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• Despite emerging evidence, oral benzodiazepines with unsuitable pharmacokinetics for treatment of prolonged seizures remain widely used. • A substantial proportion of patients (28.0 %, n = 35) reports inappropriate use, administering medication after every seizure. • Almost half (46.0 %) of patients with continuing seizures have no access to rescue medication, this might indicate a lack of adequate therapy of seizure emergencies. • On average, rescue medication prescription occurred 7.1 years after epilepsy diagnosis. Seizure clusters, prolonged seizures, and status epilepticus are life-threatening neurological emergencies leading to irreversible neuronal damage. Benzodiazepines are current evidence-based rescue therapy options; however, recent investigations indicated the prescription of mainly unsuitable benzodiazepines and inappropriate use of rescue medication. To examine current use, satisfaction, and adverse events concerning rescue medication in patients with epilepsy in Germany. The study was conducted at epilepsy centres in Frankfurt am Main, Greifswald, Marburg, and Münster between 10/2020 and 12/2020. Patients with an epilepsy diagnosis were assessed based on a questionnaire examining a 12-month period. In total, 486 patients (mean age: 40.5, range 18–83, 58.2 % female) participated in this study, of which 125 (25.7 %) reported the use of rescue medication. The most frequently prescribed rescue medications were lorazepam tablets (56.8 %, n = 71 out of 125), buccal midazolam (19.2 %, n = 24), and rectal diazepam (10.4 %, n = 13). Seizures continuing for over several minutes (43.2 %, n = 54), seizure clusters (28.0 %, n = 35), and epileptic auras (28.0 %, n = 35) were named as indications, while 28.0 % (n = 35) stated they administered the rescue medication for every seizure. Of those continuing to have seizures, 46.0 % did not receive rescue medication. On average, rescue medication prescription occurred 7.1 years (SD 12.7, range 0–66) after an epilepsy diagnosis. Unsuitable oral benzodiazepines remain widely prescribed for epilepsy patients as rescue medication. Patients also reported inappropriate use of medication. A substantial proportion of patients who were not seizure-free did not receive rescue medication prescriptions. Offering each patient at risk for prolonged seizures or clusters of seizures an individual rescue treatment with instructions on using it may decrease mortality and morbidity and increase quality of life.. [ABSTRACT FROM AUTHOR]

Across Europe, there are differences regarding driving restrictions for patients with epilepsies and seizures. In the light of increasing mobility, knowledge about those different regulations is of high importance for counseling patients, and physicians. A structured online survey was sent to the official representatives of the different European ILAE chapters, asking for the local driving restrictions for patients with epilepsies, first seizures, syncopes, and psychogenic non-epileptic seizures. The survey was sent to 38 chapters or representatives of 47 European Countries. 33 chapters answered. The majority of countries require 1 year of seizure-freedom for the ability to drive (Group 1, former categories A, B, B + E, F, G. H, K, L, and P; driving license which authorizes its holder to drive vehicle classes categories of the motor vehicle), usually with the need to continue antiseizure medication (ASM). Some countries have much stricter regulations before allowing for driving. Legal regulations after a first unprovoked seizure differ between 6 months for Group 1 license holders in most European countries, and one year in Luxembourg and Malta. In Serbia, there is no legal regulation for this special situation. The situation after a first seizure is even more complex for Group 2 license holders (former categories C1, C1+E, C, C + E, D1, D1+E, D, D + E). Knowledge of the different recommendations of the individual European countries is of high relevance in the counseling of epilepsy patients. Europe-wide regulations, e.g. following the IBE-recommendations are needed to facilitate the patients' situation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy.Methods: Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)).Results: Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy.Conclusion: STP seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of STP in adult patients with pharmacoresistant focal epilepsy. [ABSTRACT FROM AUTHOR]

Abstract: Oxyfuel combustion is considered to be an energy efficient process for carbon capture and storage in power plants. Compared to cryogenic air separation, oxygen supply by means of an oxygen transport membrane (OTM) is more energy efficient. This paper describes possible implementations of an OTM into an oxyfuel process, in particular that is three-end and four-end integration of the membrane whereby the focus is put on overall cycle efficiency and possible measures to improve cycle efficiency. Starting from a simple conservative integration of the membrane, several steps for improvement of the process efficiency are shown. With a three-end integration the maximum achievable efficiency is 40.1%, with a four-end integration of the membrane an overall efficiency of 40.7% including CO2 compression with 90% capture can be achieved for a hard coal fired power plant of 1210MWth compared to 45.9% efficiency for a reference power plant without carbon sequestration. In this case the effective energy demand for oxygen production can be reduced to . In a process variant in which the expansion turbine for the oxygen depleted air is co-fired, the combined efficiency reaches 46.1%. Although OTM operation in four-end design is preferable due to higher achievable net efficiencies, OTM operation in three-end design is likely to be technically viable at first since up to now no membrane material is available which withstands contact with flue gas. [ABSTRACT FROM AUTHOR]

Abstract: Background: The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. Objectives: Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. Methods: Study participants were healthy infants aged 15–27 months at the time of booster vaccination. Each participant had received three doses of a DTaP vaccine (Infanrix™, GlaxoSmithKline, Rixensart, Belgium; “reference DTaP”) at age 3, 4, and 5 months as part of a previous clinical trial. More than 20,000 children were eligible for participation in the current study protocol at the time. In a first phase at a University hospital-based vaccination study center, nine sequential cohorts of 63–119 study subjects received one of nine different candidate vaccines. Patients and study personal were blinded with regard to which vaccine was currently in use. Reactogenicity was solicited from parents using diary cards. Blood was drawn prior to and 4 weeks after vaccination and immediately centrifuged. The serum was stored at −20°C until serology was performed by ELISA tests. As soon as the first candidate vaccine with adequate reactogenicity and immunogenicity profile was identified in the first study phase, a second study phase was initiated in parallel, to evaluate the safety and reactogenicity of the respective candidate vaccine in private practices in large cohorts (1613–2095 study subjects per group). Results: In the first study phase, DTaP with no aluminum induced the highest frequency of ETS and fever. All other candidate vaccines caused lower rates of local and general reactions than the reference DTaP. As a general rule, vaccines with less antigen induced fewer reactions, although there was no strict dose-response effect and the difference, e.g. between a one-tenth and a one-fifth DTaP dose (DTaP 1/5; DTaP 1/10) was not clinically relevant. Separate injections of Td and aP caused fewer general reactions than the respective TdaP combination and local reactions were higher at the aP than at the Td injection site. Again, as a general rule, reduced amounts of antigen induced lower antibody concentrations, although all vaccines induced “protective” anti-tetanus and anti-diphtheria antibody responses. A total of 92–100% of children showed seroresponses to pertussis antigens even when vaccinated with reduced amounts of the respective pertussis antigen. Elimination of aluminum from DTaP vaccine induced higher anti-tetanus-antibody concentrations and so did a reduction of the amount of diphtheria antigen. Additional examples for antigen interaction were increased antibody concentrations, observed with injection of Td and aP into different limbs. In the second study phase, all three vaccines evaluated (one with a reduced amount of diphtheria antigen, TdaP; one with reduced amounts of all antigens, tdap; and one with a fifth dose of the reference vaccine (DTaP 1/5)) were safe and had an acceptable reactogenicity profile in a total of 4871 study subjects. Conclusions: Local reactions due to DTaP booster doses in the second year of life can be reduced by reducing the amount of antigen in the respective vaccine while an adequate immunogenicity is maintained. Aluminum-free vaccines induced ETS and fever most commonly. Any changes in vaccine composition should lead to a full evaluation of the new product. [Copyright &y& Elsevier]

Abstract: Background: To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods: Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus-H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. Results: Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41IU/mL; Control, 5.78IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever ≥38.0°C following each vaccination was reported more frequently in the PCV7 group (28.3–50.0%) than in the Control group (15.6–33.6%) whereas fever >39.0°C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8–2.7%; Control, 1.6–4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. Conclusion: DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12–15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children. [Copyright &y& Elsevier]

Abstract: The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0–6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Δcpm=14173cpm) response. [Copyright &y& Elsevier]

The characteristics of the IgA plasma cell neoplasms are not clearly reported in the literature. The main goal of this study is to examine IgA plasma cell neoplasms (PCN) and to compare them to IgG lesions. After at least 5 years from the identification of an M protein, 98 cases were selected, the presentation and clinical evolution of 45 IgA neoplasms were compared to 43 cases of IgG gammopathies. The classification at presentation as monoclonal gammopathy of undermined significance (MGUS)-22 of 45 IgA and 20 of 43 IgG (49 vs 46%), plasma cell myeloma (PCM)-22 of 45 IgA and 22 of 43 IgG (49 vs 51%) and smoldering PCM (SPCM)-1 each (2% for both) was essentially identical. No solitary plasmacytomas were identified. At presentation, IgA patients were younger (66.5 ± 11.3 vs. 69.2 ± 10.7 years), less likely to have bone lesions (12/45 vs 18/43, p < 0.14) or immunoparesis (51% vs. 63%), differences statistically insignificant. Cases with normal fluorescence in-situ hybridization (FISH) results, 27% for IgA vs 61% for IgG (p < 0.037) were statistically different. The IgA patients had worse survival (80 vs 108 months median IgA vs IgG, p < 0.013), difference not detectable in the first 5 years, but substantial after 10. In conclusion, poorer long-term survival and increased genomic complexity by FISH are characteristics of IgA PCNs. • At presentation IgA cases are similar to IgG cases. • There is no difference in survival of IgA and IgG patients in the first 5 years. • Long-term survival of IgA patients is significantly worse. • By FISH, IgA cases have more abnormalities than IgG cases. [ABSTRACT FROM AUTHOR]

Abstract: Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12–14months) and 268 children (3–5years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1year of age. [Copyright &y& Elsevier]

Abstract: The safety and reactogenicity of a booster dose of GSK Biologicals’ hexavalent DTPa-HBV-IPV/Hib vaccine (N=4725) was compared with the separate administration of GSK Biologicals’ DTPa-IPV/Hib and HBV vaccines (N=4474) in two open, randomized multicenter studies (A and B). Solicited symptoms occurring within 4 days of vaccination were recorded on diary cards and serious adverse events (SAEs) were collected throughout the study period. In Study A (N=1149), incidences of solicited symptoms were similar in both groups; there were no SAEs either reported within 4 days of vaccination or considered to be causally related to vaccination. In study B (N=8050), where fever was the only solicited symptom, rectal temperature ≥39.5°C was observed in 2.5% and 2.8% of the subjects, respectively. Fever ≥40.0°C was rare (0.6%), and only two cases of febrile convulsions were recorded during the 4 days following vaccination both in the control group. Large swelling reactions (defined as local injection site swelling with diameter >50mm, noticeable diffuse injection site swelling or noticeable increased circumference of the injected limb) were reported following 2.3% of the booster vaccine doses, regardless of the vaccine used. Extensive swelling reactions involving an adjacent joint were reported in 0.1% of the subjects. Two SAEs, both reported after booster doses of DTPa-IPV/Hib and HBV vaccines administered separately, were considered by the investigators to be related to vaccination. Both resolved completely without sequelae. The hexavalent DTPa-HBV-IPV/Hib vaccine and the DTPa-IPV/Hib and HBV vaccines administered separately have similar good reactogenicity and safety profiles when given as booster doses in the second year of life. [Copyright &y& Elsevier]

Safety, reactogenicity and immunogenicity of GSK Biologicals’ hexavalent DTPa–HBV–IPV/Hib vaccine (Infanrix®hexa) was assessed when used for primary vaccination at 3, 4 and 5 months of age (N=2163), compared to the separate administration of DTPa–IPV/Hib and HBV vaccines (N=720). A similar safety and reactogenicity profile was demonstrated for both vaccine regimens, as well as a good immune response for all antigen components. By offering protection against six diseases in a series of single injections, the hexavalent DTPa–HBV–IPV/Hib vaccine was shown to be a safe, well tolerated and immunogenic alternative to primary immunization with licensed separately administered vaccines. [Copyright &y& Elsevier]