Highlights • Resting state EEG and MEG recordings are increasingly used for functional connectivity and functional brain network analysis. • We highlight advantages and disadvantages of ...methodological choices throughout the recording and analysis pipeline and how this may affect construction of functional connectivity and networks. • We give several recommendations for subject instructions and data acquisition for resting state neurophysiological research.
Objective To determine the attributable mortality caused by delirium in critically ill patients.Design Prospective cohort study.Setting 32 mixed bed intensive care unit in the Netherlands, January ...2011 to July 2013.Participants 1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours.Exposures Trained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium.Main outcome measure Mortality during admission to an intensive care unit.Results Among 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P<0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval −7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval −0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76).Conclusions Overall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality.Trial registration Clinicaltrials.gov NCT01905033.
Intraplaque hemorrhage contributes to lipid core enlargement and plaque progression, leading to plaque destabilization and stroke. The mechanisms that contribute to the development of intraplaque ...hemorrhage are not completely understood. A higher incidence of intraplaque hemorrhage and thin/ruptured fibrous cap (upstream of the maximum stenosis in patients with severe ≥70% carotid stenosis) has been reported. We aimed to noninvasively study the distribution of intraplaque hemorrhage and a thin/ruptured fibrous cap in patients with mild-to-moderate carotid stenosis.
Eighty-eight symptomatic patients with stroke (<70% carotid stenosis included in the Plaque at Risk study) demonstrated intraplaque hemorrhage on MR imaging in the carotid artery plaque ipsilateral to the side of TIA/stroke. The intraplaque hemorrhage area percentage was calculated. A thin/ruptured fibrous cap was scored by comparing pre- and postcontrast black-blood TSE images. Differences in mean intraplaque hemorrhage percentages between the proximal and distal regions were compared using a paired-samples
test. The McNemar test was used to reveal differences in proportions of a thin/ruptured fibrous cap.
We found significantly larger areas of intraplaque hemorrhage in the proximal part of the plaque at 2, 4, and 6 mm from the maximal luminal narrowing, respectively: 14.4% versus 9.6% (
= .04), 14.7% versus 5.4% (
< .001), and 11.1% versus 2.2% (
= .001). Additionally, we found an increased proximal prevalence of a thin/ruptured fibrous cap on MR imaging at 2, 4, 6, and 8 mm from the MR imaging section with the maximal luminal narrowing, respectively: 33.7% versus 18.1%,
= .007; 36.1% versus 7.2%,
< .001; 33.7% versus 2.4%,
= .001; and 30.1% versus 3.6%,
= .022.
We demonstrated that intraplaque hemorrhage and a thin/ruptured fibrous cap are more prevalent on the proximal side of the plaque compared with the distal side in patients with mild-to-moderate carotid stenosis.
Epidemiological evidence regarding the relationship between fructose intake and intrahepatic lipid (IHL) content is inconclusive. We, therefore, assessed the relationship between different sources of ...fructose and IHL at the population level.
We used cross-sectional data from The Maastricht Study, a population-based cohort study (n = 3,981; mean ± SD age: 60 ± 9 years; 50% women). We assessed the relationship between fructose intake (assessed with a food-frequency questionnaire)-total and derived from fruit, fruit juice, and sugar-sweetened beverages (SSB)-and IHL (quantified with 3T Dixon MRI) with adjustment for age, sex, type 2 diabetes, education, smoking status, physical activity, and intakes of total energy, alcohol, saturated fat, protein, vitamin E, and dietary fiber.
Energy-adjusted total fructose intake and energy-adjusted fructose from fruit were not associated with IHL in the fully adjusted models (P = 0.647 and P = 0.767). In contrast, energy-adjusted intake of fructose from fruit juice and SSB was associated with higher IHL in the fully adjusted models (P = 0.019 and P = 0.009). Individuals in the highest tertile of energy-adjusted intake of fructose from fruit juice and SSB had a 1.04-fold (95% CI 0.99; 1.11) and 1.09-fold (95% CI 1.03; 1.16) higher IHL, respectively, in comparison with the lowest tertile in the fully adjusted models. Finally, the association for fructose from fruit juice was stronger in individuals with type 2 diabetes (P for interaction = 0.071).
Fructose from fruit juice and SSB is independently associated with higher IHL. These cross-sectional findings contribute to current knowledge in support of measures to reduce the intake of fructose-containing beverages as a means to prevent nonalcoholic fatty liver disease at the population level.
Due partly to physicians' unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus ...disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression.
We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3-6 months and analyzed using repeated-measures ANOVA.
Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were included in the study. Although skeletal muscle weakness was typically distributed in a limb-girdle pattern, many patients had unfamiliar features such as ptosis (23%), bulbar weakness (28%), and scapular winging (33%). During follow-up (average 1.6 years, range 0.5-4.2 years), skeletal muscle strength deteriorated significantly (mean declines of -1.3% point/year for manual muscle testing and of -2.6% points/year for hand-held dynamometry; both p<0.001). Longer disease duration (>15 years) and pulmonary involvement (forced vital capacity in sitting position <80%) at study entry predicted faster decline. On average, forced vital capacity in supine position deteriorated by 1.3% points per year (p=0.02). Decline in pulmonary function was consistent across subgroups. Ten percent of patients declined unexpectedly fast.
Recognizing patterns of common and less familiar characteristics in adults with Pompe disease facilitates timely diagnosis. Longer disease duration and reduced pulmonary function stand out as predictors of rapid disease progression, and aid in deciding whether to initiate enzyme replacement therapy, or when.
STUDY QUESTION
Is the long-term decline of ovarian function, as reflected by a decrease in serum anti-Müllerian hormone (AMH) concentration, accelerated over time in female childhood cancer survivors ...(CCS) as compared to healthy women of the same age?
SUMMARY ANSWER
The median decline of AMH levels in long-term female CCS is not accelerated and similar to that observed in healthy controls.
WHAT IS KNOWN ALREADY
Gonadal function is compromised in female CCS treated with chemotherapy and/or radiation therapy. Ovarian function is most compromised in survivors treated with total body irradiation, abdominal or pelvic irradiation, stem cell transplantation or high doses of alkylating agents.
STUDY DESIGN SIZE, DURATION
Longitudinal single-centre cohort study in 192 CCS in Rotterdam, The Netherlands, between 2001 and 2014.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Serum AMH levels of 192 adult female CCS were assessed, at least five years after cessation of treatment and at a follow-up visit with a median of 3.2 years (range: 2.1–6.0) later and were compared to the age-based P50 of AMH in healthy controls.
MAIN RESULTS AND THE ROLE OF CHANCE
Median AMH levels were below the P50 at both visit 1 (−0.59 µg/L) and at visit 2 (−0.22 µg/L). In women with a sustained ovarian function (AMH > 1.0 µg/L), the decline in AMH is similar to that in the normal population (difference in decline per year: −0.07 µg/L (range: −2.86 to 4.92), P = 0.75). None of the treatment modalities was correlated with a significant acceleration of decline of AMH per year.
LIMITATIONS REASONS FOR CAUTION
We selected CCS that visited our late effect outpatient clinic and who had two AMH levels available. It is conceivable that women without any apparent late effects of treatment as well as women with extreme late effects, which might be the ones with the largest impact on ovarian function, could be more likely to be lost to follow-up. However, general characteristics did not differ between the included and excluded patients.
WIDER IMPLICATIONS OF THE FINDINGS
While prospective longitudinal research is required to strengthen our findings, they may help physicians to counsel female CCS about their expected reproductive lifespan.
STUDY FUNDING/COMPETING INTEREST(S)
A.L.F.v.d.K., M.M.v.d.H.-E. and S.M.F.P. are supported by FP7-PanCare LIFE. J.S.E.L. has received grants from the following companies (in alphabetical order): Ferring, Merck Serono, Merck Sharp and Dome, Organon, Serono, Shering Plough and Shering. The other authors have no conflicts of interest to declare.
Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities ...during long-term follow-up is unknown. We describe the long-term follow-up of dilated cardiomyopathy (DCM) in DMD/BMD carriers.
A long-term follow-up study was performed among Dutch DMD/BMD carriers first analyzed in 1995. A cardiac history was taken, and all carriers were assigned a functional score to assess skeletal muscle involvement. Electrocardiography and M-mode and 2-D echocardiography were performed. DCM was defined as an enlarged left ventricle with a global left ventricle dysfunction or fractional shortening less than 28%. Slow vital capacity of the lung was measured by a hand-held spirometer.
Ninety-nine carriers were monitored with a median follow-up of 9 years (range 7.0-10.6 years). Eleven carriers with DCM (10 DMD, 1 BMD) were identified. Nine of them developed DCM in the follow-up period. One of the patients with DCM reported in the 1995 study died of cardiac failure at age 57 years. DCM was more frequently found in carriers who were functionally symptomatic.
Cardiac abnormalities in DMD/BMD carriers are progressive, as in patients with DMD/BMD.
The flower perianth has various, non‐mutually exclusive functions, such as visual signalling to pollinators and protecting the reproductive organs from the elements and from florivores, but how ...different perianth structures and their different sides play a role in these functions is unclear. Intriguingly, in many species there is a clear colour difference between the different sides of the perianth, with colour patterns or pigmentation present on only one side. Any adaptive benefit from such colour asymmetry is unclear, as is how the asymmetry evolved. In this viewpoint paper, we address the phenomenon of flowers with differently coloured inner and outer perianth sides, focusing on petals of erect flowers. Guided by existing literature and our own observations, we delineate three non‐mutually exclusive evolutionary hypotheses that may explain the factors underlying differently coloured perianth sides. The pollen‐protection hypothesis predicts that the outer side of petals contributes to protect pollen against UV radiation, especially during the bud stage. The herbivore‐avoidance hypothesis predicts that the outer side of petals reduces the flower's visibility to herbivores. The signalling‐to‐pollinators hypothesis predicts that flower colours evolve to increase conspicuousness to pollinators. The pollen‐protection hypothesis, the herbivore‐avoidance hypothesis, and the signalling‐to‐pollinators hypothesis generate largely but not entirely overlapping predictions about the colour of the inner and outer side of the petals. Field and laboratory research is necessary to disentangle the main drivers and adaptive significance of inner–outer petal side colour asymmetry.
Evolutionary hypotheses aimed at explaining why inner and outer sides of petals are often differently coloured.
Increasing evidence indicates that harmful effects are associated with the use of physical restraint.
To characterize the use of physical restraint in intensive care units. Prevalence, adherence to ...protocols, and correlates of the use of physical restraint were determined. For comparisons between ICUs, adjustments were made for differences in patients' characteristics.
A prospective, cross-sectional, observational multicenter study with a representative sample (n = 25) of all Dutch intensive care units, ranging from local hospitals to academic centers. Each unit was visited twice, and all 379 patients admitted during these visits were included and were examined for use of physical restraint.
Physical restraint was used in 23% of all patients (range, 0%-56% for different units). Of all 346 nurses interviewed, 31% reported using a protocol when applying physical restraint. When corrections were made for clustering within units, the risk for use of physical restraint was increased in patients with delirium or coma, in patients who could not communicate verbally, and in patients receiving psychoactive or sedative medications. Sex, severity of illness, and nurse to patient ratio were not independently related to use of physical restraint. In 11 units (44%), use of physical restraint was more frequent than expected on the basis of patients' characteristics, although this finding was not significant.
Physical restraint is frequently used in Dutch intensive care units. The differences in frequency between units suggest that opportunities exist to limit the use of physical restraint.
There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease.
The aim of this study was to investigate the effects of fructose restriction on ...intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator.
Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center.
Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P < 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups.
Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group. This trial was registered at clinicaltrials.gov as NCT03067428.
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