Does osteoporosis reduce the primary tilting stability of cementless acetabular cups?

Background: Cementless hip cups need sufficient primary tilting stability to achieve osseointegration. The aim of the study was to assess differences of the primary implant stability in osteoporotic bone and in bone with normal bone density. To assess the influence of different cup designs, two types of threaded and two types of press-fit cups were tested. Methods: The maximum tilting moment for two different cementless threaded cups and two different cementless press-fit cups was determined in macerated human hip acetabuli with reduced (n=20) and normal bone density (n=20),determined using Q-CT. The tilting moments for each cup were determined five times in the group with reduced bone density and five times in the group with normal bone density, and the respective average values were calculated. Results: The mean maximum extrusion force of the threaded cup Zintra was 5670.5 N (max. tilting moment 141.8 Nm) in bone with normal density and. 5748.3 N (max. tilting moment 143.7 Nm) in osteoporotic bone. For the Hofer Imhof (HI) threaded cup it was 7681.5 N (192.0 Nm) in bone with normal density and 6828.9 N (max. tilting moment 170.7 Nm) in the group with osteoporotic bone. The mean maximum extrusion force of the macro-textured press-fit cup Metallsockel CL was 3824.6 N (max. tilting moment 95.6 Nm) in bone with normal and 2246.2 N (max. tilting moment 56.2 Nm) in osteoporotic bone. For the Monoblock it was 1303.8 N (max. tilting moment 32.6 Nm) in normal and 1317 N (max. tilting moment 32.9 Nm) in osteoporotic bone. There was no significance. A reduction of the maximum tilting moment in osteoporotic bone of the ESKA press-fit cup Metallsockel CL was noticed. Conclusion: Results on macerated bone specimens showed no statistically significant reduction of the maximum tilting moment in specimens with osteoporotic bone density compared to normal bone, neither for threaded nor for the press-fit cups. With the limitation that the results were obtained using macerated bone, we could not detect any restrictions for the clinical indication of the examined cementless cups in osteoporotic bone

Birth Order, Caesarean Section, or Daycare Attendance in Relation to Child- and Adult-Onset Type 1 Diabetes: Results from the German National Cohort

Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

Selbstberichtete Krebserkrankungen in der NAKO Gesundheitsstudie: Erfassungsmethoden und erste Ergebnisse

BACKGROUND: In the German National Cohort (NAKO Gesundheitsstudie), the largest prospective cohort study in Germany, data on self-reported cancer diagnoses are now available for the first half of participants. OBJECTIVES: Description of the methods to assess self-reported cancer diagnoses and type of cancer in the NAKO and presentation of first results. MATERIALS AND METHODS: In a computer-assisted, standardized personal interview, 101,787 participants (54,526 women, 47,261 men) were asked whether they had ever been diagnosed with cancer (malignant tumors including in situ) by a physician and how many cancer diagnoses they had. The type of cancer was classified with a list. Absolute and relative frequencies of self-reported cancer diagnoses and types of cancer were calculated and compared with cancer registry data. RESULTS: A physician-diagnosed cancer was reported by 9.4% of women and 7.0% of men. Of the participants who reported a cancer diagnosis, 88.3% reported to have had only one cancer diagnosis. In women, the most frequent malignancies were breast cancer, cervical cancer, and melanoma. In men, the most frequent malignancies were prostate cancer, melanoma, and colorectal cancer. Comparing the frequencies of cancer diagnoses reported by 45- to 74-year-old NAKO participants within the last five years to cancer registry-based 5‑year prevalences, most types of cancer were less frequent in the NAKO, with the exception of melanoma in men and women, cervical cancer and liver cancer in women, and bladder cancer and breast cancer in men. CONCLUSIONS: The NAKO is a rich data basis for future investigations of incident cancer

Die Basiserhebung der NAKO Gesundheitsstudie: Teilnahme an den Untersuchungsmodulen, Qualitätssicherung und Nutzung von Sekundärdaten

BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20–69 years derived from random samples of the German general population were recruited in 18 study centers (2014–2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.HINTERGRUND: Die NAKO Gesundheitsstudie ist ein bundesweites interdisziplinäres Forschungsvorhaben mit dem Ziel, die Ursachen für chronische Krankheiten und deren vorklinische Stadien zu untersuchen. Der Artikel gibt einen Überblick über das Studiendesign, die Methoden, die Teilnahme an den Untersuchungen und ihre Qualitätssicherung zur Halbzeit der Basiserhebung. METHODEN: Für die Basiserhebung wurden mehr als 200.000 Frauen und Männer im Alter von 20–69 Jahren aus Zufallsstichproben der Allgemeinbevölkerung in 18 Studienzentren rekrutiert (2014–2019). Die Basiserhebung beinhaltet Untersuchungen, Befragungen und Biomaterialien für alle Teilnehmerinnen und Teilnehmer (Level 1), ein erweitertes Programm für mindestens 20 % (Level 2) und eine Magnetresonanztomografie (MRT) für 30.000 Teilnehmerinnen und Teilnehmer. Sekundär- und Registerdaten werden über Krankheitsregister, Kranken- und Rentenversicherungen erhoben. Die Auswertung bezieht die Datenbasis zur Halbzeit der Basiserhebung mit 101.839 Teilnehmerinnen und Teilnehmern ein, davon 11.371 mit einer MRT-Untersuchung. ERGEBNISSE: Die mittlere Responsequote zur Halbzeit betrug insgesamt 18 %. Die Teilnahme an den Untersuchungen lag überwiegend bei mehr als 95 %. Bei 96 % der MRT-Teilnehmerinnen und Teilnehmer konnten alle 12 MRT-Sequenzen vollständig durchgeführt werden. Der Erschließung und wissenschaftlichen Nutzung ergänzender Sekundär- und Registerdaten stimmten mehr als 90 % der Teilnehmerinnen und Teilnehmer zu. DISKUSSION: Die Bereitschaft, möglichst alle Untersuchungsmodule durchzuführen, war trotz des zeitlichen Aufwandes außerordentlich hoch. Dadurch wird die NAKO zu einer zentralen Ressource für die epidemiologische Forschung in Deutschland. Sie wird es ermöglichen, neue Strategien zur Früherkennung, Vorhersage und Primärprävention chronischer Krankheiten zu entwickeln

Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million personyears of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eG FR values 105 mL.min(-1).1.73 m(-2), compared with those with eG FR between 60 and 105 mL.min(-1).1.73 m(-2). Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL.min(-1).1.73 m(-2). Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin Alc, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Dietary patterns as a new approach for understanding the role of nutrition in the etiology of essential arterial hypertension

Die Analyse von Ernährungsmustern hat in jüngster Zeit zunehmendes Interesse gefunden, um Assoziationen zwischen Ernährung und Krankheiten zu untersuchen. Die vorliegende Studie analysierte Assoziationen zwischen Ernährungsmustern und dem Hypertonierisiko bei 3849 Männern und 8552 Frauen, wobei Daten der prospektiven EPIC-Potsdam-Kohortenstudie genutzt wurden. Über eine Nachbeobachtungsperiode von 2-4 Jahren wurden 172 inzidente Hypertoniefälle (49 Männer und 123 Frauen) durch medizinische Verifizierungen bestätigt. Assoziationen der Muster mit dem Erkrankungsrisiko wurden mit Hilfe von Cox-Regressionen getrennt für Männer und Frauen bestimmt, wobei für wichtige Confounder adjustiert wurde. Zwei Muster wurden mittels Hauptkomponentenanalyse in einer Lernstichprobe der gesamten EPIC-Potsdam-Studienpopulation identifiziert und nachfolgend in der Hypertoniestudienpopulation mittels konfirmatorischer Faktoranalyse bestätigt. Das Muster Hausmannskost war positiv mit der Aufnahme von Fleisch, gekochtem Gemüse, Soße, Kartoffeln und Geflügel assoziiert, während das Muster Obst & Gemüse durch Obst, rohes Gemüse und Pflanzenöl gekennzeichnet war. Zusätzlich wurde ein Muster DASH hypothesenorientiert definiert, welches hohe Aufnahmen von Obst, Gemüse und Milchprodukten reflektierte. Das Muster Hausmannskost war negativ mit dem Hypertonierisiko bei Männern aber nicht bei Frauen assoziiert. Die Muster Obst & Gemüse und DASH waren sowohl bei Männern als auch bei Frauen negativ mit der Hypertonieinzidenz assoziiert, wobei nur bei Frauen das Muster DASH statistische Signifikanz nach Kontrolle für potentielle Confounder erlangte. Die Effekte der Muster wurden durch Adjustierung für die Ballaststoff-, Kalium-, Magnesium- und Kalziumaufnahme abgeschwächt. Lebensmittel und Nährstoffe, deren Aufnahme mit den Mustern korrelierte, zeigten vergleichbare Effekte auf die Hypertonieinzidenz im Vergleich zu den Mustern, was die beobachteten Mustereffekte bestätigt. Die vorgelegte Studie unterstützt die Annahme, dass Ernährungsmuster Prädiktoren für Erkrankungsrisiken sind. Insbesondere ein Ernährungsmuster, das durch hohe Aufnahmen von Obst, Gemüse und Milchprodukten gekennzeichnet ist, scheint mit einem verminderten Hypertonierisiko assoziiert zu sein. Der Effekt des Musters ist zum Teil durch die Magnesium-, Ballaststoff-, Kalium- und Kalziumaufnahme erklärbar. Effektmodifikationen durch Übergewicht und körperliche Aktivität wurden zudem beobachtet.The analysis of dietary patterns has recently received growing attention as a possible approach to examine diet-disease associations. This study examined the risk of hypertension associated with dietary patterns in 3849 men and 8552 women based on data from the prospective EPIC-Potsdam cohort study. During the 2-4 years of follow-up, 172 incident hypertension cases (49 men and 123 women) were verified by medical records. Patterns associations with disease risk were estimated by Cox proportional hazard regression stratified by sex and adjusted for potential confounding variables. Two dietary patterns were identified by principal component analysis in a "learning sample" of the total EPIC-Potsdam cohort, and subsequently confirmed by confirmatory factor analysis in the hypertension cohort. The "plain cooking" pattern was positively associated with intakes of meat, cooked vegetables, sauce, potatoes and poultry, whereas the "fruit & vegetables" pattern was associated with intakes of fruit, raw vegetables and vegetable oil. Additionally, a hypothesis-driven pattern "DASH" was defined reflecting high intakes of fruit, vegetables and milk products. The "plain cooking" pattern was inversely associated with hypertension incidence in men, but not women. The patterns "fruit & vegetables" and "DASH" were inversely associated with hypertension incidence in both men and women, however only in women the "DASH" pattern reached statistical significance after controlling for other variables. Pattern effects were attenuated after adjustment for intakes of dietary fibre, potassium, magnesium and calcium. Those food items and nutrients associated with the patterns showed similar effects on hypertension incidence compared to the observed pattern effects, thus confirming the results. The findings partly support the assumption that overall dietary patterns can predict disease risks. Especially a dietary pattern associated with high intakes of fruit, vegetables and milk products seems to be associated with a lower risk of hypertension. The pattern effect can partly be attributed to the intake of magnesium, potassium, dietary fibre and calcium. Additionally, effect modifications by body mass index and physical activity were observed