50 research outputs found
Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial
BACKGROUND: Helicobacter pylori gastritis may progress to glandular
atrophy and intestinal metaplasia, conditions that predispose to gastric
cancer. Profound suppression of gastric acid is associated with increased
severity of H pylori gastritis. This prospective randomised study aimed to
investigate whether H pylori eradication can influence gastritis and its
sequelae during long term omeprazole therapy for gastro-oesophageal reflux
disease (GORD). METHODS: A total of 231 H pylori positive GORD patients
who had been treated for > or =12 months with omeprazole maintenance
therapy (OM) were randomised to either continuation of OM (OM only; n =
120) or OM plus a one week course of omeprazole, amoxycillin, and
clarithromycin (OM triple; n = 111). Endoscopy with standardised biopsy
sampling as well as symptom evaluation were performed at baseline and
after one and two years. Gastritis was assessed according to the Sydney
classification system for activity, inflammation, atrophy, intestinal
metaplasia, and H pylori density. RESULTS: Corpus gastritis activity at
entry was moderate or severe in 50% and 55% of the OM only and OM triple
groups, respectively. In the OM triple group, H pylori was eradicated in
90 (88%) patients, and activity and inflammation decreased substantially
in both the antrum and corpus (p<0.001, baseline v two years). Atrophic
gastritis also improved in the corpus (p<0.001) but not in the antrum. In
the 83 OM only patients with continuing infection, there was no change in
antral and corpus gastritis activity or atrophy, but inflammation
increased (p<0.01). H pylori eradication did not alter the dose of
omeprazole required, or reflux symptoms. CONCLUSIONS: Most H pylori
positive GORD patients have a corpus predominant pangastritis during
omeprazole maintenance therapy. Eradication of H pylori eliminates gastric
mucosal inflammation and induces regression of corpus glandular atrophy. H
pylori eradication did not worsen reflux disease or lead to a need for
increased omeprazole maintenance dose. We therefore recommend eradication
of H pylori in GORD patients receiving long term acid suppression
Improved in vivo detection of cortical lesions in multiple sclerosis using double inversion recovery MR imaging at 3 Tesla
Objective: To investigate the impact of a higher magnetic field strength of 3 Tesla (T) on the detection rate of cortical lesions in multiple sclerosis (MS) patients, in particular using a dedicated double inversion recovery (DIR) pulse sequence. Methods: Thirty-four patients with clinically isolated syndromes or definite MS were included. All patients underwent magnetic resonance imaging (MRI) at 1.5 T and 3 T, including T2-weighted turbo spin echo (TSE), fluid-attenuated inversion recovery (FLAIR) and DIR sequences. All images were analysed for focal lesions categorised according to their anatomical location. Results: The total number of detected lesions was higher at 3 T across all pulse sequences. We observed significantly higher numbers of lesions involving the cortex at 3 T using a DIR sequence. DIR at 3 T showed 192% more pure intracortical (p<0.001) and 30% more mixed grey matter-white matter lesions (p=0.008). No significant increase in cortical lesions could be detected on the FLAIR and T2-weighted images. Using the T2-weighted and FLAIR sequences, significantly more lesions could be detected at 3 T in the infratentorial, periventricular and juxtacortical white matter. Conclusion: DIR brain MR imaging at 3 T substantially improves the sensitivity of the detection of cortical lesions compared with the standard magnetic field strength of 1.5 T. © European Society of Radiology 2009
Multifocal motor neuropathy is not associated with altered innate immune responses to endotoxin
Objective: Antibody- and complement-mediated peripheral nerve inflammation are central in the pathogenesis of MMN. Here, we studied innate immune responses to endotoxin in patients with MMN and controls to further our understanding of MMN risk factors and disease modifiers. Methods: We stimulated whole blood of 52 patients with MMN and 24 controls with endotoxin and collected plasma. With a multiplex assay, we determined levels of the immunoregulating proteins IL-1RA, IL-1ÎČ, IL-6, IL-10, IL-21, TNF-α, IL-8 and CD40L in unstimulated and LPS-stimulated plasma. We compared baseline and stimulated protein levels between patients and controls and correlated concentrations to clinical parameters. Results: Protein level changes after stimulation were comparable between groups (p > 0.05). IL-1RA, IL-1ÎČ, IL-6 and IL-21 baseline concentrations showed a positive correlation with monthly IVIg dosage (all corrected p-values < 0.016). Patients with anti-GM1 IgM antibodies showed a more pronounced IL-21 increase after stimulation (p 0.048). Conclusions: Altered endotoxin-induced innate immune responses are unlikely to be a susceptibility factor for MMN
Effectiveness of Omicron XBB.1.5 vaccine against infection with SARS-CoV-2 Omicron XBB and JN.1 variants, prospective cohort study, the Netherlands, October 2023 to January 2024
We estimated vaccine effectiveness (VE) of SARS-CoV-2 Omicron XBB.1.5 vaccination against self-reported infection between 9 October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible adults who had previously received at least one booster. VE was 41% (95%âŻCI: 23-55) in 18-59-year-olds and 50% (95%âŻCI: 44-56) in 60-85-year-olds. Sequencing data suggest lower protection against the BA.2.86 (including JN.1) variant from recent prior infection (ORâŻ=âŻ2.8; 95%âŻCI:1.2-6.5) and, not statistically significant, from XBB.1.5 vaccination (ORâŻ=âŻ1.5; 95%âŻCI:0.8-2.6)
Physiological-based cord clamping in very preterm infants:the Aeration, Breathing, Clamping 3 (ABC3) trialâstatistical analysis plan for a multicenter randomized controlled trial
Background: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. Methods: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30Â weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2Â years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. Discussion: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. Trial registration: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.</p
Study protocol: optimization of complex palliative care at home via telemedicine. A cluster randomized controlled trial
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97378.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Due to the growing number of elderly with advanced chronic conditions, healthcare services will come under increasing pressure. Teleconsultation is an innovative approach to deliver quality of care for palliative patients at home. Quantitative studies assessing the effect of teleconsultation on clinical outcomes are scarce. The aim of this present study is to investigate the effectiveness of teleconsultation in complex palliative homecare. METHODS/DESIGN: During a 2-year recruitment period, GPs are invited to participate in this cluster randomized controlled trial. When a GP refers an eligible patient for the study, the GP is randomized to the intervention group or the control group. Patients in the intervention group have a weekly teleconsultation with a nurse practitioner and/or a physician of the palliative consultation team. The nurse practitioner, in cooperation with the palliative care specialist of the palliative consultation team, advises the GP on treatment policy of the patient. The primary outcome of patient symptom burden is assessed at baseline and weekly using the Edmonton Symptom Assessment Scale (ESAS) and at baseline and every four weeks using the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes are self-perceived burden from informal care (EDIZ), patient experienced continuity of medical care (NCQ), patient and caregiver satisfaction with the teleconsultation (PSQ), the experienced problems and needs in palliative care (PNPC-sv) and the number of hospital admissions. DISCUSSION: This is one of the first randomized controlled trials in palliative telecare. Our data will verify whether telemedicine positively affects palliative homecare. TRIAL REGISTRATION: The Netherlands National Trial Register NTR2817
Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trialâstatistical analysis plan for a multicenter randomized controlled trial
Background: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. Methods: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30Â weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2Â years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. Discussion: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. Trial registration: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019
Cerebral small vessel disease genomics and its implications across the lifespan
White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (pâ=â2.5Ă10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe
Association of common genetic variants with brain microbleeds
OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed geno