Search

The K300 Double Pendulum Interferometer is a compact high resolution Fourier Transform spectrometer designed for outdoor optical remote sensing in the infrared spectral region. Apart from the known atmospheric pollution monitoring by long-path measurements and smoke stack remote sensing at power plants, the remote diagnostic of hot aircraft engine emissions is a very interesting application of the infrared spectroscopy. First results of such measurements performed with the Kayser-Threde Double Pendulum Interferometer K300 at the DLR airport, Oberpfaffenhofen on January 15, 1992 are presented and discussed.

RLYB212 is a human monoclonal anti-human platelet antigen (HPA)-1a immunoglobulin gamma 1 in clinical development as a subcutaneous injection for the prevention of maternal alloimmunization to fetal HPA-1a leading to fetal and neonatal alloimmune thrombocytopenia (FNAIT). This analysis developed a target-mediated drug disposition (TMDD) model to simultaneously characterize RLYB212 pharmacokinetics (PK) and HPA-1a-positive platelet dynamics in HPA-1b/b (HPA-1a-negative) volunteers. The model was then used to perform simulations to inform a dosing regimen in a phase II clinical study in pregnant women, where simulations accounted for physiological changes throughout pregnancy. Allometric scaling (0.75) for clearance and intercompartment transfer rate and volume (1) was included in the base model to account for variations in body weight. A 0.06 mg RLYB212 dose with a loading dose of 0.12 mg was identified as the optimal dosing regimen of RLYB212, which maintained exposures below the target upper boundary of ~10 ng/mL throughout pregnancy. This work presents an application of the TMDD model that advances the quantitative clinical pharmacology toolkit to understand monoclonal antibody PK in pregnancy., (© 2024 Rallybio. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Patient and public involvement is vital for high-quality research. Integrating patients' and providers' perspectives early in research enhances the feasibility and relevance of study results. Within our family practice-based research network ForN, we established a standing patient advisory board (PAB) to include patients with diverse conditions and experiences. In this paper, we aim to describe the establishment and functioning of a standing PAB in family medicine research from patients' and researchers' perspectives., Methods: After each PAB meeting, patients and researchers were asked to name anonymously positive and challenging moments in a feedback form with open questions. Researchers were also asked to reflect on how they implemented the discussion content in their research projects. The responses from both groups were transferred to MAXQDA 2018 and analyzed separately using thematic analysis., Results: We analyzed 40 feedback forms from patients and 14 feedback forms from researchers. The dominant theme in the patients' feedback was 'exchange': They positively emphasized the 'exciting and open discussions' and the exchange of perspectives with one another and researchers. The clarity of the researchers' presentations and the research topics were appreciated. Researchers also positively highlighted the open atmosphere of the discussions. Presenting their research to the PAB helped most researchers reflect on their research topics from patients' perspectives and implement changes. However, researchers also mentioned several barriers to the implementation of PAB members' feedback., Conclusion: The establishment of a standing PAB in family practice research is feasible and productive both from patients' and researchers' perspectives., Patient or Public Contribution: This study reports the evaluation of the establishment of a standing PAB in family practice research. Board members are involved in the design of studies, the co-production of interventions and information material, and the interpretation of data., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Immunoglobulin G (IgG) replacement therapy is the standard of care for patients with primary immunodeficiencies with antibody deficiencies. Intravenous (IVIG), subcutaneous (SCIG), and hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) therapies differ in their pharmacokinetic (PK) profiles, administration routes, and dosing regimens. Information on use of subcutaneous therapy in IgG treatment-naive patients is limited. This study used population pharmacokinetic (popPK) model-based simulations to characterize IgG PKs in IgG-naive patients with varying disease severity across several IVIG, SCIG, and fSCIG dosing regimens. An integrated popPK model, developed and validated using data from eight clinical trials, was utilized to simulate scenarios that varied by therapy, loading regimen, maintenance dose (equivalent to 400, 600, or 800 mg/kg every 4 weeks [Q4W]), and baseline endogenous total IgG concentration (1.5 or 4.0 g/L). Simulations were performed for age groups of 2-<6, 6-<12, 12-<18, and ≥18 years. Steady-state serum trough IgG concentrations (C min,ss ), proportion of patients achieving C min,ss  ≥ 7 g/L, and days taken to reach this threshold were summarized. SCIG provided greater mean C min,ss values than IVIG and fSCIG for any scenario. Across all therapies, C min,ss tended to increase with age, dose, and endogenous concentration. Although the findings are model-based and not a summarization of real-world observations, doses ≥ 800 mg/kg Q4W with corresponding loading regimens are likely to be clinically appropriate for achieving target IgG concentrations in treatment-naive patients in a timely manner, especially at low endogenous starting concentrations. Therapy-specific dose adjustment based on baseline endogenous IgG concentration, clinical status, and patient characteristics may be warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘ZL is an employee of Takeda Development Center Americas, Inc. and is a Takeda shareholder. KF, EF, and FE are employees of Certara USA and have received research grants from Takeda Development Center Americas, Inc. for this study. LY was an employee of Takeda Development Center Americas, Inc. at the time of the study and is a Takeda shareholder.’., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic kidney disease-associated pruritus (CKD-aP) is an underrated symptom in patients with impaired kidney function. The present study assessed the prevalence, impact on quality of life (QoL) and risk factors for CKD-aP in a contemporary national cohort of patients on haemodialysis. In addition, we evaluated attending physicians' awareness and approach to therapy., Methods: Validated patient's and physician's questionnaires on pruritus severity and QoL were used in combination with information obtained by the Austrian Dialysis and Transplant Registry., Results: The prevalence of mild, moderate and severe pruritus in 962 observed patients was 34.4%, 11.4% and 4.3%. Physicians' estimated prevalence values were 25.0 (95% CI 16.8-33.2), 14.4 (11.3-17.6) and 6.3% (4.9-8.3), respectively. The estimated national prevalence estimate extrapolated from the observed patients was 45.0% (95% CI 39.5-51.2) for any, 13.9% (95% CI 10.6-17.2) for moderate and 4.2% (95% CI 2.1-6.2) for severe CKD-aP. CKD-aP severity was significantly associated with impaired QoL. Risk factors for moderate-severe pruritus were higher C-reactive protein [odds ratio (OR) 1.61 (95% CI 1.07-2.43)] and parathyroid hormone (PTH) values [OR 1.50 (95% CI 1.00-2.27)]. Therapy for CKD-aP included changes in the dialysis regimen, topical treatments, antihistamines, gabapentin and pregabalin and phototherapy in a majority of centres., Conclusions: While the overall prevalence of CKD-aP in our study is similar to that in previously published literature, the prevalence of moderate-severe pruritus is lower. CKD-aP was associated with reduced QoL and elevated markers of inflammation and PTH. The high awareness of CKD-aP in Austrian nephrologists may explain the lower prevalence of more severe pruritus., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Purpose: To assess the pharmacokinetics (PK) of subcutaneous immunoglobulin (SCIG) and hyaluronidase-facilitated SCIG (fSCIG) therapy across body mass index (BMI) and age categories in patients with primary immunodeficiency diseases (PIDD) previously treated with intravenous immunoglobulin (IVIG)., Methods: Using our previously published integrated population PK model based on data from eight clinical trials, simulations were conducted to examine the effects of BMI and age on serum immunoglobulin G (IgG) PK after administration of SCIG 0.15 g/kg weekly or fSCIG 0.6 g/kg every 4 weeks in patients switching from stable IVIG. Patients were assumed to have baseline IgG trough concentrations of 7 g/L (hypothetical protective threshold)., Results: Mean steady-state serum IgG trough values (C min,ss or trough) increased with BMI and age. Mean C min,ss was 18% (SCIG) and 16% (fSCIG) higher in the obese than the healthy BMI group. Pediatric patients aged < 18 years had 8-22% (SCIG) and 4-20% (fSCIG) lower mean C min,ss values than adults, with the youngest group (2- < 6 years) having the lowest C min,ss . All patients across populations maintained C min,ss IgG concentrations of ≥ 7 g/L after switching to SCIG or fSCIG., Conclusion: Both SCIG and fSCIG successfully maintained trough values at or above the hypothetical protective threshold after switching from stable IVIG, irrespective of BMI or age. Differences in trough values between BMI groups and age groups (≤ 22%) may not warrant SCIG or fSCIG dose adjustments based on BMI or age alone; instead, the dosing paradigm should be guided by prior IVIG dose, individual IgG monitoring, and clinical findings., (© 2023. The Author(s).)

Background: Cross-sectoral and interdisciplinary care and case management can contribute to an improved integration of the primary care for patients with geriatric characteristics. Following this approach, the pilot study RubiN (Regional ununterbrochen betreut im Netz / Continuous Care in Regional Networks) implemented a specific geriatric Care and Case Management (CCM) in five certified practice networks of independent physicians in different regions in Germany. As part of the accompanying process-based evaluation of the project, a survey was conducted among general practitioners and other specialists from these networks in order to find out how, in their view, collaboration with case managers can improve medical care of geriatric patients and contribute to closing possible gaps in primary care structures., Methods: The overall project RubiN, which was designed as a pragmatic controlled trial, compared patients from five practice networks where CCM has been implemented (intervention networks), with patients from three networks where the intervention was not taking place (control networks). Physicians of all eight participating practice networks were included in the present survey. The survey was conducted via a self-developed questionnaire., Results: A total of 111 physicians participated in the survey, 76 of whom were part of an intervention network and 35 part of a control network. The calculated response rate was 15.4% (networks reported a total of approx. 720 members). 91,1% of the participants from intervention networks, who had joined RubiN with their patients, reported satisfaction with their collaboration with case managers (n=41 of 45). 87.0% of the physicians from intervention networks stated that care for geriatric patients had improved as a result of their participation in the pilot study (n=40 of 46). When asked about the overall quality of care provided for their geriatric patients, the assessments of participants from intervention networks were more positive than those of the participants from control networks (MV 3.48 vs. 3.27 on a scale of 1=poor to 5=very good). Agreement with whether external case managers could provide certain services was higher among participants from intervention networks compared to participants from control networks. This was the case, in particular, of services related to medical data collection and test procedures. Overall, both comparison groups showed a high level of willingness to delegate tasks to a CCM., Discussion: Delegation of tasks to geriatric case managers seems to be more readily accepted by physicians in intervention networks than by their colleagues from the control networks, especially as regards medical assessment methods and advanced advisory tasks. The results suggest that interventions in this domain were able to convince physicians of the value that case managers can bring to medical practice and help resolve reservations and skepticism. Especially, the implemented CCM seemed to be an effective way of generating geriatric anamnestic data and fostering the flow of general patient-centered information., Conclusion: From the point of view of general practitioners and other specialists participating in the intervention, CCM has been successfully implemented in their practice networks and seems to be a worthwhile approach that will help provide better coordinated and more team-oriented care to their geriatric patients., (Copyright © 2023. Published by Elsevier GmbH.)

Introduction: Adintrevimab is a fully human immunoglobulin G1 extended half-life monoclonal antibody that was developed to have broad neutralization against SARS-CoV, SARS-CoV-2, and other SARS-like CoVs with pandemic potential. Here we report the safety, pharmacokinetics (PK), serum viral neutralizing antibody (sVNA) titers, and immunogenicity results of the first three cohorts evaluated in the first-in-human study of adintrevimab in healthy adults., Methods: This is a phase 1, randomized, placebo-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged ≥ 18-55 years with no current or prior SARS-CoV-2 infection. Participants were randomized 8:2 to adintrevimab or placebo in each of three dose cohorts: adintrevimab 300 mg IM (cohort 1), 500 mg IV (cohort 2), and 600 mg IM (cohort 3). Follow-up was 12 months. Blood samples were taken predose and at multiple time points postdose up to month 12 to assess sVNA, PK, and antidrug antibodies (ADAs)., Results: Thirty participants received a single dose of adintrevimab (n = 24; 8 per cohort) or placebo (n = 6). All except one adintrevimab participant in cohort 1 completed the study. No participants in any treatment arm experienced a study drug-related adverse event. Across adintrevimab-treated participants, 11 (45.8%) experienced at least one TEAE. All but one TEAE were mild in severity, and all were either viral infection or respiratory symptoms. There were no serious adverse events, discontinuations due to adverse events, or deaths. Adintrevimab exhibited a linear and dose-proportional PK profile and extended serum half-life (mean 96, 89, and 100 days in cohorts 1, 2, and 3, respectively). Participants receiving adintrevimab demonstrated dose-dependent increased sVNA titers and breadth across multiple variants., Conclusion: Adintrevimab at doses of 300 mg IM, 500 mg IV, and 600 mg IM was well tolerated in healthy adults. Adintrevimab demonstrated dose-proportional exposure, rapid development of neutralizing antibody titers, and an extended half-life., (© 2023. The Author(s).)

Due to poor results, the German talent identification and development of the German soccer association DFB no longer performs a shooting test since a few years. The aim of this study was to create and validate a new soccer shooting test that allows valid conclusions to be drawn from the shooting quality of youth soccer players about their overall soccer skills. The shooting test was performed with a total of 57 male club players (age: 15.24 ± 0.864 years) from four different teams from the first, second, fifth, and the seventh division of the respective age group (under 15-year-olds until under 17-year-olds). Each subject took one shot at maximum shot speed and eight target shots, measuring accuracy and the shot speed. A multivariable linear regression analysis with forward selection revealed significant values for the variables average shot speed nondominant leg ( p < 0.001) and total score ( p = 0.004; accuracy × speed of every target shot). Based on these two variables, the soccer skills could be derived from the shooting skills of the adolescents in 57.4% of the cases. The study shows the importance of a good technique with the nondominant leg and of the ability to shoot accurately as well as fast simultaneously.

Plasma-derived immunoglobulin G (IgG) replacement therapy represents the current standard of care for patients with primary or secondary antibody deficiencies, and includes intravenous (IVIG), subcutaneous (SCIG) and facilitated subcutaneous (fSCIG) immunoglobulin products. A holistic understanding of the pharmacokinetics (PK) of IgG for these therapies is key to optimizing their clinical use. We developed an integrated population PK model using non-linear mixed-effects modeling based on data from eight clinical trials (each ≥ 1 year duration; n = 384 patients), which simultaneously characterized IgG PK profiles of IVIG, SCIG or fSCIG in patients with primary immunodeficiencies and identified covariate effects. The final model was a two-compartment turnover model incorporating: the endogenous production of IgG with linear subcutaneous absorption and a product effect on bioavailability; additive and proportional error; between-patient variability on clearance and central volume of distribution; and allometric scaling with lean body mass on clearance, intercompartmental clearance and central and peripheral volumes of distribution. Overall, the model adequately described IgG PK profiles, with residual standard error values < 28 % for all PK parameters. Goodness-of-fit plots and prediction-corrected visual predictive checks indicated a good fit of the observed IgG PK profiles. This integrated PK model has enabled a comprehensive understanding of IgG PK profiles for various immunoglobulin products, and will provide a framework for future investigations of IgG PK with different dosing regimens and in special or wider patient populations of interest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: In Germany, children with life-limiting conditions and complex symptoms are eligible for specialised outpatient palliative care (SOPC). In the federal state of Hesse, SOPC for children (SOPPC) is delivered by teams with paediatric expertise. While burdened by the life-limiting condition of their child, parents must also fulfill their roles as main care providers and decision makers. Collaboration between parents and SOPPC teams is important, as the intermittent care and uncertainty it entails often lasts for several months or years. We explored parents' experiences and their demands of collaboration with SOPPC teams., Methods: We conducted nine narrative interviews with 13 parents of children and adolescents with life-limiting conditions and used a grounded theory approach to analyse interview data., Results: Parents stressed the importance of paediatric expertise, honesty, psychosocial support, an individualised approach, experience of self-efficacy and the need to be recognised as experts for their children. The narrative interviews showed that collaboration between parents and SOPPC teams was characterised by parents' need for specialised professional assistance and their simultaneous empowerment by SOPPC teams., Conclusions: Parents' perceptions of what good collaboration with SOPPC teams entails are manifold. To meet these complex needs, SOPPC requires time and specialised expertise., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: At the onset of the COVID-19 pandemic general practitioners complained about feeling uninformed and lacking a sufficient flow of information from the local health authorities. Secure instant messaging describes a digital, chat-based form of communication enabling ambulatory care providers to connect in real-time and share information across medial sectors. KomPan, a proof-of-concept study, established a secure instant messaging structure in two model regions in Germany to improve communication between general practitioners and local health authorities via an additional communication pathway. This paper presents results of a qualitative user survey., Methods: We recruited general practitioners (n = 43) and staff of local health authorities (n=10) in two Hessian model regions for using the secure instant messaging (SIM) app of the Famedly GmbH, starting in December 2020 (2 nd COVID-19 wave). We asked participants to share their usage experiences after a usage time of multiple months. In guided telephone interviews, we primarily asked how communication between the two user groups had changed while using secure instant messaging. The interviews were transcribed verbatim and analysed using thematic analysis., Results: We conducted ten interviews with general practitioners and two with staff of the participating local health authorities. Using our SIM-based platform promoted professional exchange between general practitioners. In contrast, the app had little impact on communication between local health authorities and general practitioners. Opposing expectations and usage patterns of the two user groups, among other reasons, probably led to a reduced direct trans-sectoral communication via secure instant messaging., Conclusion: Establishing local chat groups for general practitioners was welcomed, especially during the pandemic situation, to improve professional exchange while experiencing challenging working conditions. To use secure instant messaging effectively for trans-sectoral communication a more comprehensive approach seems to be needed, such as digitalisation of institutional communication structures and improved networks of local healthcare providers., (Copyright © 2022. Published by Elsevier GmbH.)

Background and Aim: Children and adolescents with life-limiting conditions and complex symptoms are eligible for specialized outpatient palliative care (SOPC). The SOPC guideline in Germany solely states: "The special needs of children and adolescents shall be considered." This study aims to identify these special needs and to develop recommendations for a revision of the SOPC guideline., Methods: We used a sequential mixed-methods design including surveys, qualitative interviews, participant observations, and focus group discussions with relatives, patients, and team members of the SOPC in Hesse, Germany. Furthermore, we analyzed documentation data of the Hessian SOPC teams., Results: Children and adolescents in SOPC suffer from complex and often rare diseases. They need elaborate palliative care delivered by a team with pediatric expertise. SOPC must include the whole family and coordinate healthcare providers that are stretched regionally. Furthermore, patients and relatives need elaborate psychosocial care. SOPC for children and adolescents is less well-known than SOPC for adults, and access for families is often difficult. There is a healthcare gap for children and adolescents with life-limiting diseases who need palliative care at home but not of the intensive kind provided by SOPC., Conclusions: SOPC for children, adolescents, and adults who have been diseased since their childhood and adolescence must be delivered within an independent structure, including a reimbursement scheme that takes the special care efforts for this patient group into consideration., (© 2022. The Author(s).)

Introduction: VIS649 (sibeprenlimab), a humanized IgG 2 monoclonal antibody that inhibits APRIL, is being developed as a potential treatment for IgA nephropathy (IgAN). This phase 1, first-in-human, randomized, double-blind, single ascending dose study aimed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of VIS649 in healthy adults., Methods: Participants were randomized to VIS649 (sequential i.v. dosing cohorts: 0.5, 2.0, 6.0, 12.0 mg/kg) or placebo; a further cohort received VIS649 6.0 mg/kg or placebo followed by a tetanus/diphtheria vaccine challenge., Results: A total of 51 participants were randomized, dosed, and analyzed for safety (7 for each VIS649 dose; 8 for placebo; 10 for VIS649 + vaccine; 5 for placebo + vaccine). There were no serious adverse events (AEs) or AEs leading to study discontinuation. VIS649 had nonlinear PK: half-life increased with dose and drug exposure increased in a greater than dose-proportional manner. Serum APRIL, IgA, galactose-deficient (Gd) IgA 1 , IgG, and IgM were reversibly suppressed in a dose-dependent manner, with a dose-response in time to recovery. Tetanus and diphtheria serum IgG titers increased after recall vaccination., Conclusion: VIS649 was safe, well tolerated, and reversibly suppressed APRIL and various immunoglobulins, without loss of antigen-specific vaccination response. Further clinical development of VIS649 for IgAN is warranted. Trial registration: ClinicalTrials.gov: NCT03719443., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Background: The health care situation of geriatric patients is often multifaceted, complex and often overlaps with social living conditions. Due to the lack of cross-sectoral and interprofessional health care geriatric patients often, receive insufficient care. Only a holistic view enables a comprehensive evaluation of the complex health risks, but also the potential to preserve the health of geriatric patients. The implementation of cross-sectoral, multi-professional case management could reduce the gaps in care, improve the autonomy of the geriatric patients in their own homes, and allow them to retain it as long as possible. The "RubiN" project examines the effects of multi-professional, cross-sectoral and assessment-based case management on the quality of the care of geriatric patients. The results of the study aim to show whether geriatric patients receive better care using case management than patients who receive standard health care. In addition, data on the effects of case management on practices of general practitioners (GP), the satisfaction with the care concept amongst the case managers, patients and relatives will be collected. Furthermore, a health economic analysis will be carried out., Methods: The project is designed as a prospective controlled study and compares geriatric patients from practice networks in different regions in Germany. Inclusion criteria are: Age ≥ 70 years and care requirements from two different care complexes (identified with the screening instrument 'Angelina'-questionnaire). The intervention is the use of a geriatric case management, where health care is organised based on patient-specific care requirements. Five practice networks of physicians will implement the intervention (n = 3200 patients) and three practice networks will serve as the control group (n = 1200 patients). The primary endpoint is the ability to manage activities of daily living, measured using the Barthel Index. The patients in the intervention group receive geriatric case management and the patients in the control networks receive standard care ("care as usual"). The analysis of the primary data, which is pseudonymised, occurs according to the intention-to-treat principle. For this purpose, the endpoints will be analysed using a group comparison after 12 months. For the health economic analysis, secondary data from the statutory health insurance providers will be included in the analysis, in addition to the primary data. Data for the analysis of the effects the concept has on the GP practices as well as on the satisfaction of the project participants will be collected with questionnaires and interviews with experts., Discussion: The implementation of cross-sectoral and interdisciplinary geriatric case management has been a topic of discussion for years, whereby positive effects have already been-shown. This planned study will be the first evaluation of the effect of case management for geriatric patients with a very large sample. In addition, the effects of case management on the GP practices and also on the relatives of the geriatric patients will be shown. It is intended that the study results pave the way for a widespread implementation of this concept., Trial Registration: German Clinical Trials Register, ID: DRKS00016642 . Registered on 29 October 2019 - Retrospectively registered.

Background: Guidelines on pediatric palliative care recommend to provide care for children and adolescents with life-limiting conditions at home. Since 2007, in Germany, palliative home care can be provided by specialized outpatient palliative care teams. However, teams with specific expertise for children are not available all over the country. Families without this support need to use the hospital to get specialists' assistance. Objective: To explore how parents of children and adolescents with life-limiting conditions think about the hospital as place of care. Design: We conducted narrative interviews with parents and analyzed these by using a grounded theory approach. Setting/Subjects: We interviewed 13 parents (4 fathers and 9 mothers) of 9 children with life-limiting conditions receiving or having received pediatric specialized outpatient palliative care (SOPPC) in Germany. Results: Parents reported feelings of vulnerability, heteronomy, and disablement associated with hospital care and were afraid that their children's needs were not adequately addressed. These perceptions resulted from hospitals' standardized care structures and over- and undertreatment, a lack of continuity of care, hospital pathogens, a lack of a palliative mindset, insensitive hospital staff, the exclusion of parents from the treatment and parental care of their children, the hospital stay as a permanent state of emergency, and a waste of limited life time. Conclusion: Pediatric hospital staff needs training in identifying and responding to palliative care needs. SOPPC structures should be expanded all over Germany to meet the needs of families of children with life-limiting conditions.

IgA nephropathy (IgAN) is the most prevalent primary chronic glomerular disease for which no safe disease-specific therapies currently exist. IgAN is an autoimmune disease involving the production of autoantigenic, aberrantly O-glycosylated IgA1 and ensuing deposition of nephritogenic immune complexes in the kidney. A Proliferation Inducing Ligand (APRIL) has emerged as a key B-cell-modulating factor in this pathogenesis. Using a mouse anti-APRIL monoclonal antibody (4540), we confirm both the pathogenic role of APRIL in IgAN and the therapeutic efficacy of antibody-directed neutralization of APRIL in the grouped mouse ddY disease model. Treatment with 4540 directly translated to a reduction in relevant pathogenic mechanisms including suppressed serum IgA levels, reduced circulating immune complexes, significantly lower kidney deposits of IgA, IgG and C3, and suppression of proteinuria compared to mice receiving vehicle or isotype control antibodies. Furthermore, we translated these findings to the pharmacological characterization of VIS649, a highly potent, humanized IgG2κ antibody targeting and neutralizing human APRIL through unique epitope engagement, leading to inhibition of APRIL-mediated B-cell activities. VIS649 treatment of non-human primates showed dose-dependent reduction of serum IgA levels of up to 70%. A reduction of IgA + , IgM + , and IgG + B cells was noted in the gut-associated mucosa of VIS649-treated animals. Population-based modeling predicted a favorable therapeutic dosing profile for subcutaneous administration of VIS649 in the clinical setting. Thus, our data highlight the potential therapeutic benefit of VIS649 for the treatment of IgAN., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: VIS410, a broadly neutralizing monoclonal antibody that binds the hemagglutinin stem of influenza A viruses, was safe and efficacious in a human H1N1 virus challenge study. This study evaluated the safety and tolerability of VIS410 in non-hospitalized adult patients with uncomplicated influenza A., Methods: Patients 18 to 65 years of age with symptom onset within 72 h were randomized 1:1:1 to receive a single intravenous infusion of VIS410 4000 mg, 2000 mg, or placebo. Neuraminidase inhibitor therapy was prohibited. Treatment-emergent adverse events (TEAEs) were evaluated up to 100 days post-infusion. Influenza symptoms were assessed daily for 10 days using the FLU-PRO tool. Nasopharyngeal virus shedding was assessed by quantitative reverse-transcription PCR (qRT-PCR) and viral culture through Day 7., Findings: Of the 150 patients randomized, 148 received study drug, and 138 were confirmed influenza A positive. Median age was 42 years; median time from symptom onset to treatment was 42 h; 93% had influenza A subtype H3N2., Safety: TEAEs, most commonly diarrhea of mild severity, were dose-related, occurring in 55%, 35%, and 24% of the 4000 mg, 2000 mg, and placebo patients, respectively. Two serious adverse events occurred, both in placebo patients., Symptom Analyses: Baseline FLU-PRO symptom scores were balanced among groups. Mean scores were lower by Days 3 and 4 in the pooled VIS410 treatment group versus placebo (p < 0.023), with a tendency toward faster resolution by Kaplan-Meier analysis., Virology Analyses: VIS410 was associated with reduced median nasopharyngeal viral load TCID 50 AUC Day7 (days × log 10 TCID 50 /mL) (3.66 pooled VIS410 vs 4.78 placebo, p = 0.08) and in the subset of patients with baseline hemagglutination inhibition (HAI) titer ≤40 (overall, 74% of patients) was significantly reduced vs placebo (4.218 pooled VIS410 vs 6.152 placebo, p = 0.009). Kaplan-Meier estimated time to resolution of viral shedding was reduced (1.9 vs 3.6 days, p = 0.03) in VIS410 treated patients. There was a trend toward greater proportion of culture-negative patients by Day 3 (66.7% vs 51.1%, p = 0.11); when this analysis was limited to the subset of patients with positive baseline cultures, this difference became more pronounced (63.2% vs 42.5%, p = 0.053). No differences were observed in nasopharyngeal influenza qRT-PCR profiles, which represent both live and neutralized virus., Interpretation: VIS410 was safe and well tolerated in adults with uncomplicated influenza A, with favorable effects on symptom resolution and virus replication., Trial Registration: Clinical Trials: NCT02989194., Funding: This project was funded in part with Federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under Contract No. HHSO100201500018C., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)