostic model for predicting survival in very preterm infants: an external validation study
No full textObjective: To perform a temporal and geographical validation of a prognostic model, considered of highest methodological quality in a recently published systematic review, for predicting survival in very preterm infants admitted to the neonatal intensive care unit. The original model was developed in the UK and included gestational age, birthweight and gender. Design: External validation study in a population-based cohort. Setting: Dutch neonatal wards. Population or sample: All admitted white, singleton infants born between 23+0 and 32+6 weeks of gestation between 1 January 2015 and 31 December 2019. Additionally, the model’s performance was assessed in four populations of admitted infants born between 24+0 and 31+6 weeks of gestation: white singletons, non-white singletons, all singletons and all multiples. Methods: The original model was applied in all five validation sets. Model performance was assessed in terms of calibration and discrimination and, if indicated, it was updated. Main outcome measures: Calibration (calibration-in-the-large and calibration slope) and discrimination (c statistic). Results: Out of 6092 infants, 5659 (92.9%) survived. The model showed good external validity as indicated by good discrimination (c statistic 0.82, 95% CI 0.79–0.84) and calibration (calibration-in-the-large 0.003, calibration slope 0.92, 95% CI 0.84–1.00). The model also showed good external validity in the other singleton populations, but required a small intercept update in the multiples population. Conclusions: A high-quality prognostic model predicting survival in very preterm infants had good external validity in an independent, nationwide cohort. The accurate performance of the model indicates that after impact assessment, implementation of the model in clinical practice in the neonatal intensive care unit could be considered. Tweetable abstract: A high-quality model predicting survival in very preterm infants is externally valid in an independent cohort
Boosting BOLD fMRI by K-Space density weighted echo planar imaging
No full textFunctional magnetic resonance imaging (fMRI) has become a powerful and influential method to non-invasively study neuronal brain activity. For this purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used. T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI acquisition technique. Here, we present an alternative to its standard Cartesian recordings, i.e. k-space density weighted EPI, which is expected to increase the signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot measurements, we show that fMRI by k-space density weighted EPI is feasible and that this new acquisition technique in fact boosted spatial and temporal SNR as well as the detection of local fMRI activations. Spatial resolution, spatial response function and echo time were identical for density weighted and conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting can improve activation detection and has the potential to further increase the sensitivity of fMRI investigations
Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study)
No full textBACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO 2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO 2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924
Effect of physical exercise on the hippocampus and global grey matter volume in breast cancer patients: A randomized controlled trial (PAM study)
No full textBACKGROUND: Physical exercise in cancer patients is a promising intervention to improve cognition and increase brain volume, including hippocampal volume. We investigated whether a 6-month exercise intervention primarily impacts total hippocampal volume and additionally hippocampal subfield volumes, cortical thickness and grey matter volume in previously physically inactive breast cancer patients. Furthermore, we evaluated associations with verbal memory. METHODS: Chemotherapy-exposed breast cancer patients (stage I-III, 2-4 years post diagnosis) with cognitive problems were included and randomized in an exercise intervention (n = 70, age = 52.5 ± 9.0 years) or control group (n = 72, age = 53.2 ± 8.6 years). The intervention consisted of 2x1 hours/week of supervised aerobic and strength training and 2x1 hours/week Nordic or power walking. At baseline and at 6-month follow-up, volumetric brain measures were derived from 3D T1-weighted 3T magnetic resonance imaging scans, including hippocampal (subfield) volume (FreeSurfer), cortical thickness (CAT12), and grey matter volume (voxel-based morphometry CAT12). Physical fitness was measured with a cardiopulmonary exercise test. Memory functioning was measured with the Hopkins Verbal Learning Test-Revised (HVLT-R total recall) and Wordlist Learning of an online cognitive test battery, the Amsterdam Cognition Scan (ACS Wordlist Learning). An explorative analysis was conducted in highly fatigued patients (score of ≥ 39 on the symptom scale 'fatigue' of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire), as previous research in this dataset has shown that the intervention improved cognition only in these patients. RESULTS: Multiple regression analyses and voxel-based morphometry revealed no significant intervention effects on brain volume, although at baseline increased physical fitness was significantly related to larger brain volume (e.g., total hippocampal volume: R = 0.32, B = 21.7 mm 3, 95 % CI = 3.0 - 40.4). Subgroup analyses showed an intervention effect in highly fatigued patients. Unexpectedly, these patients had significant reductions in hippocampal volume, compared to the control group (e.g., total hippocampal volume: B = -52.3 mm 3, 95 % CI = -100.3 - -4.4)), which was related to improved memory functioning (HVLT-R total recall: B = -0.022, 95 % CI = -0.039 - -0.005; ACS Wordlist Learning: B = -0.039, 95 % CI = -0.062 - -0.015). CONCLUSIONS: No exercise intervention effects were found on hippocampal volume, hippocampal subfield volumes, cortical thickness or grey matter volume for the entire intervention group. Contrary to what we expected, in highly fatigued patients a reduction in hippocampal volume was found after the intervention, which was related to improved memory functioning. These results suggest that physical fitness may benefit cognition in specific groups and stress the importance of further research into the biological basis of this finding
Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT)
No full textIntroduction A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test—called the Genital InFlammation Test (GIFT)—for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. Methods and analysis We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical (‘diagnostic study’) and a qualitative, modelling and economic (‘an integration into care study’) part. The diagnostic study aims to evaluate GIFT’s performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. Ethics and dissemination Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications. The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d’Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046). Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484)
Hippocampal sulcal cavities prevalence, risk factors and association with cognitive performance. The SMART-Medea study and PREDICT-MR study
No full textHippocampal sulcal cavities (HSCs) are frequently observed on MRI, but their etiology and relevance is unclear. HSCs may be anatomical variations, or result from pathology. We assessed the presence of HSCs, and their cross-sectional association with demographics, vascular risk factors and cognitive functioning in two study samples. Within a random sample of 92 patients with vascular disease from the SMART-Medea study (mean age = 62, SD = 9 years) and 83 primary care patients from the PREDICT-MR study (mean age = 62, SD = 12 years) one rater manually scored HSCs at 1.5 T 3D T1-weighted coronal images blind to patient information. We estimated relative risks of age, sex and vascular risk factors with presence of HSCs using Poisson regression with log-link function and robust standard errors adjusted for age and sex. Using ANCOVA adjusted for age, sex, and education we estimated the association of the number of HSCs with memory, executive functioning, speed, and working memory. In the SMART-Medea study HSCs were present in 65% and in 52% in the PREDICT-MR study (χ2 = 2.99, df = 1, p = 0.08). In both samples, no significant associations were observed between presence of HSCs and age (SMART-Medea: RR = 1.00; 95%CI 0.98-1.01; PREDICT-MR: RR = 1.01; 95%CI 0.99-1.03), sex, or vascular risk factors. Also, no associations between HSCs and cognitive functioning were found in either sample. HSCs are frequently observed on 1.5 T MRI. Our findings suggest that, in patients with a history of vascular disease and primary care attendees, HSCs are part of normal anatomic variation of the human hippocampus rather than markers of pathology
Effect of Physical Exercise on MRI-Assessed Brain Perfusion in Chemotherapy-Treated Breast Cancer Patients: A Randomized Controlled Trial
No full textBACKGROUND: Exercise is a promising intervention to alleviate cognitive problems in breast cancer patients, but studies on mechanisms underlying these effects are lacking. PURPOSE: Investigating whether an exercise intervention can affect cerebral blood flow (CBF) in cognitively impaired breast cancer patients and to determine if CBF changes relate to memory function. STUDY TYPE: Prospective. POPULATION: A total of 181 chemotherapy-treated stage I-III breast cancer patients with cognitive problems and relatively low physical activity levels (≤150 minutes moderate to vigorous physical activity per week), divided into an exercise (N = 91) or control group (N = 90). FIELD STRENGTH/SEQUENCE: Two-dimensional echo planar pseudo-continuous arterial spin labeling CBF sequence at 3 T. ASSESSMENT: The 6-month long intervention consisted of (supervised) aerobic and strength training, 4 × 1 hour/week. Measurements at baseline (2-4 years post-diagnosis) and after 6 months included gray matter CBF in the whole brain, hippocampus, anterior cingulate cortex, and posterior cingulate cortex. Physical fitness and memory function were also assessed. Subgroup analyses were performed in patients with high fatigue levels at baseline. STATISTICAL TESTS: Multiple regression analyses with a two-sided alpha of 0.05 for all analyses. RESULTS: There was a significant improvement in physical fitness (VO 2peak in mL/minute/kg) in the intervention group (N = 53) compared to controls (N = 51, β = 1.47 mL/minute/kg, 95% CI: 0.44-2.50). However, no intervention effects on CBF were found (eg, whole brain: P = 0.565). Highly fatigued patients showed larger but insignificant treatment effects on CBF (eg, whole brain: P = 0.098). Additionally, irrespective of group, a change in physical fitness was positively associated with changes in CBF (eg, whole brain: β = 0.75, 95% CI: 0.07-1.43). There was no significant relation between CBF changes and changes in memory performance. DATA CONCLUSION: The exercise intervention did not affect CBF of cognitively affected breast cancer patients. A change in physical fitness was associated with changes in CBF, but changes in CBF were not associated with memory functioning. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 5
All repair and reconstruction. Techniques from the SANTI study group
No full textBackground: Combining an anterior cruciate ligament (ACL) reconstruction with an anterolateral ligament (ALL) reconstruction results in significant advantages including reduced graft rupture rates, a lower risk of reoperation for secondary meniscectomy, improved knee stability, and higher rates of return to preinjury levels of sport. Indications: The previously reported indications for combined ACL and ALL reconstruction are as follows: ACL reconstruction revision; high-grade pivot shift test; long-term ACL rupture; young patients; pivoting activities; concomitant medial meniscus repair, and, specifically, regarding the ALL repair, it must be an acute surgery (within 15 days from injury). Technique Description: Several modern techniques have been described to repair and reconstruct the ALL. This technical note details a number of these techniques performed by the Scientific Anterior Cruciate Ligament Network International (SANTI) Study Group. Results: First, we describe a combined ACL reconstruction and double-bundle ALL reconstruction using hamstring autograft. Secondly, we describe a single-bundle ALL reconstruction using gracilis autograft. Thirdly, we describe an ALL reconstruction technique using a knotless soft anchor, which provides shallow fixation and prevents tunnel convergence. Finally, we describe a technique for ALL repair. Conclusion: Several techniques have been described to repair and reconstruct the ALL, all offering significant advantages over an isolated ACL reconstruction. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication
Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial
No full textBACKGROUND: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34). FINDINGS: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease. INTERPRETATION: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies. FUNDING: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking
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