Impact of P-selectin-PSGL-1 Axis on Platelet-Endothelium-Leukocyte Interactions in Fatal COVID-19.

In critically ill patients infected with SARS-CoV-2, early leukocyte recruitment to the respiratory system was found to be orchestrated by leukocyte trafficking molecules accompanied by massive secretion of proinflammatory cytokines and hypercoagulability. Our study aimed to explore the interplay between leukocyte activation and pulmonary endothelium in different disease stages of fatal COVID-19. Our study comprised 10 COVID-19 postmortem lung specimens and 20 control lung samples (5 acute respiratory distress syndrome, 2 viral pneumonia, 3 bacterial pneumonia, and 10 normal), which were stained for antigens representing the different steps of leukocyte migration: E-selectin, P-selectin, PSGL-1, ICAM1, VCAM1, and CD11b. Image analysis software QuPath was used for quantification of positive leukocytes (PSGL-1 and CD11b) and endothelium (E-selectin, P-selectin, ICAM1, VCAM1). Expression of IL-6 and IL-1ß was quantified by RT-qPCR. Expression of P-selectin and PSGL-1 was strongly increased in the COVID-19 cohort compared with all control groups (COVID-19:Controls, 17:23, P < .0001; COVID-19:Controls, 2:75, P < .0001, respectively). Importantly, P-selectin was found in endothelial cells and associated with aggregates of activated platelets adherent to the endothelial surface in COVID-19 cases. In addition, PSGL-1 staining disclosed positive perivascular leukocyte cuffs, reflecting capillaritis. Moreover, CD11b showed a strongly increased positivity in COVID-19 compared with all controls (COVID-19:Controls, 2:89; P = .0002), indicating a proinflammatory immune microenvironment. Of note, CD11b exhibited distinct staining patterns at different stages of COVID-19 disease. Only in cases with very short disease course, high levels of IL-1ß and IL-6 mRNA were observed in lung tissue. The striking upregulation of PSGL-1 and P-selectin reflects the activation of this receptor-ligand pair in COVID-19, increasing the efficiency of initial leukocyte recruitment, thus promoting tissue damage and immunothrombosis. Our results show that endothelial activation and unbalanced leukocyte migration play a central role in COVID-19 involving the P-selectin-PSGL-1 axis.

Influencing factors of anti-SARS-CoV-2-spike-IgG antibody titers in healthcare workers: A cross-section study.

Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination. anti-SARS-CoV-2-spike IgG titers were determined by SERION ELISA agile SARS-CoV-2 IgG. Mean anti-SARS-CoV-2-spike IgG levels increased significantly by number of COVID-19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID-19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti-SARS-CoV-2-spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS-CoV-2 immunity, adding to the risk of severe infections within this already health impaired collective.

Performance of Three SARS-CoV-2 Immunoassays, Three Rapid Lateral Flow Tests, and a Novel Bead-Based Affinity Surrogate Test for the Detection of SARS-CoV-2 Antibodies in Human Serum.

For the control of immunity in COVID-19 survivors and vaccinated subjects, there is an urgent need for reliable and rapid serological assays. Based on samples from 63 COVID-19 survivors up to 7 months after symptom onset, and on 50 serum samples taken before the beginning of the pandemic, we compared the performances of three commercial immunoassays for the detection of SARS-CoV-2 IgA and IgG antibodies (Euroimmun SARS-COV-2 IgA/IgG, Mikrogen recomWell SARS-CoV-2 IgA/IgG, and Serion ELISA agile SARS-CoV-2 IgA/IgG) and three rapid lateral flow (immunochromatographic) tests (Abbott PanBio COVID-19 IgG/IgM, Nadal COVID-19 IgG/IgM, and Cleartest Corona 2019-nCOV IgG/IgM) with a 50% plaque-reduction neutralization test (PRNT50) representing the gold standard. Fifty-seven out of 63 PCR-confirmed COVID-19 patients (90%) showed neutralizing antibodies. The sensitivity of the seven assays ranged from 7.0% to 98.3%, and the specificity ranged from 86.0% to 100.0%. Only one commercial immunoassay showed a sensitivity and specificity of greater than 98%.

Cefotaxime resistance in invasive Haemophilus influenzae isolates in Germany 2016-19: prevalence, epidemiology and relevance of PBP3 substitutions.

BACKGROUND: Haemophilus influenzae can cause invasive infections, in which cefotaxime is among the first-line antibiotics for treatment. The prevalence of cefotaxime-resistant H. influenzae in Europe is reported to be on a low level. Nevertheless, systematic studies with a large set of invasive isolates are scarce. OBJECTIVES: To provide prevalence data for cefotaxime resistance in invasive H. influenzae isolates in Germany 2016-19 and investigate the epidemiological relevance of PBP3 mutations known to elevate the cefotaxime MIC. METHODS: Cefotaxime susceptibility of invasive H. influenzae isolates, collected in the national laboratory surveillance programme, was examined by gradient agar diffusion (GAD) testing. Cefotaxime resistance was determined according to EUCAST guidelines (resistance breakpoint MIC >0.125 mg/L). Therefore, the MIC for all resistant isolates was verified by broth microdilution method (BMD). WGS was performed to investigate the genetic relationship of cefotaxime-resistant isolates and to analyse alterations in the PBP3. An analysis of the geographic distribution of the resistant isolates was performed. RESULTS: From 2016 to 2019, the German National Reference Laboratory for Meningococci and H. influenzae received 2432 invasive H. influenzae isolates from blood and CSF. According to GAD results, 27 strains were resistant to cefotaxime. BMD confirmed the resistance in 22 of these isolates, which equals a prevalence of cefotaxime resistance of 0.90% in invasive H. influenzae in Germany. Among cefotaxime-resistant isolates cgMLST revealed three clusters. PBP3 analysis showed previously described mutations in our strains. In comparison with cefotaxime-susceptible strains, the alterations L389F and Y557H were significantly associated with cefotaxime resistance, but were not present in all resistant strains. Geographic analysis showed that the disease cases with cefotaxime-resistant H. influenzae were evenly spread throughout the population in Germany. CONCLUSIONS: Cefotaxime is still well suited for the treatment of invasive H. influenzae infections. Rarely occurring cefotaxime resistance is caused by sporadic mutations. The role of PBP3 mutations needs further investigation.

Performance and feasibility of universal PCR admission screening for SARS-CoV-2 in a German tertiary care hospital.

Anamnestic screening of symptoms and contact history is applied to identify coronavirus disease 2019 (COVID-19) patients on admission. However, asymptomatic and presymptomatic patients remain undetected although the viral load may be high. In this retrospective cohort study, all hospitalized patients who received polymerase chain reaction (PCR) admission testing from March 26th until May 24th, 2020 were included. Data on COVID-19-specific symptoms and contact history to COVID-19 cases were retrospectively extracted from patient files and from contact tracing notes. The compliance to the universal testing protocol was high with 90%. Out of 6940 tested patients, 27 new severe acute respiratory syndrome coronavirus-2 infections (0.4%) were detected. Seven of those COVID-19 cases (26% of all new cases) were asymptomatic and had no positive contact history, but were identified through a positive PCR test. The number needed to identify an asymptomatic patient was 425 in the first wave of the epidemic, 1218 in the low incidence phase. The specificity of the method was above 99.9%. Universal PCR testing was highly accepted by staff as demonstrated by high compliance. The costs to detect one asymptomatic case in future studies need to be traded off against the costs and damage caused by potential outbreaks of COVID-19.

Control of a COVID-19 outbreak in a nursing home by general screening and cohort isolation in Germany, March to May 2020.

Elderly care facilities have become a major focus of coronavirus disease (COVID-19) control. Here, we describe an outbreak of COVID-19 in a nursing home in Germany from 8 March to 4 May 2020 (58 days), and the effect of an intervention of general screening and cohort isolation. COVID-19 cases among residents and staff were recorded on a daily basis from the first positive SARS-CoV-2 test from a resident on 8 March 2020, until 4 May 2020 when the last staff member was classified COVID-19 negative. Eighty of 160 residents (50%) and 37 of 135 staff members (27%) tested positive for SARS-CoV-2. Twenty-seven of the 80 residents were asymptomatic but tested positive during the first general screening. Cohort isolation of SARS-CoV-2 positive residents by reorganising the facility proved to be a major effort. After the intervention, four further asymptomatic residents tested positive in follow-up screenings within a period of 6 days, and were possibly infected prior to the intervention. Thereafter, no further infections were recorded among residents. The described outbreak was controlled by implementing general screening and rigorous cohort isolation, providing a blueprint for similar facilities.

Molecular epidemiology of imipenem resistance in invasive Haemophilus influenzae infections in Germany in 2016.

BACKGROUND: The carbapenems imipenem and meropenem play an important role in the empirical anti-infective treatment of critically ill patients. Carbapenem resistance in Haemophilus influenzae (Hi) has rarely been reported. OBJECTIVES: We provide prevalence data for resistance to carbapenems from laboratory surveillance of invasive Hi infections in Germany in 2016. METHODS: Phenotypic susceptibility testing against ampicillin, amoxicillin/clavulanate, cefotaxime and imipenem was carried out on 474 isolates from blood and CSF. The isolates were collected as part of the national laboratory surveillance programme. Imipenem-resistant strains were further tested for meropenem susceptibility. Molecular analysis was done by ftsI sequencing to detect mutations in PBP3, by acrR sequencing to detect alterations in the regulatory protein of the AcrAB-TolC efflux pump and by MLST. RESULTS: No resistance to meropenem was detected. Cefotaxime resistance was rare (n = 3; 0.6%). Imipenem resistance was found in 64 strains (13.5%) using gradient agar diffusion and was confirmed in 26 isolates by broth microdilution (5.5%). Imipenem resistance occurred predominantly in Hi that were ß-lactamase negative but ampicillin resistant and in those that were ß-lactamase positive but nevertheless amoxicillin/clavulanate resistant. This finding suggested a ß-lactamase-independent mechanism. Accordingly, sequence analysis of PBP3 identified previously described mutations. MLST of the imipenem-resistant strains, which were all non-typeable Hi, revealed a high diversity. CONCLUSIONS: We conclude that imipenem, but not meropenem, resistance is frequent in Hi. It is likely to be supported by PBP3 mutations.

Susceptibility of invasive Neisseria meningitidis strains isolated in Germany to azithromycin, an alternative agent for post-exposure prophylaxis.

BACKGROUND: Post-exposure prophylaxis (PEP) for close contacts of invasive meningococcal disease (IMD) cases is recommended in most countries to avoid secondary cases by eradicating supposed meningococcal colonization. Currently, rifampicin, ciprofloxacin and ceftriaxone are recommended in many countries including Germany. Azithromycin has been shown to eradicate meningococcal colonization. OBJECTIVES: To assess the azithromycin susceptibility of invasive Neisseria meningitidis isolates. METHODS: A subset of German invasive meningococcal isolates from 2006-18 was selected for this study. Azithromycin MIC was determined using broth microdilution and agar gradient diffusion. RESULTS: Azithromycin MICs as determined by broth microdilution ranged from <0.003 to 2 mg/L (median 0.50 mg/L, Q75 1 mg/L). All isolates were susceptible to azithromycin according to the CLSI breakpoint (95% CI 0.0%-1.5%). There was no significant correlation between MICs determined by broth microdilution and agar gradient diffusion. Nevertheless, the two methods were consistent regarding the categorization of all isolates as susceptible. CONCLUSIONS: Azithromycin is an eligible antibiotic for PEP of IMD close contacts. It is approved for adults as well as children and may even be used in pregnancy. Because of easier application and lower toxicity, it might be an alternative to rifampicin and ciprofloxacin, as we found no resistant isolates. Since a gonococcal gene associated with elevated azithromycin MICs has been reported in N. meningitidis, careful monitoring of the emergence of resistant strains is nevertheless necessary for meningococci. Lack of concordance of MICs between broth microdilution and agar gradient diffusion needs to be considered.

Failure of first meningococcal vaccination in patients with atypical haemolytic uraemic syndrome treated with eculizumab.

BACKGROUND: The C5 complement inhibitor eculizumab is a first-line treatment in atypical haemolytic uraemic syndrome (aHUS). Therapy with eculizumab is associated with a highly increased risk for meningococcal infection. Therefore, vaccination is highly recommended before beginning treatment. Efficacy of quadrivalent meningococcal vaccines (MenACWY) in patients treated with the C5 complement inhibitor eculizumab in aHUS has not yet been determined. METHODS: Patients with aHUS received one dose of a MenACWY conjugate vaccine before eculizumab treatment commenced. Bactericidal titres against meningococcal serogroups A, C, W and Y were determined using baby rabbit complement in 25 patients. RESULTS: Full immune response to meningococcal vaccination was detected in five patients (20%), while seven patients (28%) showed no immune response in any of the tested serogroups. The remaining 13 patients showed incomplete immune response with proof of protective antibody titres for one to three serogroups without perceptible preference for any serogroup. Bactericidal titres after re-vaccination were available for 17 patients. Nine patients with incomplete immune response after first vaccinations showed protective antibody titres for all serogroups after re-vaccination. Kidney function had improved in >50% of patients at the time of re-vaccination compared with the time of first vaccination and immunosuppressive therapy was only applied to re-vaccinated patients following kidney transplantation. CONCLUSIONS: Immunogenicity of first quadrivalent meninongococcal vaccination is insufficient in patients with aHUS. Booster response is promising, but incomplete. Therefore, establishing antibiotic prophylaxes seems pivotal.

Hospital preparedness for mass critical care during SARS-CoV-2 pandemic.

Mass critical care caused by the severe acute respiratory syndrome corona virus 2 pandemic poses an extreme challenge to hospitals. The primary goal of hospital disaster preparedness and response is to maintain conventional or contingency care for as long as possible. Crisis care must be delayed as long as possible by appropriate measures. Increasing the intensive care unit (ICU) capacities is essential. In order to adjust surge capacity, the reduction of planned, elective patient care is an adequate response. However, this involves numerous problems that must be solved with a sense of proportion. This paper summarises preparedness and response measures recommended to acute care hospitals.

Accuracy of diagnostic classification and clinical utility assessment of ICD-11 compared to ICD-10 in 10 mental disorders: findings from a web-based field study.

In this web-based field study, we compared the diagnostic accuracy and clinical utility of 10 selected mental disorders between the ICD-11 Clinical Descriptions and Diagnostic Guidelines (CDDG) and the ICD-10 CDDG using vignettes in a sample of 928 health professionals from all WHO regions. On average, the ICD-11 CDDG displayed significantly higher diagnostic accuracy (71.9% for ICD-11, 53.2% for ICD-10), higher ease of use, better goodness of fit, higher clarity, and lower time required for diagnosis compared to the ICD-10 CDDG. The advantages of the ICD-11 CDDG were largely limited to new diagnoses in ICD-11. After limiting analyses to diagnoses existing in ICD-11 and ICD-10, the ICD-11 CDDG were only superior in ease of use. The ICD-11 CDDG were not inferior in diagnostic accuracy or clinical utility compared to the ICD-10 CDDG for any of the vignettes. Diagnostic accuracy was consistent across WHO regions and independent of participants' clinical experience. There were no differences between medical doctors and psychologists in diagnostic accuracy, but members of other health professions had greater difficulties in determining correct diagnoses based on the ICD-11 CDDG. In sum, there were no differences in diagnostic accuracy for diagnoses existing in ICD-10 and ICD-11, but the introduction of new diagnoses in ICD-11 has improved the diagnostic classification of some clinical presentations. The favourable clinical utility ratings of the ICD-11 CDDG give reason to expect a positive evaluation by health professionals in the implementation phase of ICD-11. Yet, training in ICD-11 is needed to further enhance the diagnostic accuracy.

Recurrent invasive meningococcal infections - quantifying the risk, Germany, 2002 to 2018.

IntroductionInvasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection.AimThe German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection.MethodsRecurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD.ResultsAmong 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p < 0.0001).DiscussionPatients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.

Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017.

BackgroundThe total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries.AimThe aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe.MethodsIn this observational, retrospective study, IMD surveillance data collected from 2013-17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics.ResultsThe overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11.ConclusionDuring the years 2013-17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.

[Development of an electronic death certificate for Germany]. / Entwicklung einer elektronischen Todesbescheinigung für Deutschland.

The certification of causes of death by physicians as well as further processing by local health offices, registrar's offices, statistical offices, and other public authorities are conducted in a paper-based way and regulated individually by the laws of the different states of Germany.The concept of a nationally standardized electronic death certificate (eTB), enabling a digitalized processing chain and timely and improved mortality statistic, is presented.Starting with a nationally agreed upon data set, aligned with WHO requirements, an electronic death certificate pilot will be developed and tested in different regions. Synergies resulting from digitalization of the public administration and of the health system will be harnessed.Data collected electronically in the testing phase will be processed with the electronic coding system Iris. Effects on data quality of national mortality statistics will be investigated through multicausal analysis, which will be compared to results from other countries, and through comparisons with data from the existing paper-based process. For the first time, a national multicausal analysis of causes of death will be conceptualized in order to visualize effects of the aging and multimorbid population in national mortality statistics for consideration by healthcare politics and research.Results and lessons learned from the pilot can serve as the basis for national implementation of an electronic death certificate in Germany.

Use of Gene Expression Analysis for Discrimination of Primary and Secondary Adenocarcinoma of the Liver.

BACKGROUND: Due to late diagnosis and resistance to chemotherapy, most patients with cholangiocarcinoma have an unfavorable prognosis. Despite the use of immunohistochemistry (IHC) in clinical routine, differentiation between intrahepatic cholangiocarcinoma (ICC) and secondary adenocarcinomas of the liver is frequently not clear, leading to false diagnosis and treatment decisions. METHODS: Oligonucleotide microarrays (Affymetrix Hu133A©) were used for gene expression analysis of ICC (n = 11) and secondary adenocarcinomas (colorectal metastases; n = 6). By two-dimensional cluster analysis a specific gene expression profile of these tumors was established and confirmed by real-time polymerase chain reaction and IHC. RESULTS: A total of 338 genes were significantly dysregulated (gene expression/fc ≥2; dysregulation in ≥60%) in both tumor groups. Using two-dimensional cluster analysis a fast, clear, and reproducible differentiation between ICC and colorectal metastases was possible in all cases. As potential biomarkers for differentiation, twelve genes (ICC: KRT7, DBN1, LCTB, LIF, STK17A, PIGF; metastases: TDGF1, HOXA9, TFF3, MYB, ABP1, BCL11A) were detected and will be used for further investigations. CONCLUSIONS: A specific gene expression profile for discrimination of primary and secondary adenocarcinoma of the liver could be established. In addition, marker genes for both cancers and their potential use as discrimination markers in clinical routine were also described partially for the first time.

Wild-type isolates of Porphyromonas gingivalis derived from periodontitis patients display major variability in platelet activation.

In vitro studies revealed that Porphyromonas gingivalis (Pg), a pathogen intimately associated with the onset and progression of periodontitis, is able to activate platelets, thus linking periodontal inflammation with the endangerment of vascular health. As wild-type Pg strains are characterized by major genetic heterogeneity, the commonness of platelet-activating Pg strains in periodontitis patients is unknown as of yet. Therefore, this study evaluated the platelet activation capacity of wild-type Pg isolates sampled from patients with aggressive periodontitis. METHODS: Extent and velocity of platelet aggregation were determined by light transmission aggregometry. Platelet surface expression of P-selectin was measured by flow cytometry, activation of p38 MAP kinase, and protein kinase C by Western blot using phospho-specific antibodies. RESULTS: Pg isolates displayed high variability regarding extent and velocity of platelet activation, as well as the involved activating pathways. Corresponding results were observed for platelet P-selectin expression, activation of p38 MAP kinase, or protein kinase C. Inhibitors of platelet immune receptor FcγRIIA and protease-activated receptors revealed several, diverging pathways of activation. Some isolates induced platelet aggregation even in the presence of potent therapeutical platelet inhibitors. CONCLUSIONS: Chronic bacteremia involving specific, platelet-activating Pg strains may constitute a substantial hazard for the integrity of cardiovascular health.

Impact of different concentrations of an octenidine dihydrochloride mouthwash on salivary bacterial counts: a randomized, placebo-controlled cross-over trial.

OBJECTIVES: This bi-centric, placebo-controlled, randomized, evaluator-blinded, incomplete cross-over clinical phase II trial was initialized to identify the most appropriate concentration of octenidine dihydrochloride (OCT) in mouth rinses. MATERIALS AND METHODS: Rinses of 0.10, 0.15, and 0.20% OCT were compared to a saline placebo rinse regarding the reduction of salivary bacterial counts (SBCs) in 90 gingivitis patients over 4 days. Changes in plaque (PI) and gingival index (GI), taste perception, and safety issues were evaluated. RESULTS: At baseline, the first OCT (0.10, 0.15, 0.20%) rinse resulted in a decrease of SBC (reduction by 3.63-5.44 log10 colony forming units [CFU]) compared to placebo (p < 0.001). Differences between OCT concentrations were not verified. After 4 days, the last OCT rinse again resulted in a significant SBC decrease (3.69-4.22 log10 CFU) compared to placebo (p < 0.001). Overall, SBC reduction between baseline and day 4 was significantly higher in OCT 0.15 and 0.20% groups compared to OCT 0.10% and placebo. Mean GI/PIs were significantly lower in OCT groups than in the placebo group (p < 0.001). Differences in GI/PI between OCT groups were not verified. Adverse effects increased with increasing OCT concentrations. CONCLUSIONS: Considering antibacterial efficacy, frequency of adverse events, and user acceptance, 0.10% OCT was identified as the preferred concentration to be used in future clinical trials. CLINICAL RELEVANCE: Due to its low toxicity and pronounced antibacterial properties, octenidine dihydrochloride (OCT) is a promising candidate for the use in antiseptic mouth rinses. OCT concentrations of 0.10% are recommended for future clinical trials evaluating the plaque-reducing properties of OCT mouth rinses. ( www.clinicaltrials.gov , NCT022138552).

[Cause-of-death statistics and ICD, quo vadis?] / Todesursachenstatistik und ICD, quo vadis?

The International Statistical Classification of Diseases and Related Health Problems (ICD) is the worldwide binding standard for generating underlying cause-of-death statistics. OBJECTIVES: What are the effects of former revisions of the ICD on underlying cause-of-death statistics and which opportunities and challenges are becoming apparent in a possible transition process from ICD-10 to ICD-11?This article presents the calculation of the exploitation grade of ICD-9 and ICD-10 in the German cause-of-death statistics and quality of documentation. Approximately 67,000 anonymized German death certificates are processed by Iris/MUSE and official German cause-of-death statistics are analyzed.In addition to substantial changes in the exploitation grade in the transition from ICD-9 to ICD-10, regional effects become visible. The rate of so-called "ill-defined" conditions exceeds 10%.Despite substantial improvement of ICD revisions there are long-known deficits in the coroner's inquest, filling death certificates and quality of coding. To make better use of the ICD as a methodological framework for mortality statistics and health reporting in Germany, the following measures are necessary: 1. General use of Iris/MUSE, 2. Establishing multiple underlying cause-of-death statistics, 3. Introduction of an electronic death certificate, 4. Improvement of the medical assessment of cause of death.Within short time the WHO will release the 11th revision of the ICD that will provide additional opportunities for the development of underlying cause-of-death statistics and their use in science, public health and politics. A coordinated effort including participants in the process and users is necessary to meet the related challenges.

[Field tests for the beta version of the ICD-11-MMS in Germany: background and methods]. / Feldtests zur Betaversion der ICD-11-MMS in Deutschland: Hintergrund und Methodik.

BACKGROUND: The World Health Organization (WHO) has been developing the 11th revision of the International Classification of Diseases (ICD) since 2007. ICD-11 is different from the ICD-10 in volume and structure. Therefore, the WHO planned field tests with a coding of diagnoses and cases. OBJECTIVES: To describe the background of the field tests and their implementation in Germany. MATERIALS AND METHODS: Interested parties were invited to submit proposals through a call to the Association of the Scientific Medical Societies (AWMF). The Technology, Methods, and Infrastructure for Networked Medical Research (TMF) was responsible for the coordination, supported by the German Institute for Medical Documentation and Information (DIMDI). The target was a beta version of the ICD-11 for Mortality and Morbidity Statistics (ICD-11-MMS), denoted as "draft for quality assurance". RESULTS: Eleven field tests were maintained between March and September 2017. With the exception of one field test analyzing diagnoses terms from the thesaurus of the ICD-10-GM, all field tests focused on a specific medical field. Eight different quality criteria were investigated over the 11 field tests, and 22 of the 27 chapters of the ICD-11-MMS were at least partially covered. CONCLUSIONS: Despite the strict time frame, the field tests were successfully implemented and concluded in Germany. Mostly, the ICD-11 tools from the WHO were used. A high percentage of the ICD chapters were partially covered. In summary, it has been demonstrated for the first time that field tests are a valuable approach to evaluate the ICD in parallel to its development. However, a methodological framework integrating the field tests should be developed, taking into account all relevant requirements.