Objective
The aim was to investigate the monitoring, interventions, and occurrence of critical, potentially life‐threatening incidents in patients with Dravet syndrome (DS) and caregivers’ knowledge ...about sudden unexpected death in epilepsy (SUDEP).
Methods
This multicenter, cross‐sectional study of patients with DS and their caregivers in Germany consisted of a questionnaire and prospective diary querying the disease characteristics and demographic data of patients and caregivers.
Results
Our analysis included 108 questionnaires and 82 diaries. Patients with DS were 49.1% male (n = 53), with a mean age of 13.5 (SD ± 10.0 years) and primary caregivers were 92.6% (n = 100) female, with a mean age of 44.7 (SD ± 10.6 years). Monitoring devices were used regularly by 75.9% (n = 82) of caregivers, and most monitored daily/nightly. Frequently used devices were pulse oximeters (64.6%), baby monitors (64.6%), thermometers (24.1%), and Epi‐Care (26.8%). Younger caregiver and patient age and history of status epilepticus were associated with increased use of monitoring, and 81% of monitor users reported having avoided a critical incident with nocturnal monitoring. The need for resuscitation due to cardiac or respiratory arrest was reported by 22 caregivers (20.4%), and most cases (72.7%) were associated with a seizure. Caregivers reported frequently performing interventions at night, including oropharyngeal suction, oxygenation, personal hygiene, and change of body position. Most caregivers were well informed about SUDEP (n = 102; 94%) and monitored for a lateral or supine body position; however, only 39.8% reported receiving resuscitation training, whereas 52.8% (n = 57) knew what to do in case the child's breathing or heart activity failed.
Significance
Critical incidents and the need for resuscitation are reported frequently by caregivers and may be related to high mortality and SUDEP rates in DS. Resuscitation training is welcomed by caregivers and should be continuously provided. Oxygen monitoring devices are frequently used and considered useful by caregivers.
Complex large models of multi-scale microstructures of porous media do not exist in a manner adequately efficient to render their comprehensive analysis of textural and structural properties ...possible. The simulation of experimental processes, such as gas adsorption, raises two issues. First, the modeling of these complex materials must be sufficiently realistic. This implies that the numerical twin of the porous material must consider three essential aspects: a spatial structure defining different scales of porosity, comparable textural and structural properties of the real material and irregular pore morphology. Secondly, efficient algorithms must be developed to mimic the quasi-static phase transition behavior of fluids in a realistic manner. The proposed simulation approach allows to handle the physico-chemical phenomena inside complex materials by means of well-established mathematical operators. Morphological operators are used to efficiently mimic processes such as surface adsorption and pore filling. Fluid percolation that provokes phase transition is simulated by labeled connected components. This method relies entirely on morphological and structural operators, which has the advantage of substantially reducing the calculation time compared to that of density functional theory and molecular simulations-based approaches. In contrast to oversimplified models characterized by ideal pore shape and unconnected pores, our approach enables us to calculate the adsorption isotherm of realistic random models where pore morphology and porous network topology are unknown beforehand. We demonstrate that our model succeed in reproducing the adsorption isotherm of two well-known model materials (SBA-15 and KIT-5) and mesoporous alumina, represented by Cox Boolean models.
Display omitted
•Morphological operators allow mimicking the processes of gas adsorption.•The presented method is not time consuming and handles realistic models of porous media.•The obtained adsorption isotherms of SBA-15, KIT-5 and mesoporous alumina are close to the experimental curves.
Abstract Background Factors influencing excessive weight gain in pregnancy have not been well-studied among urban, low-income women. Methods This prospective cohort study of 94 prenatal care patients ...at a large university hospital in Philadelphia examined associations of modifiable midpregnancy behaviors and nonmodifiable or early pregnancy factors with excessive gestational weight gain. Data were collected through questionnaires and medical record abstraction from 2009 to 2011. Findings The majority of women were African American (83%) and all (100%) received Medicaid. Nearly two thirds (60%) were overweight or obese in early pregnancy and 41% experienced excessive gain. In multivariable logistic regression analyses, significant predictors of excessive gestational weight gain included high early pregnancy body mass index (odds ratio OR, 4.20; 95% confidence interval CI, 1.43–12.34 for overweight/obese vs. normal weight), nulliparity (OR, 3.35; 95% CI, 1.17–9.62 for nulliparity vs. multiparity), and clinician advice discordant with Institute of Medicine guidelines (OR, 5.88; 95% CI, 1.04–33.32 for discordant vs. concordant advice). Watching under 2 hours of television daily (OR, 0.18; 95% CI, 0.03–1.03), and engaging in regular physical activity during pregnancy (OR, 0.35; 95% CI, 0.11–1.09) were suggestive of a reduced risk of excessive gain. Conclusions In this sample of urban, low-income women, high early pregnancy body mass index, nulliparity, and discordant clinician advice were directly associated with excessive gestational weight gain, with a trend toward decreased risk for viewing fewer hours of television and engaging in regular physical activity. Intervening on these targets may optimize gestational weight gain and promote long-term maternal health.
A comprehensive characterization of lung adenocarcinoma (LADC) clinical features is currently missing. We prospectively evaluated Caucasian patients with early‐stage LADC. Patients with LADC ...diagnosed between 2011 and 2015 were prospectively assessed for lung resection with curative intent. Fifty clinical, pathologic, radiologic, and molecular variables were recorded. Patients were followed till death/study conclusion. The main findings were compared to a separate cohort from France. Of 1943 patients evaluated, 366 were enrolled (18.8%; 181 female; 75 never‐smokers; 28% of registered Bavarian cases over the study period). Smoking and obstruction were significantly more prevalent in GLAD compared with adult Bavarians (P < 0.0001). Ever‐smoker tumors were preferentially localized to the upper lobes. We observed 120 relapses and 74 deaths over 704 cumulative follow‐up years. Median overall and disease‐free survival were >7.5 and 3.6 years, respectively. Patients aged <45 or >65 years, resected >60 days postdiagnosis, with abnormal FVC/DLCOVA, N2/N3 stage, or solid histology had significantly decreased survival estimates. These were fit into a weighted locoregional LADC death risk score that outperformed pTNM7 in predicting survival in the GLAD and in our second cohort. We define the clinical gestalt of locoregional LADC and provide a new clinical tool to predict survival, findings that may aid future management and research design.
We designed a study that longitudinally profiled the phenotype of 366 patients with resected lung adenocarcinoma and identified multiple novel aspects of the phenotype of contemporary locoregional lung adenocarcinoma, such as its sex indifference, its striking upper lobe predominance, and the early timing of pleural relapse and we developed a simple clinical tool to predict survival that outperforms the current staging system.
Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs ...and cost-driving factors associated with various organ manifestations in TSC patients.
A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany.
The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7-21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 95% confidence interval (95% CI) EUR 4088-5863, median EUR 2062 per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027-1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221-3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193-586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs.
This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.
DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
Zusammenfassung
Eine barrierefreie Teilnahme am alltäglichen Leben stellt für Menschen mit aktiver Epilepsie häufig eine Herausforderung dar. Epileptische Anfälle können in Kindergarten, Schule und ...am Arbeitsplatz sowie im häuslichen Umfeld Unsicherheit und Überforderung hervorrufen. Individuell erstellte Pläne für Betreuende, Angehörige, Aufsichtspersonen und den Rettungsdienst sollen im Falle eines akuten Anfalls geeignete Handlungsanweisungen geben. Bisher gibt es hierfür im deutschsprachigen Raum keine standardisierten Vorlagen. Mit den Handlungsplänen bei epileptischen Anfällen für Laien (HEAL) bzw. Therapeuten (HEAT) werden hier 2 Formulare vorgestellt, die zum einen eine standardisierte Grundlage bieten und andererseits leicht auf den individuellen Bedarf angepasst werden können.
The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID,
n
= 7) and non-ID (
n
= 8) ...mares. Horses were individually housed and fed timothy grass hay and two daily concentrate meals so that the total diet provided 120% of daily DE requirements for maintenance. All horses were given intramuscular bromocriptine injections (0.1 mg/kg BW) every 3 days for 14 days. Before and after 14 days of treatment horses underwent a combined glucose-insulin tolerance test (CGIT) to assess insulin sensitivity and a feed challenge (1 g starch/kg BW from whole oats) to evaluate postprandial glycemic and insulinemic responses. ID horses had higher basal plasma concentrations of insulin (
P
= 0.01) and triglycerides (
P
= 0.02), and lower concentrations of adiponectin (
P
= 0.05) compared with non-ID horses. The CGIT response curve showed that ID horses had slower glucose clearance rates (
P
= 0.02) resulting in a longer time in positive phase (
P
= 0.03) and had higher insulin concentrations at 75 min (
P
= 0.0002) compared with non-ID horses. Glucose (
P
= 0.02) and insulin (
P
= 0.04) responses to the feeding challenge were lower in non-ID compared to ID horses. Regardless of insulin status, bromocriptine administration increased hay intake (
P
= 0.03) and decreased grain (
P
< 0.0001) and total DE (
P
= 0.0002) intake. Bromocriptine treatment decreased plasma prolactin (
P
= 0.0002) and cholesterol (
P
= 0.10) and increased (
P
= 0.02) adiponectin concentrations in all horses. Moreover, in both groups of horses, bromocriptine decreased glucose clearance rates (
P
= 0.02), increased time in positive phase (
P
= 0.04) of the CGIT and increased insulin concentrations at 75 min (
P
= 0.001). The postprandial glycemic (
P
= 0.01) and insulinemic (
P
= 0.001) response following the oats meal was lower after bromocriptine treatment in all horses. In conclusion, in contrast to data in humans and rodents, bromocriptine treatment reduced insulin sensitivity in all horses, regardless of their insulin status. These results indicate that the physiological effects of EA might be different in horses compared to other species. Moreover, because bromocriptine shares a high degree of homology with natural EA, further investigation is warranted in horses grazing endophyte-infected grasses.
Background
The approval of everolimus (EVE) for the treatment of angiomyolipoma (2013), subependymal giant cell astrocytoma (2013) and drug-refractory epilepsy (2017) in patients with tuberous ...sclerosis complex (TSC) represents the first disease-modifying treatment option available for this rare and complex genetic disorder.
Objective
The objective of this study was to analyse the use, efficacy, tolerability and treatment retention of EVE in patients with TSC in Germany from the patient’s perspective.
Methods
A structured cross-age survey was conducted at 26 specialised TSC centres in Germany and by the German TSC patient advocacy group between February and July 2019, enrolling children, adolescents and adult patients with TSC.
Results
Of 365 participants, 36.7% (
n
= 134) reported the current or past intake of EVE, including 31.5% (
n
= 115) who were taking EVE at study entry. The mean EVE dosage was 6.1 ± 2.9 mg/m
2
(median: 5.6 mg/m
2
, range 2.0–15.1 mg/m
2
) in children and adolescents and 4 ± 2.1 mg/m
2
(median: 3.7 mg/m
2
, range 0.8–10.1 mg/m
2
) in adult patients. An early diagnosis of TSC, the presence of angiomyolipoma, drug-refractory epilepsy, neuropsychiatric manifestations, subependymal giant cell astrocytoma, cardiac rhabdomyoma and overall multi-organ involvement were associated with the use of EVE as a disease-modifying treatment. The reported efficacy was 64.0% for angiomyolipoma (75% in adult patients), 66.2% for drug-refractory epilepsy, and 54.4% for subependymal giant cell astrocytoma. The overall retention rate for EVE was 85.8%. The retention rates after 12 months of EVE therapy were higher among adults (93.7%) than among children and adolescents (88.7%; 90.5% vs 77.4% after 24 months; 87.3% vs 77.4% after 36 months). Tolerability was acceptable, with 70.9% of patients overall reporting adverse events, including stomatitis (47.0%), acne-like rash (7.7%), increased susceptibility to common infections and lymphoedema (each 6.0%), which were the most frequently reported symptoms. With a total score of 41.7 compared with 36.8 among patients not taking EVE, patients currently being treated with EVE showed an increased Liverpool Adverse Event Profile. Noticeable deviations in the sub-items ‘tiredness’, ‘skin problems’ and ‘mouth/gum problems’, which are likely related to EVE-typical adverse effects, were more frequently reported among patients taking EVE.
Conclusions
From the patients’ perspective, EVE is an effective and relatively well-tolerated disease-modifying treatment option for children, adolescents and adults with TSC, associated with a high long-term retention rate that can be individually considered for each patient. Everolimus therapy should ideally be supervised by a centre experienced in the use of mechanistic target of rapamycin inhibitors, and adverse effects should be monitored on a regular basis.
This study aimed to measure health-related quality of life (HRQOL) in children and adolescents with tuberous sclerosis complex (TSC) and quality of life (QOL) and depressive symptoms among ...caregivers.
Adequate metrics were used to assess HRQOL in children and adolescents with TSC (4–18 years, KINDLR) as well as QOL (EQ-5D) and symptoms of depression (BDI-II) among caregivers. Predictors for reduced HRQOL and depressive symptoms were identified by variance analysis, ordinal regression, and bivariate correlation.
The mean HRQOL score was 67.9 ± 12.7, and significantly lower values were associated with increasing age, attending special needs education, TSC-associated psychiatric symptoms, and drug-related adverse events. The mean QOL of caregivers was 85.4 ± 15.7, and caregiver's sex, TSC mutation locus, familial TSC clustering, special needs education, degree of disability, care dependency, presence of TSC-associated psychiatric symptoms, and TSC severity were significant predictors of lower QOL. Depressive symptoms were identified in 45.7% of caregivers, associated with female sex of the caregiver, familial TSC clustering, special needs education, and presence of TSC-associated psychiatric symptoms of the child. Multivariate regression analysis revealed adolescence and drug-related adverse events as significant predictors for lower HRQOL in TSC children, and TSC2 variants predicted lower QOL and depressive symptoms in caregivers.
Compared with other chronic diseases, such as headache, diabetes or obesity, children with TSC have significantly lower HRQOL, which further decreases during adolescence. A decreased HRQOL of patients correlates with a lower QOL and increased symptoms of depression of their caregivers. These results may improve the comprehensive therapy and care of children and adolescents with TSC and their families and caregivers.
DRKS, DRKS00016045. Registered 01 March 2019, http://www.drks.de/DRKS00016045.
•Multicenter study in 184 children with TSC as well as their caregivers•Children with TSC have significantly lower HRQOL than the normal population•Adolescence, drug-related adverse events and the severity of TSC manifestation impact HRQOL•Caregivers have lower QOL and more depressive symptoms than the normal population•TSC2 variants were predictive of lower QOL and increased depressive symptoms in caregivers
Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various ...disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).
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