A comparison of Simplified Acute Physiology Score II and Sepsis-related Organ Failure Assessment Score for prediction of mortality after Intensive Care Unit cardiac arrest.

BACKGROUND: This study investigates the predictive value and suitable cutoff values of the Sepsis-related Organ Failure Assessment Score (SOFA) and Simplified Acute Physiology Score II (SAPS-II) to predict mortality during or after Intensive Care Unit Cardiac Arrest (ICU-CA). METHODS: In this secondary analysis the ICU database of a German university hospital with five ICU was screened for all ICU-CA between 2016-2019. SOFA and SAPS-II were used for prediction of mortality during ICU-CA, hospital-stay and one-year-mortality. Receiver operating characteristic curves (ROC), area under the ROC (AUROC) and its confidence intervals were calculated. If the AUROC was significant and considered "acceptable," cutoff values were determined for SOFA and SAPS-II by Youden Index. Odds ratios and sensitivity, specificity, positive and negative predictive values were calculated for the cutoff values. RESULTS: A total of 114 (78 male; mean age: 72.8±12.5 years) ICU-CA were observed out of 14,264 ICU-admissions (incidence: 0.8%; 95% CI: 0.7-1.0%). 29.8% (N.=34; 95% CI: 21.6-39.1%) died during ICU-CA. SOFA and SAPS-II were not predictive for mortality during ICU-CA (P>0.05). Hospital-mortality was 78.1% (N.=89; 95% CI: 69.3-85.3%). SAPS-II (recorded within 24 hours before and after ICU-CA) indicated a better discrimination between survival and death during hospital stay than SOFA (AUROC: 0.81 [95% CI: 0.70-0.92] vs. 0.70 [95% CI: 0.58-0.83]). A SAPS-II-cutoff-value of 43.5 seems to be suitable for prognosis of hospital mortality after ICU-CA (specificity: 87.5%, sensitivity: 65.6%; SAPS-II>43.5: 87.5% died in hospital; SAPS-II<43.5: 65.6% survived; odds ratio:13.4 [95% CI: 3.25-54.9]). Also for 1-year-mortality (89.5%; 95% CI: 82.3-94.4) SAPS-II showed a better discrimination between survival and death than SOFA: AUROC: 0.78 (95% CI: 0.65-0.91) vs. 0.69 (95% CI: 0.52-0.87) with a cutoff value of the SAPS-II of 40.5 (specificity: 91.7%, sensitivity: 64.3%; SAPS-II>40.5: 96.4% died; SAPS-II<40.5: 42.3% survived; odd ratio: 19.8 [95% CI: 2.3-168.7]). CONCLUSIONS: Compared to SOFA, SAPS-II seems to be more suitable for prediction of hospital and 1-year-mortality after ICU-CA.

Rehabilitation in patients with newly diagnosed epilepsy: A controlled, 1-year follow-up study on a specialized inpatient rehabilitation program.

OBJECTIVES: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with newly diagnosed epilepsy (NDE), who had been referred within 1 year after diagnosis. METHODS: We performed an open, prospective, controlled study comparing a 1-year follow-up assessment of patients with NDE after completing a rehabilitation program at an epilepsy center (rehabilitation group) with a control group of patients with similar epilepsy duration, but without rehabilitation in the first year after diagnosis. Primary outcome measures comprised emotional adaptation to epilepsy, depression and anxiety; and secondary outcome measures were overall quality of life (QoL), overall health, perceived restrictions because of epilepsy, level of information about epilepsy, and employment status. RESULTS: Comparison of the admission data of 74 rehabilitation group patients (mean age and SD 47.7 ± 13.0 years) with the pre-rehabilitation assessment of 56 control patients (45.5 ± 12.1 years) revealed no significant differences concerning sociodemographic and health data. Comparison of the follow-up assessment of the rehabilitation group and the pre-rehabilitation assessment of the control group showed significantly better values for the rehabilitation group on emotional adaptation to epilepsy (p = .003), overall QoL (p = .006) and overall health (p = .011), perceived restrictions because of epilepsy, and subjective level of information about epilepsy (both p's < .001). There were no statistically significant differences concerning depression and anxiety or employment status (all p's > .50). One year after rehabilitation, patients in the rehabilitation group were more often seizure-free and less often on sickness absence than control group patients (both p's < .001). SIGNIFICANCE: Since reduced QoL shortly after diagnosis of NDE is associated with seizure recurrence, an early identification of patients with a greater need for support seems important. This epilepsy-related rehabilitation program showed lasting effects on several aspects of adaptation to epilepsy and QoL.

Efficacy of in-bed chest compressions depending on provider position during in-hospital cardiac arrest: a controlled manikin study.

BACKGROUND: In contrast to the pre-hospital environment, patients with in-hospital cardiac arrest are usually lying in a hospital bed. Interestingly, there are no current recommendations for optimal provider positioning. The present study evaluates in bed chest compression quality in different provider positions during in-hospital-cardiac-arrest. METHODS: Paramedics conducted four resuscitation scenarios: manikin lying on the floor with provider position kneeling next to the manikin (control group), manikin lying in a hospital bed with the provider kneeling astride, kneeling beside or standing next to the manikin. A resuscitation board was not used according to the current guideline recommendations. Quality of resuscitation, compression depth, compression rate and percentage of compressions with complete chest rebound were recorded. Afterwards, the paramedics were asked about subjective efficiency and fatigue. Data were analyzed using Generalized-Linear-Mixed-Models and, in addition, by non-parametric Friedman test. RESULTS: A total of 60 participants were recruited. The total quality of chest compressions was significantly higher in floor-based control position compared to the standing (P<.001) and both kneeling positions (P<.05). Also, the compression depth was significantly more guideline compliant in the control (P<.001) and the kneeling position (P<.05) compared to the standing position. The compression frequency as well as the complete chest wall recoil did not differ significantly. The standing position was rated as more fatiguing than the other positions (p≤0.001), kneeling beside as subjectively more efficient than the standing position (P<0.001). CONCLUSIONS: In case of an in-bed resuscitation, high quality chest compressions are possible. Kneeling astride or beside the patient should be preferred because these positions demonstrated a good chest compression quality and were more efficient and less exhausting.

Caries-preventing effect of a hydroxyapatite-toothpaste in adults: a 18-month double-blinded randomized clinical trial.

Background: Dental caries is a worldwide challenge for public health. The aim of this 18-month double-blinded, randomized, clinical trial was to compare the caries-preventing effect of a fluoride-free, hydroxyapatite toothpaste (test) and a toothpaste with sodium fluoride (1450 ppm fluoride; positive control) in adults. Methods: The primary endpoint was the percentage of subjects showing no increase in overall Decayed Missing Filled Surfaces (DMFS) index. The study was designed as non-inferiority trial. Non-inferiority was claimed if the upper limit of the exact one-sided 95% confidence interval for the difference of the primary endpoint DMFS between test and control toothpaste was less than the predefined margin of non-inferiority (Δ ≤ 20%). Results: In total, 189 adults were included in the intention-to-treat (ITT) analysis; 171 subjects finished the study per protocol (PP). According to the PP analysis, no increase in DMFS index was observed in 89.3% of subjects of the hydroxyapatite group and 87.4% of the subjects of the fluoride group. The hydroxyapatite toothpaste was not statistically inferior to a fluoride toothpaste with regard to the primary endpoint. Conclusion: Hydroxyapatite was proven to be a safe and efficient anticaries agent in oral care. Clinical trial registration: NCT04756557.

Efficacy of a specialized inpatient rehabilitation program in patients with early versus chronic epilepsy.

OBJECTIVE: To evaluate the efficacy of a specialized inpatient rehabilitation program in patients with early in comparison with chronic epilepsy. METHODS: We performed a prospective, open pre/post study using a parallel group design. Patients with early epilepsy (EE, treatment with anti-seizure medication [ASM] ≤ 1 year) or with chronic epilepsy (CE, ASM treatment > 5 years) completed questionnaires at the time of their admission to the rehabilitation program and at discharge. Outcome measures comprised scales from the PESOS questionnaire (PErformance, SOciodemographic aspects, Subjective estimation; e.g., emotional adaptation to epilepsy) as well as screening instruments for depression (Neurological Disorders Depression Inventory for Epilepsy, NDDI-E) and anxiety (Generalized Anxiety Disorder Scale, GAD-7). Linear mixed models (LMMs) were used to determine the effects of the program in the total group and to compare the effects between patients with EE and CE. RESULTS: The analyses included 79 patients with EE and 157 patients with CE. Baseline comparisons revealed differences in disease-related and sociodemographic variables (e.g., patients with EE were older, those with CE had a higher seizure frequency and a higher rate of unemployment; all p < .01). LMMs showed significant improvements in emotional adaptation to epilepsy, depression, anxiety, overall quality of life and overall health as well as in perceived overall restrictions because of epilepsy and the subjective level of information about epilepsy (all p < .001). Despite the different duration of epilepsy, baseline levels as well as improvements did not differ between patients with EE and CE (all p > .05) except for the perceived level of information, which was significantly lower in patients with EE at admission and improved to a higher extent in this group (both p < .001). CONCLUSION: Both patients with EE and patients with CE who are referred to a specialized comprehensive rehabilitation program benefit from the participation in this program with respect to emotional adaptation to epilepsy, aspects of quality of life, and level of information about epilepsy.

Validation of Conversion Factors for Therapeutic Drug Monitoring of Lacosamide, Lamotrigine, and Levetiracetam in Dried Capillary Blood.

BACKGROUND: Estimation of serum concentrations of antiseizure medications (ASMs) based on dried capillary blood is an alternative method for therapeutic drug monitoring of epilepsy. The aim of this study was to validate the conversion factors for lacosamide (LCM), lamotrigine (LTG), and levetiracetam (LEV), which were determined in an independent patient sample in a previous study, and identify the most accurate conversion method (simple ratio and regression). METHODS: Venous and capillary blood samples were collected from adult inpatients with epilepsy treated with LCM (n = 25), LTG (n = 27), and/or LEV (n = 29) before the morning dose (T1) and approximately 2 hours after (T2). Capillary blood was collected using volumetric absorptive microsampling, and the ASM concentrations were measured using a validated liquid chromatography-mass spectrometry method for dried blood samples. Serum concentrations were estimated using conversion factors and compared with those measured using routine laboratory methods. RESULTS: For all 3 ASMs, the simple ratio approach performed better than the regression approach. Intraclass correlation coefficients revealed a high agreement between the estimated and measured serum concentrations (LCM T1: 0.93, T2: 0.90; LTG T1: 0.91, T2: 0.91; and LEV T1: 0.97, T2: 0.94). The criteria of the European Medicines Agency for cross-validation were fulfilled for LCM (T1: 72%; T2: 75%) and LEV (T1: 86%; T2: 75%), whereas for LTG, this was only true for capillary blood concentrations ≤11 µ g/mL [42.9 µ mol/L; T1: 72% (vs. 63% for total range), T2: 67% (vs. 62%)]. CONCLUSIONS: Estimating serum concentrations using capillary blood concentrations is feasible and accurate for LCM and LEV over a wide concentration range, as found in clinical practice. The applicability of this mehod for LTG is limited by its greater variability at higher concentrations; however, acceptable results were achieved for the large proportion of patients with low and medium LTG concentrations.

Have attitudes toward epilepsy improved in Germany over the last 50 years?

OBJECTIVE: In Germany, six previous representative surveys on attitudes toward epilepsy (AE) have been conducted between 1967 and 2008 using the four original Caveness questions (CQs) from 1949 to 1980. The aims of this study were (1) to investigate changes in AE over the time span of 50 years, including the current survey in 2018 (2) to investigate the first-time emotional reactions measured with the Scales of Attitudes toward People with Epilepsy (SAPE) (3) to identify predictors of AE. METHODS: A representative face-to-face survey with CQ, in addition with the SAPE scales of Social Distance, Stereotypes, Personal Concerns, and Emotional Reactions was carried out in Germany in 2018. One thousand and twenty-six persons who ever had heard of epilepsy participated. Respondents who answered "don't know" in the CQs were subsequently asked to answer only yes/no. The analysis of trends from 1967 to 2018 was based on the pooled data of the surveys. The four CQs in the 2018 survey were included in the SAPE item pool and an exploratory principal axis factor analysis was performed. General linear models were performed to identify predictors. RESULTS: For all four CQs, the trend of improved AE was significant over the past 50 years. In the 2018 survey, excluding the "don't know" answer option increased the proportion of negative responses for contact of one's own children with a person with epilepsy (PWE) from 6.9% to 11.4% and for the marriage of one's own children with a PWE from 13.9% to 23.8%. When encountering a PWE, 30.1% would feel insecure or uncomfortable and nearly 60% were concerned that the PWE might be injured in case of a seizure. Knowing what to do in case of a seizure, knowing that seizures can be treated successfully, personal contact with a PWE along with younger age, and higher education were found to be the strongest predictors for positive AE identified by multivariate analyses. Exploratory principal axis factor analysis revealed that three of the four CQs items loaded > 0.30 at the factors of Social Distance and Stereotypes of SAPE but none on the factors measuring emotional reactions. SIGNIFICANCE: AE measured by CQs have markedly improved in Germany over the last 50 years. Germany is to our knowledge the only country with such a long-term trend investigation in AE. Negative AE may be underestimated by survey questions with "don't know" answer option. Emotional aspects of attitudes are underexposed resp. neglected in the CQs, which are used worldwide for measuring AE. Additional tools like SAPE can close this gap. The identified predictors may help to derive interventions against negative AE.

Persistent knowledge gaps between 2005 and 2020 in women with epilepsy: Comparison of multicenter studies from Germany.

OBJECTIVE: Epilepsy is a chronic condition that can affect patients of all ages. Women with epilepsy (WWE) require access to specific counseling and information regarding issues related to contraception, pregnancy, and hormonal effects on seizure control and bone mineral density. This study investigated the knowledge among WWE regarding their condition, and whether epilepsy-specific knowledge has improved over the last 15 years. METHODS: A total of 280 WWE aged 18 to 82 years participated in this multicenter, questionnaire-based study. The study was conducted at four epilepsy centers in Germany, between October 2020 and December 2020. Sociodemographic and epilepsy-specific data for participating women were analyzed and compared with the results of a similar survey performed in 2003-2005 among 365 WWE in Germany. RESULTS: The questionnaire-based survey revealed considerable knowledge deficits without significant improvements over the last 15 years, particularly among those with less education and with regards to information on the more pronounced effects of epilepsy in older WWE (>50 years), including interactions with menopause and osteoporosis. In WWE ≤29 years, a significant increase in the knowledge score was observed in 2020 compared with this age group in 2005 (mean 7.42 vs. 6.5, p = .036). Mothers frequently reported epilepsy-related concerns regarding childrearing, particularly of seizures scaring their child and the need to rely on other people. CONCLUSION: WWE continue to demonstrate inadequate epilepsy-related knowledge. Despite increasing information availability and the aspiration toward better awareness among medical professionals, overall knowledge has not increased sufficiently compared with the levels observed in recent studies.

Vaginal hormone-free moisturising cream is not inferior to an estriol cream for treating symptoms of vulvovaginal atrophy: Prospective, randomised study.

This prospective, open-label, multicentre, multinational, randomised trial investigated the non-inferiority of treatment with a vaginal hormone-free moisturising cream compared to a vaginal estriol (0.1%) cream in a panel of post-menopausal women suffering from symptoms of vulvovaginal dryness in a parallel group design. In total, 172 post-menopausal women were randomly allocated to either one of the two treatments, each administered for 43 days. The primary endpoint was the total severity score of subjective symptoms (dryness, itching, burning and pain unrelated to sexual intercourse) of the respective treatment period. Secondary endpoints were severity of single subjective symptoms (including dyspareunia if sexually active), impairment of daily life, Vaginal Health Index, as well as assessment of safety. In both groups, women treated with hormone-free moisturising cream and those treated with estriol cream, total severity score improved significantly compared to baseline by 5.0 (from 6.1 to 1.1) and by 5.4 (from 6.0 to 0.6), respectively, after 43 days of treatment (p < 0.0001). One-sided test of baseline differences (for a clinically relevant difference Δ = 1.5) confirmed the hormone-free moisturising cream to be non-inferior to the estriol cream. Severity of dyspareunia as well as impairment of daily life due to subjective symptoms, significantly improved for both treatment groups (p<0.0001). Subgroup analysis of women with mild or moderate impairment of daily life at baseline caused by "vaginal dryness" symptoms benefited from both creams, while women with severe impairment showed a significantly greater benefit from the estriol cream (p = 0.0032). Both treatments were well tolerated with no serious adverse events occurring. This study provides clinical evidence that a hormone-free vaginal moisturising cream cannot only improve vaginal dryness compared to an 0.1% estriol cream but also can relieve dyspareunia as well as improve woman's impairment of daily life, justifying its use as a first choice for mild or moderate vulvovaginal dryness symptoms.

The efficacy of Narrative Exposure Therapy for Children (KIDNET) as a treatment for traumatized young refugees versus treatment as usual: update to the study protocol for the multi-center randomized controlled trial YOURTREAT.

BACKGROUND: The trial YOURTREAT aims to compare the pragmatic, short-term psychotherapy Narrative Exposure Therapy for Children (KIDNET) with treatment as usual (TAU) for the treatment of young refugees in Germany. This update outlines changes made to the study protocol in response to the current COVID-19 pandemic with the aim of allowing the continuation of the clinical trial while ensuring the safety of the staff and the participants, maintaining methodological quality, and ensuring compliance with legal regulations. METHODS: The major amendments to the original study protocol include (1) the possibility of using telehealth technology for the conduction of diagnostic and therapy sessions, (2) a reduction of the diagnostic set, and (3) an increased flexibility in the time frame of the study protocol. DISCUSSION: The adaptations to the study protocol made it feasible to continue with the trial YOURTREAT during the COVID-19 pandemic. Although the diagnostic set had to be shortened, the primary outcomes and the main secondary outcomes remain unimpaired by the amendment. Therefore, we expect the trial to provide evidence regarding effective treatment options for young refugees in Germany, a population that has received little scientific attention so far and has only very limited access to mental health care in the German health care system. In light of the current pandemic, which globally increases the risk of mental problems, the situation for young refugees is likely to aggravate further. Thus, the clinical and social relevance of the present trial YOURTREAT is even more important in these particular times. TRIAL REGISTRATION: German Clinical Trials Register (Deutsches Register Klinischer Studien; DRKS) DRKS00017222 . Registered on May 15, 2019.

Attitudes toward epilepsy assessed by the SAPE questionnaire in Germany - Comparison of its psychometric properties and results in a web-based vs. face-to-face survey.

OBJECTIVE: The aims of this study were (1) to investigate psychometric properties of a new questionnaire (SAPE, Scales of the Attitudes toward People with Epilepsy) that assesses attitudes toward people with epilepsy (PWE) (2) to compare the effects of mode of survey administration (web-based vs. face-to-face) on attitudes, and (3) to identify predictors of attitudes. METHODS: A face-to-face and a web-based survey were performed in Germany. Weighting factors were used to achieve representative samples of the German population. Reliability and validity of the 6 scales of the SAPE (social distance, stereotypes, personal concerns, and emotional reactions differentiated by fear, anger, and pity) were evaluated and compared for both surveys. Epilepsy knowledge was also assessed. General linear models were performed to investigate predictors of attitudes toward PWE including the type of survey. RESULTS: In total, 1001 participants of the web-based survey and 1026 participants of face-to-face survey were included. Psychometric analyses indicated satisfactory reliability and validity of the scales and differed only slightly between modes of survey. In both surveys, fears and concerns were more pronounced than stereotypes and social distance. However, mean values of two scales were slightly or moderately higher in the face-to-face survey indicating more negative attitudes toward PWE (p < 0.001). Fewer participants of the face-to-face survey reported personal experience with PWE, claiming to know what to do in case of a seizure and claiming to know that seizures can be treated successfully (p < 0.001). These variables proved to be important predictors of positive attitudes toward PWE, besides demographic factors (e.g. age < 65, female gender). When controlling for them, the differences remained significant only for the scales Social Distance (moderately) and Fear (slightly). SIGNIFICANCE: In total, psychometric analyses show that web-based surveys using the SAPE may be an alternative to face-to-face surveys to assess attitudes toward PWE. This applies also to the scales Social Distance and Emotional Reactions that allow comparisons with other diseases, e.g. psychiatric disorders. Most scales differ only slightly between survey modes, except social distance. This indicates that single components of attitudes toward PWE may be dependent on the mode of survey or different characteristics of respondents.

Long-term treatment with everolimus in TSC-associated therapy-resistant epilepsies.

PURPOSE: To investigate the efficacy and tolerability of long-term treatment with Everolimus (EVO) in patients with tuberous sclerosis complex (TSC) and therapy-resistant epilepsy in a compassionate use trial. METHODS: After a 3-month baseline, patients were treated with EVO. Treatment was divided into treatment phases each lasting at least 9 months. Patients started with one of three target serum levels. In case of insufficient seizure control, subsequent treatment phases with other target serum levels followed. The accompanying antiseizure medication (ASM) remained stable during the baseline phase and for at least the initial three treatment phases. We evaluated changes in seizure frequency and seizure-free days compared to baseline for each patient (Cox-Stuart-test). RESULTS: Fifteen patients were followed up for up to 10 years (minimum 0.6 years, median 5.8 years). Twelve patients (80%) experienced a significant reduction in seizure frequency or an increase in seizure-free days: Six (40%) patients became seizure-free and four patients (26.7%) remained seizure free for > 7 years, of which three required no additional ASM. All participants reported at least one adverse effect, the vast majority (92.5%) of which were mild or moderate. CONCLUSION: Long-term treatment with EVO was highly efficacious, safe and well tolerated. While EVO can be a therapeutic option for therapy-resistant epilepsy in TSC, it can take a long time for seizure relief to manifest.

Epilepsy associated with tuberous sclerosis complex in childhood: Long-term outcome in children after epilepsy surgery and children non-eligible for epilepsy surgery.

OBJECTIVE: Drug-resistant epilepsy is one of the major disease burdens in patients with tuberous sclerosis complex (TSC). Epilepsy surgery has been shown to be effective in TSC, but making a decision for surgery is often more complex than in other surgically amenable epilepsy syndromes and not all patients with TSC are eligible. We investigated long-term outcomes (after ≥one year; median, 6.4 years) with a special interest in general developmental level, health-related quality of life, parental concerns due to epilepsy, impact on family, and social adaptation in children who underwent epilepsy surgery and in children who were not eligible for surgery. METHODS: Eighty-five children (median age at intervention: 3.3 years, interquartile range [IQR]: 1.8-6.3 years) with TSC-related epilepsy had a presurgical investigation, and 34 of this group underwent epilepsy surgery. At follow-up (median age: 11.5 years, IQR: 7.8-15.5 years), we assessed seizure outcome, health-related quality of life, social adaptation, parental concerns due to epilepsy, and general developmental level based on established questionnaires and a standardized interview. Generalized linear models were performed for statistical evaluation. RESULTS: At follow-up, 53% (18/34) of the operated patients were seizure free for ≥12 months and 30% (15/50) of the patients non-eligible for epilepsy surgery (p = 0.037). In the surgical group, developmental level was significantly higher in seizure-free patients, in comparison to non-seizure-free patients (p = 0.004); this was also observed in the non-surgical group, but less marked (p = 0.089). Furthermore, developmental level was significantly (p ≤ 0.001) related to quality of life, social adaptation, impact on family, and parental concerns. In both cohorts, parental concerns were less pronounced if children became seizure free (p < 0.001 and p = 0.018, respectively). SIGNIFICANCE: In children with TSC-related epilepsy, quality of life, social adaptation, and impact on family were related to general developmental level, which in turn was significantly related to seizure freedom. Consequent epilepsy management aiming at seizure freedom, including presurgical evaluation and, if indicated, epilepsy surgery in a center specifically experienced with TSC-related epilepsy, is a worthwhile effort to improve quality of life in patients with TSC and their families.

Incidence, characteristics and risk factors for perioperative cardiac arrest and 30-day-mortality in preterm infants requiring non-cardiac surgery.

STUDY OBJECTIVE: To determine 30-day-mortality, incidence and characteristics of perioperative cardiac arrest as well as the respective independent risk factors in preterm infants undergoing non-cardiac surgery. DESIGN: Retrospective observational Follow-up-study. SETTING: Bielefeld University Hospital, a German tertiary care hospital. PATIENTS: Population of 229 preterm infants (age < 37th gestational week at the time of surgery) who underwent non-cardiac surgery between 01/2008-12/2018. MEASUREMENTS: Primary endpoint was overall 30-day-mortality. Secondary endpoints were the incidence of perioperative cardiac arrest and identification of independent risk factors. We performed univariate and multivariate analyses and calculated odds ratios (OR) for risk factors associated with these endpoints. MAIN RESULTS: 30-day-mortality was 10.9% and perioperative mortality 0.9%. Univariate risk factors for 30-day-mortality were perioperative cardiac arrest (OR,12.5;95%CI,3.1 to 50.3), comorbidities of lungs (OR,3.7;95%CI,1.2 to 11.3) and gastrointestinal tract (OR,3.5;95%CI,1.3 to 9.6); sepsis (OR,3.6;95%CI,1.4 to 9.5); surgery between 22:01-7:00 (OR,7.3;95%CI,2.4 to 21.7); emergency (OR,4.5;95%CI,1.6 to 12.4); pre-existing catecholamine therapy (OR,5.0;95%CI,2.1 to 11.9). Multivariate logistic regression indicated that perioperative cardiac arrest (OR,13.9;95%CI,2.7 to 71.3), low body weight (weight < 1000 g: OR,26.0;95%CI,3.2 to 212; 1000-1499 g: OR,10.3; 95%CI,1.1 to 94.9 compared to weight > 2000 g), and time of surgery (OR,5.9;95%CI,1.6 to 21.3) for 22:01-7:00 compared to 7:01-15:00) were the major independent risk factors of mortality. Incidence of perioperative cardiac arrests was 3.9% (9 of 229;95%CI,1.8 to 7.3). Univariate risk factors were congenital anomalies of the airways (OR,4.7;95%CI,1.2 to 20.3), lungs (OR,4.7;95%CI,1.2 to 20.3) and heart (OR,8.0;95%CI,2 to 32.2), pre-existing catecholamine therapy (OR,59.5;95%CI,3.4 to 1039), specifically, continuous infusions of epinephrine (OR,432;95%CI,43.2 to 4318). CONCLUSIONS: 30-day-mortality and the incidence of perioperative cardiac arrest of preterms undergoing non-cardiac surgery were higher than previously reported. The identified independent risk factors may improve interdisciplinary perioperative risk assessment, optimal preoperative stabilization and scheduling of optimal surgical timing.

Therapeutic Drug Monitoring of Lamotrigine, Lacosamide, and Levetiracetam in Dried Capillary Blood-Determination of Conversion Factors for Serum-Based Reference Ranges.

BACKGROUND: Drug concentrations of antiepileptic drugs (AEDs) are routinely determined from blood serum or plasma at trough levels (before intake of morning dose). In capillary blood collection, blood is taken from the fingertip with the aid of a disposable tool and dried on absorbent material. The volumetric absorptive microsampling technique offers several advantages over the use of filter paper cards. The aim of this study was to determine conversion factors for the estimation of AED serum concentrations from capillary blood concentrations. METHODS: Venous and capillary blood samples were collected from adult inpatients with epilepsy who were treated with lacosamide (LCM, n = 30), lamotrigine (LTG, n = 40), and/or levetiracetam (LEV, n = 36). A validated liquid chromatography-mass spectrometry (LC-MS) method for dried blood samples for these AEDs was compared with routine serum laboratory methods. Method agreement was evaluated using different regression techniques, and the conversion factors were calculated. RESULTS: Regression analyses revealed a linear relationship between serum and capillary blood concentrations for all 3 AEDs (r ≥ 0.95). For LTG, the regression intercept was significantly different from 0, indicating that the relationship was linear, but not necessarily proportional. Although LEV and LCM concentrations tended to be lower in capillary blood than in serum (mean ratio of serum concentration to capillary blood concentration: 1.14 and 1.22, respectively), LTG concentrations were higher in capillary blood (mean ratio = 0.85). CONCLUSIONS: The estimation of serum concentrations from measured capillary blood concentrations is feasible for LCM, LTG, and LEV. A simple ratio approach using the mean ratio and Passing-Bablok regression showed the best results for all 3 AEDs. The volumetric absorptive microsampling technique facilitates the quantitative sample collection of capillary blood and overcomes the drawbacks associated with the classical dried blood spot technique.

Effects of a specialized inpatient treatment program on epilepsy-related impairments of patients with epilepsy and intellectual disability as rated by relatives and professional caregivers.

INTRODUCTION: The aim of the study was to determine the impact of a comprehensive inpatient treatment program for persons with epilepsy and intellectual disability (ID) on the concerns of relatives and caregivers, quality of life (QoL), and global health and clinical aspects, assessed by a questionnaire for relatives and caregivers. METHODS: We performed an open, controlled pre/post study in inpatients with epilepsy and ID or acquired brain damage treated for at least 14 days in a tertiary referral center for epilepsy. Questionnaires were administered to relatives/professional caregivers shortly before admission and 6 months after discharge for the treatment group (TG). The control group (CG) was recruited from the waiting list; questionnaires were answered at the time of application for treatment and 3-6 months later. The questionnaire was the GEOS-43G, the German version of the Glasgow Epilepsy Outcome Scale (GEOS-35), which was extended by eight additional questions from the GEOS-90. Furthermore, QoL, global health, and clinical aspects were assessed using a short questionnaire. Generalized estimation equations (GEEs) were used for statistical analyses. RESULTS: One-hundred and eight subjects were evaluable in the TG, and 90 in the CG. Concerns about seizures, injuries/risks, medical treatment, diagnostic issues, and the GEOS-43G total score decreased significantly in the TG in contrast to the CG. For the TG, improvements were also significant for global QoL, global health, efficacy, tolerability of AEDs, and for seizure frequency. Caregivers reported larger improvements compared to relatives. CONCLUSION: The evaluation of the relatives and caregivers in our study indicates that inpatient treatment in a specialized center with a dedicated multi-professional program led to significant improvements regarding the concerns of relatives or caregivers, and in the QoL and related aspects in persons with epilepsy and ID. This shows that specialized inpatient treatment may be helpful for persons with epilepsy and ID.

Impact of a toothpaste with microcrystalline hydroxyapatite on the occurrence of early childhood caries: a 1-year randomized clinical trial.

The aim of this trial was to determine whether a toothpaste with microcrystalline hydroxyapatite is not inferior to a fluoride toothpaste in prevention of caries in children. This double-blinded randomized control trial compared two toothpastes regarding the occurrence of caries lesions using International Caries Detection and Assessment System (ICDAS) ≥ code 1 on the primary dentition within 336 days. The test group used a fluoride-free hydroxyapatite toothpaste three times daily while control group used a toothpaste with fluoride. 207 children were included in the intention-to-treat analysis; 177 of them finished the study per protocol. An increase in caries ICDAS ≥ code 1 per tooth was observed in 72.7% of the hydroxyapatite-group (n = 88), compared with 74.2% of the fluoride-group (n = 89). The exact one-sided upper 95% confidence limit for the difference in proportion of participants with ICDAS increase ≥ 1 (-1.4%) was 9.8%, which is below the non-inferiority margin of 20% demonstrating non-inferiority of hydroxyapatite compared to the fluoride control toothpaste. This RCT showed for the first time, that in children, the impact of the daily use of a toothpaste with microcrystalline hydroxyapatite on enamel caries progression in the primary dentition is not inferior to a fluoride control toothpaste (Clinical Trials NCT03553966).

Correction to: Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome.

The original version of this article unfortunately contained a mistake.

Influence of dose and antiepileptic comedication on brivaracetam serum concentrations in patients with epilepsy.

The aim of this study was to investigate the influence of concomitant antiepileptic drugs (AEDs) on brivaracetam (BRV) trough serum concentrations. A total number of 368 routinely collected blood samples from 148 inpatients from Mara Hospital (Bethel Epilepsy Center) and von Bodelschwingh Foundation Bethel were retrospectively evaluated. Generalized estimation equations (GEEs) were used for statistical analysis. GEE analyses showed that BRV trough serum concentrations were significantly lower in patients with strong enzyme-inducing AEDs (carbamazepine, phenytoin, and/or phenobarbital/primidone, -49%), but were not affected by concomitant intake of oxcarbazepine or eslicarbazepine. Age and gender did not have a significant effect. An alternative GEE model analyzing the BRV level-to-dose ratios yielded comparable results. Our results from routine therapeutic drug monitoring data indicate that the effect of enzyme-inducing AEDs on BRV serum concentrations is stronger than the 20%-30% reduction in BRV exposure previously reported in pharmacokinetics studies. Further research is necessary to evaluate these differences and to elucidate possible clinical consequences.