Congenital cytomegalovirus (CMV) infection can lead to severe neurological sequelae and (progressive) sensorineural deafness. Neonatal imaging data is mainly based on cranial ultrasound (US) and ...computed tomography (CT). The additional value of magnetic resonance imaging (MRI) was assessed in congenital CMV infection. The eleven infants studied had a gestational age between 34 and 41 weeks and a birth weight between 1000 and 2780 grams. All but 2 of the infants presented with microcephaly and jaundice at birth. The diagnosis was confirmed postnatally in all infants by isolation of the virus or a polymerase chain reaction (PCR) from the urine. Cranial US was performed in all, MRI in 6 during the neonatal period and later in infancy in 2. Auditory brainstem evoked responses (ABR) were performed in all survivors. US showed periventricular calcifications and/or lenticulostriate vasculopathy associated with mild to moderate ventricular dilatation in 10 of the 11 children. Periventricular (pseudo) cysts were seen in 6 children, being occipital in 4, temporal in 3 and fronto-parietal in 1. The cerebellum appeared to be small in 4 children. MRI provided additional information in 6 of the 8 children. Polymicrogyria in the perisylvian region was seen in 4 children, hippocampal dysplasia in 3 and cerebellar hypoplasia in 4 children. Abnormal signal intensity in the white matter was seen in 4 infants. ABRs were abnormal in 7 of the 9 children. Four children died in the neonatal period, 4 developed severe neurological sequelae, associated with epilepsy and sensorineural deafness in 3. Three children were still too young to be tested, but 2 of these showed sensorineural deafness. MRI provided important additional information, especially with regard to associated polymicrogyria, hippocampal dysplasia, and cerebellar hypoplasia. Calcifications were better seen using US. A combination of US and neonatal MRI should be recommended instead of a CT which is still recommended in the literature.
In the neonatal period, seizures rank among the most common neurological symptoms, often indicating an underlying serious neurological condition. It is remarkable that although new tools have been ...incorporated into the diagnosis of neonatal seizures, there is no consensus about the therapeutic approach among different doctors and institutions. Hence, although phenobarbital is still considered the initial drug of choice, the protocols reported in the literature show a great variability in the approach to treatment of refractory seizures. We used a questionnaire to gain information regarding the treatment of seizures in the neonatal period in different European institutions.
Conclusion: We conclude that phenobarbital is still the initial drug of choice followed by benzodiazepines, except in preterm infants with a birth weight below 1800 g. In refractory seizures, the use of continuous lidocaine infusion is most common. Of note, clinical studies with newer drugs have been mostly performed in the United States but not in Europe.
Anemia is more often seen in older patients. As the mean age of hip fracture patients is rising, anemia is common in this population. Allogeneic blood transfusion (ABT) and anemia have been pointed ...out as possible risk factors for poorer outcome in hip fracture patients.
In the timeframe 2005-2010, 1262 admissions for surgical treatment of a hip fracture in patients aged 65 years and older were recorded. Registration was prospective from 2008 on. Anemic and non-anemic patients (based on hemoglobin level at admission) were compared regarding clinical characteristics, mortality, delirium incidence, LOS, discharge to a nursing home and the 90-day readmission rate. Receiving an ABT, age, gender, ASA classification, type of fracture and anesthesia were used as possible confounders in multivariable regression analysis.
The prevalence of anemia and the rate of ABT both were 42.5%. Anemic patients were more likely to be older and men and had more often a trochanteric fracture, a higher ASA score and received more often an ABT. In univariate analysis, the 3- and 12-month mortality rate, delirium incidence and discharge to a nursing home rate were significantly worse in preoperatively anemic patients.In multivariable regression analysis, anemia at admission was a significant risk factor for discharge to a nursing home and readmission < 90 days, but not for mortality. Indication for ABT, age and ASA classification were independent risk factors for mortality at all moments, only the mortality rate for the 3-12 month interval was not influenced by ABT. An indication for an ABT was the largest negative contributor to a longer LOS (OR 2.26, 95% CI 1.73-2.94) and the second largest for delirium (OR 1.67, 95% CI 1.28-2.20).
This study has demonstrated that anemia at admission and postoperative anemia needing an ABT (PANT) were independent risk factors for worse outcome in hip fracture patients. In multivariable regression analysis, anemia as such had no effect on mortality, due to a rescue effect of PANT. In-hospital, 3- and 12-month mortality was negatively affected by PANT, with the main effect in the first 3 months postoperatively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Preclinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide ...as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov , number NCT01434225. Findings Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephalopathy. 14 of these infants (10 boys) were included in the study (dose allocation: 0·05 mg/kg, n=4; 0·1 mg/kg, n=3; 0·2 mg/kg, n=6; 0·3 mg/kg, n=1). All babies received at least one dose of bumetanide with the second dose of phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one because of dehydration. All but one infant also received aminoglycosides. Five infants met EEG criteria for seizure reduction (one on 0·05 mg/kg, one on 0·1 mg/kg and three on 0·2 mg/kg), and only two did not need rescue antiepileptic drugs (ie, met rescue criteria; one on 0·05 mg/kg and one on 0·3 mg/kg). We recorded no short-term dose-limiting toxic effects, but three of 11 surviving infants had hearing impairment confirmed on auditory testing between 17 and 108 days of age. The most common non-serious adverse reactions were moderate dehydration in one, mild hypotension in seven, and mild to moderate electrolyte disturbances in 12 infants. The trial was stopped early because of serious adverse reactions and limited evidence for seizure reduction. Interpretation Our findings suggest that bumetanide as an add-on to phenobarbital does not improve seizure control in newborn infants who have hypoxic ischaemic encephalopathy and might increase the risk of hearing loss, highlighting the risks associated with the off-label use of drugs in newborn infants before safety assessment in controlled trials. Funding European Community's Seventh Framework Programme.
Microencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia ...mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose‐ and time‐dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox‐modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.
The present study is the first to explore the potential of fucoidan, marine sulfated polysaccharide, for pancreatic islet encapsulation. Fucoidan has high fucose contents with sulfate groups, demonstrating potent antioxidant properties significantly alleviating oxidative stress and enhancing the viability and function of encapsulated beta cells. The fucoidan‐based hydrogel is thus assessed as a biomaterial for bioengineered immunoprotective beta cell replacement systems.
The aim of this study was to assess the additional value of diffusion-weighted magnetic resonance imaging (DW-MRI) compared to conventional magnetic resonance imaging (MRI) in new-born infants with ...arterial ischaemic stroke, with regard to the prediction of neurodevelopmental outcome.
Neonatal DW-MRI data were available in 15 infants with a gestational age of > or = 35 weeks and repeat MRI data were obtained in 12 of the 14 survivors. T(1)- and T(2)-weighted transverse images were obtained as well as 4-mm DWI slices. ADC maps were calculated in manually selected regions on the basis of the DWI scans. All 14 survivors were seen in the follow-up clinic and 12 were > 18 months when last seen.
T (2) hyperintensity was detected in the descending white matter tracts at the level of the internal capsule in 7 infants and in only one of these also at the level of the cerebral peduncles. Increased signal intensity (SI) was seen on DW-MRI in 8 infants in the descending white matter tract ipsilateral to the territorial infarct at the level of the internal capsule and in 5 of these also at the level of the cerebral peduncles. ADC maps were available in 12 infants. ADC values were calculated at the level of the cerebral peduncles, using the contralateral side as a reference value. A significantly reduced value was found in 3 of the 5 infants who showed an increased SI on DW-MRI. ADC maps were not available in the other two. Five of the seven infants with abnormalities on DW-MRI/ADC of the corticospinal tracts developed a mild to moderate hemiplegia, one showed an asymmetry of tone and one with only involvement of the anterior part of the internal capsule was normal at follow-up. Wallerian degeneration, seen at the level of the cerebral peduncles and/or the PLIC on the repeat MRI, was seen in the 5 infants who had shown acute changes of the corticospinal tracts in the neonatal period and who went on to develop motor sequelae.
Compared to MRI, DW-MRI and ADC maps provided additional, quantitative data of acute corticospinal tract injury at an early time point after the insult, especially at the level of the cerebral peduncles. The presence of increased SI on DW-MRI at the level of the PLIC and the cerebral peduncles in new-born infants with arterial ischaemic stroke is followed by Wallerian degeneration and subsequent development of hemiplegia.
The incidence of keratinocyte carcinomas is high and rapidly growing. Approximately 80% of keratinocyte carcinomas consist of basal cell carcinomas (BCC) with 50% of these being considered as ...low-risk tumors. Nevertheless, 83% of the low-risk BCC patients were found to receive more follow-up care than recommended according to the Dutch BCC guideline, which is one visit post-treatment for this group. More efficient management could reduce unnecessary follow-up care and related costs.
To study the efficacy, cost-utility, and budget impact of a personalized discharge letter for low-risk BCC patients compared with usual care (no personalized letter).
In a multi-center intervention study, a personalized discharge letter in addition to usual care was compared to usual care in first-time BCC patients. Model-based cost-utility and budget impact analyses were conducted, using individual patient data gathered via surveys. The outcome measures were number of follow-up visits, costs and quality adjusted life years (QALY) per patient.
A total of 473 first-time BCC patients were recruited. The personalized discharge letter decreased the number of follow-up visits by 14.8% in the first year. The incremental costs after five years were -€24.45 per patient. The QALYs were 4.12 after five years and very similar in both groups. The national budget impact was -€2,7 million after five years.
The distribution of a personalized discharge letter decreases the number of unnecessary follow-up visits and implementing the intervention in a large eligible population would results in substantial cost savings, contributing to restraining the growing BCC costs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • Saliva PCR is inferior to urine PCR in detecting a postnatal CMV infection in preterm infants. • About 10% of postnatal CMV infections are missed when screening saliva compared to urine, ...for CMV DNA. • Among symptomatic infants with postnatal CMV infection, saliva has equal sensitivity as urine.