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Abstract Objective The aims of this study were to translate the SAPE questionnaire (Scales of the Attitudes toward People with Epilepsy) questionnaire developed in Germany that assesses attitudes toward people with epilepsy (PWE) into Japanese and to examine its reliability and validity. Methods We crafted the Japanese version of SAPE (SAPE‐J) by drawing upon the original German version. On May 22nd and 23rd, 2023, we surveyed the general public registered with an online research survey service (Cross Marketing Group Inc., Tokyo, Japan) using an online questionnaire. Inclusion criteria were an age of ≥18 years, sufficient reading and speaking skills in Japanese, and the ability to comprehend the Japanese questionnaires. In addition to the translated SAPE‐J, we asked about knowledge of epilepsy, personal experience with epilepsy, and gathered information about age, gender, employment status, education level, marital status, and household income in accordance with the validation of the German version of the SAPE. Results 400 adults from the general public who had heard or read about epilepsy were asked to participate, granted informed consent, and completed the study questionnaire. The SAPE‐J questionnaire has 6 scales: 1. Social Distance; 2. Stereotypes; 3. Concerns when encountering a person with epilepsy (PWE) and emotional reactions differentiated by 4.1 Fear, 4.2. Anger, and 4.3 Pity; with a total of 26 items. The reliability of these scales ranged between acceptable to high (Cronbach's alpha 0.74–0.92) and confirmatory factor analyses (CFA) confirmed the presumed six‐factor structure of the SAPE (factorial validity). Multivariate generalized linear models (GLM) were used to investigate the construct validity and showed that, depending on subscale, different variables such as age, gender, education level, personal contact to PWE, and epilepsy specific knowledge were significant predictors of attitudes. Significance The Japanese version of the SAPE proved reliable and valid for assessing attitudes toward PWE in the Japanese public. Increasing understanding about how to deal with and accept persons with epilepsy may help reduce negative attitudes and fears about the condition. Plain Language Summary The study translated the German SAPE questionnaire, which measures attitudes toward people with epilepsy (PWE), into Japanese and tested its reliability and validity. The Japanese version (SAPE‐J) was created and surveyed online among 400 adults in Japan. The SAPE‐J has 6 scales covering social distance, stereotypes, and emotional reactions like fear, anger, and pity. Reliability was high (Cronbach's alpha 0.74–0.92), and factor analyses confirmed its structure. The study found age, gender, education, and personal contact with PWE influenced attitudes. The SAPE‐J is reliable and valid for assessing attitudes toward PWE in Japan, potentially reducing negative views and fears about epilepsy.

BackgroundAmerican Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure.MethodsA retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome.Results75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22-24.16).ConclusionsACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes.

(1) Background: The successful treatment of infective endocarditis (IE) relies on detecting causative pathogens to administer targeted antibiotic therapy. In addition to standard microbiological cultivation of pathogens from tissue obtained during heart valve surgery, the potential of molecular biological methods was evaluated. (2) Methods: A retrospective study was performed on heart valve tissue from 207 patients who underwent heart valve surgery for IE. FISHseq (fluorescence in situ hybridization combined with 16S rRNA gene PCR and sequencing) was performed in addition to conventional culture-based microbiological diagnostics. The diagnostic performance of FISHseq was compared with the conventional methods and evaluated in the clinical context. (3) Results: Overall, FISHseq provided a significantly higher rate of specific pathogen detection than conventional valve culture (68.1% vs. 33.3%, p < 0.001). By complementing the findings from blood culture and valve culture, FISHseq was able to provide a new microbiological diagnosis in 10% of cases, confirm the cultural findings in 24.2% of cases and provide greater diagnostic accuracy in 27.5% of cases. FISHseq could identify a pathogen in blood-culture-negative IE in 46.2% of cases, while valve culture provided only 13.5% positive results (p < 0.001). (4) Conclusions: This study demonstrates that using FISHseq as an additional molecular biological technique for diagnostics in IE adds substantial diagnostic value, with potential implications for the treatment of IE. It provides pathogen detection, especially in cases where conventional microbiological cultivation is negative or inconclusive.

Pandoraea spp. are gram-negative, nonfermenting rods mainly known to infect patients with cystic fibrosis (CF). Outbreaks have been reported from several CF centers. We report a Pandoraea spp. outbreak comprising 24 non-CF patients at a large university hospital and a neighboring heart center in Germany during July 2019–December 2021. Common features in the patients were critical illness, invasive ventilation, antimicrobial pretreatment, and preceding surgery. Complicated and relapsing clinical courses were observed in cases with intraabdominal infections but not those with lower respiratory tract infections. Genomic analysis of 15 isolates identified Pandoraea commovens as the genetically most similar species and confirmed the clonality of the outbreak strain, designated P. commovens strain LB-19-202-79. The strain exhibited resistance to most antimicrobial drugs except ampicillin/sulbactam, imipenem, and trimethoprim/sulfamethoxazole. Our findings suggest Pandoraea spp. can spread among non-CF patients and underscore that clinicians and microbiologists should be vigilant in detecting and assessing unusual pathogens.

Objective: To assess the antiviral activity, pharmacokinetics, and safety of MK-6186 in HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI)-naïve, HIV-1-infected male participants. Design: Double-blind, randomized, two-panel study. Methods: In 2 sequential panels, 18 participants received MK-6186 (40 mg [Panel A] or 150 mg [Panel B]) or matching placebo once daily for 7 days. Plasma samples were collected for measurement of HIV-1 RNA levels and MK-6186 pharmacokinetics. Results: For the mean change from baseline in HIV-1 RNA (log10 copies/mL) at 24 h post Day 7 dose, the mean difference (90% confidence interval) between MK-6186 and placebo was −1.54 (−1.73, −1.34) in the 40-mg group and −1.28 (−1.81, −0.75) in the 150-mg group. One participant in the 150-mg group had viral rebound at 24 h after Day 6 dosing (Day 7 predose) associated with outgrowth of the V106A minority variant. Ultra-deep sequencing confirmed expansion of this predose minority variant from 0.26% to 63.67%. No outgrowth or rebound was seen in another participant in whom a V106A minority variant was also detected. MK-6186 was generally well tolerated. MK-6186 was rapidly absorbed with peak concentrations at 2 h followed by a biphasic decline. The effective t½ of MK-6186 was 43.9 to 48.7 h. Steady state was not achieved. Conclusions: Daily monotherapy with MK-6186 demonstrated robust antiviral activity with maximal antiviral activity at a dose of 40 mg. One participant in the 150-mg group exhibited viral rebound with outgrowth of the resistant V106A minority variant, demonstrating a risk of resistance development typical of NNRTIs. The reason for this outgrowth remains unclear as no outgrowth occurred in a participant in the 40-mg group in whom the V106A minority variant was also detected. MK-6186 may be an alternative next-generation NNRTI in combination therapy, in that combination antiretroviral therapy could prevent outgrowth of resistant minority variants. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to translate the SAPE questionnaire (Scales of the Attitudes toward People with Epilepsy) questionnaire developed in Germany that assesses attitudes toward people with epilepsy (PWE) into Japanese and to examine its reliability and validity. Methods: We crafted the Japanese version of SAPE (SAPE‐J) by drawing upon the original German version. On May 22nd and 23rd, 2023, we surveyed the general public registered with an online research survey service (Cross Marketing Group Inc., Tokyo, Japan) using an online questionnaire. Inclusion criteria were an age of ≥18 years, sufficient reading and speaking skills in Japanese, and the ability to comprehend the Japanese questionnaires. In addition to the translated SAPE‐J, we asked about knowledge of epilepsy, personal experience with epilepsy, and gathered information about age, gender, employment status, education level, marital status, and household income in accordance with the validation of the German version of the SAPE. Results: 400 adults from the general public who had heard or read about epilepsy were asked to participate, granted informed consent, and completed the study questionnaire. The SAPE‐J questionnaire has 6 scales: 1. Social Distance; 2. Stereotypes; 3. Concerns when encountering a person with epilepsy (PWE) and emotional reactions differentiated by 4.1 Fear, 4.2. Anger, and 4.3 Pity; with a total of 26 items. The reliability of these scales ranged between acceptable to high (Cronbach's alpha 0.74–0.92) and confirmatory factor analyses (CFA) confirmed the presumed six‐factor structure of the SAPE (factorial validity). Multivariate generalized linear models (GLM) were used to investigate the construct validity and showed that, depending on subscale, different variables such as age, gender, education level, personal contact to PWE, and epilepsy specific knowledge were significant predictors of attitudes. Significance: The Japanese version of the SAPE proved reliable and valid for assessing attitudes toward PWE in the Japanese public. Increasing understanding about how to deal with and accept persons with epilepsy may help reduce negative attitudes and fears about the condition. Plain Language Summary: The study translated the German SAPE questionnaire, which measures attitudes toward people with epilepsy (PWE), into Japanese and tested its reliability and validity. The Japanese version (SAPE‐J) was created and surveyed online among 400 adults in Japan. The SAPE‐J has 6 scales covering social distance, stereotypes, and emotional reactions like fear, anger, and pity. Reliability was high (Cronbach's alpha 0.74–0.92), and factor analyses confirmed its structure. The study found age, gender, education, and personal contact with PWE influenced attitudes. The SAPE‐J is reliable and valid for assessing attitudes toward PWE in Japan, potentially reducing negative views and fears about epilepsy. [ABSTRACT FROM AUTHOR]

(1) Background: The successful treatment of infective endocarditis (IE) relies on detecting causative pathogens to administer targeted antibiotic therapy. In addition to standard microbiological cultivation of pathogens from tissue obtained during heart valve surgery, the potential of molecular biological methods was evaluated. (2) Methods: A retrospective study was performed on heart valve tissue from 207 patients who underwent heart valve surgery for IE. FISHseq (fluorescence in situ hybridization combined with 16S rRNA gene PCR and sequencing) was performed in addition to conventional culture-based microbiological diagnostics. The diagnostic performance of FISHseq was compared with the conventional methods and evaluated in the clinical context. (3) Results: Overall, FISHseq provided a significantly higher rate of specific pathogen detection than conventional valve culture (68.1% vs. 33.3%, p < 0.001). By complementing the findings from blood culture and valve culture, FISHseq was able to provide a new microbiological diagnosis in 10% of cases, confirm the cultural findings in 24.2% of cases and provide greater diagnostic accuracy in 27.5% of cases. FISHseq could identify a pathogen in blood-culture-negative IE in 46.2% of cases, while valve culture provided only 13.5% positive results (p < 0.001). (4) Conclusions: This study demonstrates that using FISHseq as an additional molecular biological technique for diagnostics in IE adds substantial diagnostic value, with potential implications for the treatment of IE. It provides pathogen detection, especially in cases where conventional microbiological cultivation is negative or inconclusive. [ABSTRACT FROM AUTHOR]

Introduction Patients with high-consequence infectious diseases (HCID) are rare in Western Europe. However, high-level isolation units (HLIU) must always be prepared for patient admission. Case fatality rates of HCID can be reduced by providing optimal intensive care management. We here describe a single centre’s preparation, its embedding in the national context and the challenges we faced during the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic. Methods Ten team leaders organize monthly whole day trainings for a team of doctors and nurses from the HLIU focusing on intensive care medicine. Impact and relevance of training are assessed by a questionnaire and a perception survey, respectively. Furthermore, yearly exercises with several partner institutions are performed to cover different real-life scenarios. Exercises are evaluated by internal and external observers. Both training sessions and exercises are accompanied by intense feedback. Results From May 2017 monthly training sessions were held with a two-month and a seven-month break due to the first and second wave of the SARS-CoV-2 pandemic, respectively. Agreement with the statements of the questionnaire was higher after training compared to before training indicating a positive effect of training sessions on competence. Participants rated joint trainings for nurses and doctors at regular intervals as important. Numerous issues with potential for improvement were identified during post processing of exercises. Action plans for their improvement were drafted and as of now mostly implemented. The network of the permanent working group of competence and treatment centres for HCID (Ständiger Arbeitskreis der Kompetenz- und Behandlungszentren für Krankheiten durch hochpathogene Erreger (STAKOB)) at the Robert Koch-Institute (RKI) was strengthened throughout the SARS-CoV-2 pandemic. Discussion Adequate preparation for the admission of patients with HCID is challenging. We show that joint regular trainings of doctors and nurses are appreciated and that training sessions may improve perceived skills. We also show that real-life scenario exercises may reveal additional deficits, which cannot be easily disclosed in training sessions. Although the SARS-CoV-2 pandemic interfered with our activities the enhanced cooperation among German HLIU during the pandemic ensured constant readiness for the admission of HCID patients to our or to collaborating HLIU. This is a single centre’s experience, which may not be generalized to other centres. However, we believe that our work may address aspects that should be considered when preparing a unit for the admission of patients with HCID. These may then be adapted to the local situations.

Abstract Virus biomass outweighs human biomass, and insects biomass outweighs human biomass. Insects are regularly habited by viruses as well as humans, humans are further inhabited via insects. A model of viral flow is described and specified to explain influenza virus seasonality, which, in temperate climate, usually evolves when insects have mostly disappeared. With this hypothesis a coherent description of regular seasonal influenza and other seasonal respiratory virus infections in temperate climates is possible. The incidence of influenza under different circumstances e.g. temperature, humidity, or tropical conditions and different aspects like synchronicity of infections or in respect to evolutionary conditions do sustain this hypothesis if the behaviour of insects is considered.

Background: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure. Methods: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome. Results: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22–24.16). Conclusions: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes. Author summary: American cutaneous leishmaniasis is a skin disease caused by parasites that are transmitted through the bite of sandflies. It is considered as a neglected tropical disease. In non-endemic countries like Germany, this disease is rarely seen and is imported by migrants or travellers who have been infected in tropical or subtropical areas of the Americas. Experts suggest that the treatment should be given depending on the specific parasite species found in the affected skin, but there is still a scarcity of information on the optimal management strategy. We analysed 75 American cutaneous leishmaniasis cases seen between 2000 and 2023 at our German medical centre. Most patients were men, around 35 years of age, who most commonly travelled to the Americas for tourism. We found that when using systemic medications (i.e., given by mouth, injection or drip into a vein), that were recommended for the specific parasite type, patients were more likely to be cured, with a 73% success rate, compared to a mere 35% success rate when those recommendations were not followed. This highlights the importance of identifying the species that is causing the disease, and suggests that tailoring treatment to the specific parasite species increases the chances of cure. [ABSTRACT FROM AUTHOR]

The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1–5 × MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8–40 mg/L and 16–80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.

The prevalence and mortality rates of severe infections are high in intensive care units (ICUs). At the same time, the high pharmacokinetic variability observed in ICU patients increases the risk of inadequate antibiotic drug exposure. Therefore, dosing tailored to specific patient characteristics has a high potential to improve outcomes in this vulnerable patient population. This study aimed to develop a tabular dosing decision tool for initial therapy of meropenem integrating hospital-specific, thus far unexploited pathogen susceptibility information. An appropriate meropenem pharmacokinetic model was selected from the literature and evaluated using clinical data. Probability of target attainment (PTA) analysis was conducted for clinically interesting dosing regimens. To inform dosing prior to pathogen identification, the local pathogen-independent mean fraction of response (LPIFR) was calculated based on the observed minimum inhibitory concentrations distribution in the hospital. A simple, tabular, model-informed dosing decision tool was developed for initial meropenem therapy. Dosing recommendations achieving PTA > 90% or LPIFR > 90% for patients with different creatinine clearances were integrated. Based on the experiences during the development process, a generalised workflow for the development of tabular dosing decision tools was derived. The proposed workflow can support the development of model-informed dosing tools for initial therapy of various drugs and hospital-specific conditions.