Grip strength values and cut-off points based on over 200,000 adults of the German National Cohort - a comparison to the EWGSOP2 cut-off points

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP) updated in 2018 the cut-off points for low grip strength to assess sarcopenia based on pooled data from 12 British studies. OBJECTIVE: Comparison of the EWGSOP2 cut-off points for low grip strength to those derived from a large German sample. METHODS: We assessed the grip strength distribution across age and derived low grip strength cut-off points for men and women (peak mean -2.5 × SD) based on 200,389 German National Cohort (NAKO) participants aged 19-75 years. In 1,012 Cooperative Health Research in the Region of Augsburg (KORA)-Age participants aged 65-93 years, we calculated the age-standardised prevalence of low grip strength and time-dependent sensitivity and specificity for all-cause mortality. RESULTS: Grip strength increased in the third and fourth decade of life and declined afterwards. Calculated cut-off points for low grip strength were 29 kg for men and 18 kg for women. In KORA-Age, the age-standardised prevalence of low grip strength was 1.5× higher for NAKO-derived (17.7%) compared to EWGSOP2 (11.7%) cut-off points. NAKO-derived cut-off points yielded a higher sensitivity and lower specificity for all-cause mortality. CONCLUSIONS: Cut-off points for low grip strength from German population-based data were 2 kg higher than the EWGSOP2 cut-off points. Higher cut-off points increase the sensitivity, thereby suggesting an intervention for more patients at risk, while other individuals might receive additional diagnostics/treatment without the urgent need. Research on the effectiveness of intervention in patients with low grip strength defined by different cut-off points is needed

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

Design und Qualitätskontrolle der zahnmedizinischen Untersuchung in der NAKO Gesundheitsstudie [Design and quality control of the oral health status examination in the German National Cohort (GNC)]

BACKGROUND: Caries and periodontitis are highly prevalent worldwide. Because detailed data on these oral diseases were collected within the framework of the German National Cohort (GNC), associations between oral and systemic diseases and conditions can be investigated. OBJECTIVES: The study protocol for the oral examination was designed to ensure a comprehensive collection of dental findings by trained non-dental staff within a limited examination time. At the mid-term of the GNC baseline examination, a first quality evaluation was performed to check the plausibility of results and to propose measures to improve the data quality. MATERIALS AND METHODS: A dental interview, saliva sampling and oral diagnostics were conducted. As part of the level‑1 examination, the number of teeth and prostheses were recorded. As part of the level‑2 examination, detailed periodontal, cariological and functional aspects were examined. All examinations were conducted by trained non-dental personnel. Parameters were checked for plausibility and variable distributions were descriptively analysed. RESULTS: Analyses included data of 57,967 interview participants, 56,913 level‑1 participants and 6295 level‑2 participants. Percentages of missing values for individual clinical parameters assessed in level 1 and level 2 ranged between 0.02 and 3.9%. Results showed a plausible distribution of the data; rarely, implausible values were observed, e.g. for measurements of horizontal and vertical overbite (overjet and overbite). Intra-class correlation coefficients indicated differences in individual parameters between regional clusters, study centres and across different examiners. CONCLUSIONS: he results confirm the feasibility of the study protocol by non-dental personnel and its successful integration into the GNC's overall assessment program. However, rigorous dental support of the study centres is required for quality management

Feasibility and acceptance of cervicovaginal self-sampling within the German National Cohort (Pretest 2)

Hintergrund und Ziele: In der Nationalen Kohorte (NAKO) werden 100.000 erwachsene Frauen in Deutschland umfassend befragt und untersucht werden. Während Frauengesundheit im Basisinterview thematisiert wird, ist der direkte Erregernachweis von cervicovaginalen mikrobiellen Besiedlungen oder Infektionen nicht Teil des Untersuchungsprotokolls. In einem Pilotprojekt untersuchten wir daher die Machbarkeit der häuslichen Selbstentnahme einer cervicovaginalen Lavage durch Studienteilnehmerinnen der NAKO ohne Kontakt zu einem Frauenarzt oder anderem medizinischen Personal. Wir explorierten außerdem die Möglichkeit bei diesem Vorgehen, verschiedene vaginal auftretende Erreger und Erkrankungen, inklusive humane Papillomviren (HPV), Chlamydia trachomatis und bakterielle Vaginose (BV) nachzuweisen. Methoden: Wir führten die Studie als Querschnittsstudie 2012 während Pretest 2 als zusätzliches Modul zum Hauptprogramm der NAKO in zwei Studienzentren (Hamburg und Hannover) durch. Die Teilnehmerinnen entstammen einer zufällig gezogenen Einwohnermeldeamtstichprobe. Sie führten nach Aufklärung und schriftlicher Einverständniserklärung im Studienzentrum auf Basis einer schriftlichen Anweisung die Probenentnahme zuhause durch (Delphi ScreenerTM). Die Proben und Akzeptanzfragebögen wurden per Post von den Teilnehmerinnen direkt an das Labor bzw. an das jeweilige Studienzentrum gesandt. Akzeptanz wurde in drei Kategorien abgefragt: Zustimmung, teilweise Zustimmung, Ablehnung. Die Proben wurden per Multiplex-Papillomvirusgenotypisierung auf Anwesenheit von 27 mukosalen HPV-Typen untersucht. Der Nachweis anderer Pathogene erfolgte durch „Sexually Transmitted Infection Profiling“ (STIP), einer neuen Multiplex- Polymerase-Kettenreaktion (PCR) für verschiedene vaginal auftretende Erreger/Erkrankungen mit anschließender „Bead“-basierter Luminex®-Hybridisierung. Als Positivkontrolle wurden ß-Globin (HPV-Nachweis) und die humane DNA Polymerase alpha (PolA)-Sequenz (STIP) nachgewiesen. Ergebnisse: Die Teilnahme als Anteil an allen Frauen in Pretest 2, die an Zusatzmodulen in den betreffenden Studienzentren teilnehmen konnten, lag bei 67,3 % (109/162). Die Altersspanne der Probandinnen reichte von 20 bis 69 Jahre. Im Median dauerte die Probenentnahme nach Angaben der Probandinnen 5 Minuten. Die Analyse der Akzeptanzfragebögen (n = 108) ergab, dass die selbstständige Durchführung einer cervicovaginalen Lavage für 98 % der Frauen akzeptabel war (106/108), dass 89 % die Probenentnahme als leicht (96/108) und 96 % als benutzerfreundlich einstuften (104/108). Beta-Globin und PolA als Marker für humane DNA und Probenqualität konnte bei allen untersuchten Proben nachgewiesen werden, während HPV als Marker für Pathogenerfassbarkeit in 18 von 109 Proben nachgewiesen wurde. Von 107 mittels STIP als zweitem Marker für Pathogenerfassbarkeit untersuchten Proben wurden 5 von den statistischen Analysen bakterieller Erreger aufgrund von Hinweisen in den Laboranalysen auf Antibiotikaeinnahme ausgeschlossen. Um zu berechnen, ob bakterielle Vaginose oder Candidose vorhanden sind, wurden 7 bzw. 8 Proben aufgrund niedriger Signalintensitäten ausgeschlossen. Dies führte zur Evaluierung von 95 bzw. 94 Proben. Wir konnten z.B. Ureaplasma parvum in 22 von 102 Proben nachweisen, bakterielle Vaginose in 14 von 95 Proben und Candidose in 13 von 94 Proben. Chlamydia trachomatis konnte in keiner Probe detektiert werden. Schlussfolgerung: Unsere Machbarkeitsstudie zur cervicovaginalen Probenselbstentnahme zeigt, dass diese Bioprobengewinnung im Kontext der NAKO sehr gut akzeptiert wurde und hinsichtlich Pathogennachweisen machbar ist. Die zukünftige Anwendung in der Nationalen Kohorte würde es ermöglichen, Transienz/Persistenz oder langfristige Effekte vaginaler (Ko-) Infektionen und Kolonisationen zu untersuchen.Background and objectives: Within the German National Cohort (GNC) 100,000 adult women in Germany will be comprehensively interviewed and examined. While women’s health is addressed in the basic interview, direct detection of cervicovaginal microbial colonisation or infection is not part of the examination protocol. In a pilot project the feasibility of female study participants of the GNC collecting a cervicovaginal lavage at home without having to involve a gynecologist or other medical personnel was thus investigated. The ability of the procedure to detect vaginal microbes and conditions including human papillomavirus (HPV), Chlamydia trachomatis and bacterial vaginosis (BV) were also explored. Methods: This cross-sectional study was conducted in two study centers (Hamburg and Hanover) of the GNC during Pretest 2 in 2012 as an add-on module to the main program of the National Cohort. Participants were randomly selected through the population registration office. After providing written informed consent at the study center, participants self-collected a cervicovaginal lavage (Delphi Screener™) at home following written instructions. Participants mailed samples and acceptability questionnaires to the laboratory and the study center, respectively. Acceptability of self-sampling was categorized as consent, partial consent and rejection. The samples were analyzed by multiplex HPV genotyping for the presence of 27 mucosal HPV subtypes. To detect other pathogens “Sexually Transmitted Infection Profiling” (STIP) was used, a novel multiplex polymerase chain reaction (PCR) for various vaginally occurring pathogens/conditions coupled with subsequent bead-based Luminex® hybridization. Human beta-globin and DNA polymerase alpha (PolA) sequences were used as positive controls for the detection of human DNA during HPV detection and STIP, respectively. Results: The participation based on the proportion of all women in Pretest 2 who could take part in the add-on Pretest 2 was 67.3 % (109 out of 162). The age of participants ranged from 20 to 69 years. The self-reported median duration of the collection of the lavage was 5 min. Analysis of the questionnaires (n = 108) revealed that the self-sampling of a cervicovaginal lavage was acceptable to 98 % of women (106 out of 108), and considered to be easy by 89 % (96 out of 108) as well as user-friendly by 96 % of the women (104 out of 108). Human beta-globin and PolA as markers for human DNA and sample quality were detected in all samples analyzed while HPV as a marker for pathogen detectability was identified in 18 out of 109 samples. Of the 107 samples tested with STIP as a second marker for pathogen detectability, 5 samples were excluded from statistical analyses on bacterial colonization because of signs in the laboratory results of the use of antibiotics. For the computation of the possible occurrence of bacterial vaginosis and candidiasis 7 and 8 samples, respectively, were excluded because of low signal intensities resulting in an evaluation of 95 or 94 samples, respectively. Ureaplasma parvum was detected in 22 out of 102 samples, BV in 14 out of 95 samples and candidiasis in 13 out of 94 samples. Chlamydia trachomatis was not detected in any sample. Conclusion: The feasibility study on cervicovaginal self-sampling indicates that this form of biosampling was very well accepted within the framework of the GNC and feasible in terms of pathogen detection. Its further application in the GNC would allow investigation of transience and persistence, or long-term effects of vaginal (co)infections and colonization

Comparison of stool collection on site versus at home in a population-based study: Feasibility and participants’ preference in Pretest 2 of the German National Cohort

BACKGROUND: For certain laboratory investigations it is necessary to obtain native stool samples and process them within a narrow time window at the point of contact or a nearby laboratory. However, it is not known whether it is feasible to obtain stool samples from asymptomatic individuals during an appointment in a study center (SC). We therefore compared participants’ preference, feasibility and acceptance of stool sample collection during the appointment at the study center (on-site sampling) to collection at home after the appointment. METHODS: The study was conducted at two sites in Northern Germany (Bremen, n = 156; Hannover, n = 147) during the Pretest 2 phase of the German National Cohort (GNC), drawing upon a randomly selected population supplemented by a small convenience sample. In the study center, the participants were given the choice to provide a stool sample during the appointment or to collect a sample later at home and return it by mail. RESULTS: In all, 303 of the 351 participants (86 %) of Pretest 2 at these sites participated in this feasibility study. Only 7.9 % (24/303) of the participants chose on-site collection, whereas 92 % (279/303) chose at-home collection. There were significant differences between the two study sites in that 14% (21/147) of participants in Hannover and 2% (3/156) of participants in Bremen chose on-site collection. Compliance was high in both groups, as 100 % (24/24) and 98 % (272/279) of participants in the on-site and at-home groups, respectively, provided complete samples. Both methods were highly accepted, as 92 % of the participants in each group (22/24 and 227/248) stated that stool collection at the respective site was acceptable. CONCLUSION: When given a choice, most participants in this population-based study preferred home collection of stool samples to collection in the study center. Thus, native stool samples for immediate processing in the study center may potentially be obtained only from a subpopulation of participants, which may lead to selection bias. Home collection, on the other hand, proved to be a highly feasible method for studies that do not require freshly collected native stool.HINTERGRUND: Für die Durchführung bestimmter Laboranalysen wird Nativstuhl benötigt, der zeitnah vor Ort oder in einem nahegelegenen Labor verarbeitet werden muss. Bislang ist nicht bekannt, ob es möglich ist, Stuhlproben von gesunden Probanden während ihres Aufenthaltes im Studienzentrum zu erhalten. Wir haben daher die Präferenz von Studienteilnehmern sowie die Machbarkeit und Akzeptanz der Stuhlprobengewinnung während des Termins im Studienzentrum im Vergleich zur Stuhlprobengewinnung zu Hause nach dem Termin im Studienzentrum untersucht. METHODEN: Die Studie wurde während des Pretest 2 der Nationalen Kohorte in 2 Studienzentren Norddeutschlands (Bremen, n = 156; Hannover, n = 147), basierend auf einer Zufallsstichprobe und ergänzt durch ein kleines Convenience Sample, durchgeführt. Im Studienzentrum wurden die Probanden vor die Wahl gestellt, entweder die Stuhlproben während des Termins im Studienzentrum abzugeben oder später zu Hause und die Stuhlproben per Post zurückzusenden. ERGEBNISSE: Für eine Teilnahme an der Machbarkeitsstudie haben sich 303 von 351 (86 %) der Pretest-2-Probanden beider Studienzentren entschieden. Nur 7,9 % (24/303) der Probanden entschieden sich für die Gewinnung der Stuhlprobe im Studienzentrum, während 92 % (279/303) die Heimgewinnung vorzogen. Es gab signifikante Unterschiede zwischen den beteiligten Studienzentren insofern, als 14 % (21/147) der Probanden in Hannover und 2 % (3/156) der Probanden in Bremen die Stuhlgewinnung im Studienzentrum gewählt haben. Die Compliance war in beiden Gruppen hoch: 100 % (24/24) der Probanden mit Stuhlsammlung im Studienzentrum und 98 % (272/279) der Probanden mit Stuhlsammlung zu Hause haben vollständige Stuhlproben abgegeben. Es gab eine hohe Akzeptanz für beide Methoden: Jeweils 92 % der Probanden beider Gruppen (22/24 und 227/248) bewerteten die Gewinnung im Studienzentrum bzw. zu Hause als akzeptabel. DISKUSSION: Vor die Wahl gestellt, haben sich die meisten Probanden in dieser bevölkerungsbasierten Studie für die Gewinnung von Stuhlproben zu Hause statt im Studienzentrum entschieden. Daher können Nativstuhlproben wohl nur von einer kleinen Gruppe von Probanden für die sofortige Verarbeitung im Studienzentrum gewonnen werden, was möglicherweise zu Selektionsverzerrungen führt. Andererseits hat sich die Heimgewinnung als sehr zuverlässige Methode für Fragestellungen, die keine frisch gewonnenen Nativstuhlproben erfordern, erwiesen