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Aims/hypothesis To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death. Methods This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach. Results A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA1c (53–75 mmol/mol [7–9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m2 increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×109/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19 vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out. Conclusions/interpretation Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease. Registration PROSPERO registration no. CRD42020193692. Previous version This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 Funding The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD). Graphical Abstract

Aims Hemoglobin A1c (HbA1c) has been repeatedly questioned as a valid surrogate marker, especially for patient-relevant outcomes. The aim of this study was to validate the HbA1c value as a surrogate for all-cause mortality in people with type 2 diabetes. Methods The effect estimates for HbA1c lowering after treatment as well as reductions in all-cause mortality of randomized trials were extracted from a systematic review and updated. For the measurement of actual surrogacy, weighted linear regression models with a random intercept for the study effect were used with the all-cause mortality estimate (risk difference and log relative risk) as the outcome and the estimate for HbA1c difference as the covariate. Surrogacy was assessed according to the criteria of Daniels and Hughes. Results A total of 346 HbA1c-mortality-pairs from 205 single randomized trials were included in the analysis. Regarding the risk difference of all-cause mortality, there was no evidence for surrogacy of the HbA1c value. For the log relative risk, a small positive association between HbA1c and the all-cause mortality estimate (slope 0.129 [95% confidence interval −0.043; 0.302]) was observed. However, there was no sign of valid surrogacy. Conclusions Based on the results of more than 200 randomized trials, HbA1c is not a valid surrogate marker for all-cause mortality in people with type 2 diabetes.

Purpose The aim of this study was to examine the mediation of body mass index (BMI) on the association between per capita sugar consumption and diabetes prevalence using country-related data. Research design and methods In this ecological study, based on 192 countries, data on per capita sugar consumption were obtained from the Food and Agriculture Organization of the United Nations (FAO), on BMI from the World Health Organization and on diabetes prevalence from the International Diabetes Federation. Data on demography and economic factors were obtained from the Central Intelligence Agency, the United Nations and the FAO. Multiple linear regression analysis was performed to investigate the association between per capita sugar consumption and diabetes prevalence, and mediation analysis to detect the mediated percentage of BMI on this association. Results Each increase of 100 kcal/day per capita sugar consumption was associated with a 1.62% higher diabetes prevalence [adjusted β-estimator (95% CI): 1.62 (0.71, 2.53)]. Mediation analysis using BMI as the mediator demonstrated an adjusted direct association of 0.55 (95% CI: − 0.22, 1.32) and an adjusted indirect association of 1.07 (95% CI: 0.54, 1.68). Accordingly, the BMI explained 66% (95% CI: 34%, 100%) of the association between per capita sugar consumption on diabetes prevalence. Conclusions These findings indicate that the association between dietary sugar intake and the occurrence of diabetes is mediated by BMI to a large proportion. However, it seems that other mechanisms may explain the association between sugar consumption and development of type 2 diabetes.

HINTERGRUND: In der NAKO Gesundheitsstudie liegen die Daten zu selbstberichteten Krebserkrankungen der ersten Hälfte der Teilnehmenden vor. ZIEL: Beschreibung der Methoden zur Erfassung selbstberichteter Krebserkrankungen und Tumorlokalisationen in der NAKO und Darstellung erster Ergebnisse. MATERIAL UND METHODEN: In einem computergestützten, standardisierten persönlichen Interview wurden 101.787 Teilnehmende (54.526 Frauen, 47.261 Männer) gefragt, ob bei ihnen jemals eine Krebserkrankung (bösartiger Tumor einschließlich in situ) ärztlich diagnostiziert wurde und wie viele Krebserkrankungen sie hatten. Anhand einer Liste wurde die Tumorlokalisation erfragt. Absolute und relative Häufigkeiten von Selbstangaben zu Krebserkrankungen insgesamt und einzelnen Tumorlokalisationen wurden berechnet und mit krebsregisterbasierten Daten verglichen. ERGEBNISSE: Eine ärztlich diagnostizierte Krebserkrankung wurde von 9,4 % der Frauen und 7,0 % der Männer berichtet. Von den Personen, die eine Krebserkrankung berichteten, gaben 88,3 % der Teilnehmenden an, nur eine Krebserkrankung gehabt zu haben. Bei Frauen war die häufigste bösartige Krebserkrankung Brustkrebs, gefolgt von Gebärmutterhalskrebs und malignem Melanom, bei Männern Prostatakrebs, gefolgt von malignem Melanom und Darmkrebs. Beim Vergleich der Krebserkrankungen, die von 45- bis 74-jährigen NAKO-Teilnehmenden in den letzten fünf Jahren berichtet wurden, mit krebsregisterbasierten 5‑Jahres-Prävalenzen wurden für die meisten Tumorlokalisationen in der NAKO niedrigere relative Häufigkeiten beobachtet. Vergleichsweise häufiger traten das maligne Melanom sowie Gebärmutterhalskrebs und Leberkrebs bei Frauen und Harnblasenkrebs und Brustkrebs bei Männern auf. DISKUSSION: Die NAKO ist eine reichhaltige Datenbasis für die zukünftige Untersuchung inzidenter Krebserkrankungen. 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. MATERIAL 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 korperliche Aktivitat stellt ein komplexes Verhalten dar, dessen valide und reliable Erfassung in gros angelegten populationsbasierten Studien mit besonderen Herausforderungen einhergeht. In der bundesweiten NAKO Gesundheitsstudie liegen zur Halbzeit der Basiserhebung die Daten zur korperlichen Aktivitat fur 100.000 Teilnehmende vor. Beschreibung der Erfassung der korperlichen Aktivitat und Prasentation erster deskriptiver Ergebnisse. Das multimodale Erhebungskonzept bestand aus zwei Fragebogen, dem Questionnaire on Annual Physical Activity Pattern (QUAP) und dem Global Physical Activity Questionnaire (GPAQ), einem computerbasierten Erinnerungsprotokoll der vergangenen 24 h (cpar24) und einer 7‑Tage-Akzelerometrie (Actigraph GT3X/+; Fa. ActiGraph, Pensacola, FL, USA). Fur die einzelnen Erhebungsmodule lagen auswertbare Datensatze in unterschiedlicher Zahl vor (QUAP: n = 16.372; GPAQ: n = 90.900; cpar24: n = 23.989; Akzelerometrie: n = 35.218). Die Analysen der einzelnen Module ergaben unterschiedliche Durchschnittswerte fur die moderate oder intensive korperliche Gesamtaktivitat der Teilnehmenden: Bei Frauen wurden 75–216 min/Tag gemessen, bei Mannern 73–224 min/Tag. Personen der Altersgruppe 20–39 Jahre verbrachten 66–200 min/Tag in moderater oder intensiver korperlicher Gesamtaktivitat, wahrend Personen der Altersgruppe 40–69 Jahre 78–244 min/Tag aufwendeten. Erste modulubergreifende Analysen der korperlichen Aktivitat in der NAKO zeigen den Nutzen komplementar eingesetzter Erhebungsmethoden. Die umfangreichen Daten stellen eine wertvolle Ressource fur die Charakterisierung der Zusammenhange zwischen korperlicher Aktivitat und Krankheitspravention dar, die in der Zukunft erfolgen soll.

HINTERGRUND: Personen mit Migrationshintergrund (PmM) unterscheiden sich als Bevölkerungsgruppe hinsichtlich Morbidität, Mortalität und Inanspruchnahme des Gesundheitssystems meist von der autochthonen Bevölkerung, sie nehmen jedoch seltener an Gesundheitsstudien teil. Die Gruppe der PmM ist sehr heterogen, was in Studien bisher kaum berücksichtigt wird. ZIEL DER ARBEIT: Es werden soziodemografische Charakteristika der PmM in der NAKO Gesundheitsstudie (Alter, Geschlecht, Zeit seit Migration, Bildung) dargestellt. Zudem wird exemplarisch untersucht, ob der Migrationshintergrund mit der Nutzung des Angebots zur Früherkennung von Darmkrebs (Hämoccult-Test) zusammenhängt. METHODEN: Daten der ersten 101.816 Teilnehmenden der NAKO wurden deskriptiv und kartografisch ausgewertet. Die Zuweisung des Migrationshintergrunds erfolgte anhand der Definition des Statistischen Bundesamts und basiert auf Staatsangehörigkeit, Geburtsland, Einreisejahr und Geburtsland der Eltern. ERGEBNISSE: Der Anteil der PmM liegt bei 16,0 %. Die Verteilung über die 18 Studienzentren variiert zwischen 6 % (Neubrandenburg) und 33 % (Düsseldorf). Mit 153 Herkunftsländern sind in der NAKO die meisten Länder vertreten. Bei allen Variablen zeigen sich deutliche Unterschiede zwischen den verschiedenen Herkunftsregionen. Am Hämoccult-Test nehmen türkeistämmige Personen (OR = 0,67) und Aussiedler aus der ehemaligen Sowjetunion (OR = 0,60) seltener teil. PmM, die in Deutschland geboren sind, unterscheiden sich diesbezüglich nicht von der autochthonen Bevölkerung (OR = 0,99). DISKUSSION: PmM in der NAKO sind eine sehr heterogene Gruppe. Jedoch lassen sich aufgrund der Stichprobengröße einzelne Untergruppen der PmM hinsichtlich ihrer Herkunftsregion separat untersuchen. BACKGROUND: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far. OBJEKTIVES: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test). METHODS: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents. RESULTS: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99). CONCLUSION: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.

We used data from the GUIDANCE Study to determine the care of people with type 2 diabetes according to age and accompanying cardiovascular diseases and to assess indicators of overtreatment of glycaemia. The GUIDANCE study was a retrospective, cross-sectional study from 2009–2010 based on the records of 7597 people in France, Belgium, Italy, the Netherlands, Sweden, UK, Ireland and Germany. We analysed the level of metabolic control achieved and blood glucose-lowering medication used in different age groups and in relation to accompanying diseases. 4.459 patients (59.1%) were 65 years or older. Their HbA1c levels were similar to those with

Background Precise blood pressure (BP) measurements are central for the diagnosis of hypertension in clinical and epidemiological studies. The purpose of this study was to quantify the variability in BP associated with arm side, body position, and successive measurements in the setting of a population-based observational study. Additionally, we aimed to evaluate the influence of different measurement conditions on prevalence of hypertension. Methods The sample included 967 men and 812 women aged 45 to 83 years at baseline. BP was measured according to a standardized protocol with oscillometric devices including three sitting measurements at left arm, one simultaneous supine measurement at both arms, and four supine measurements at the arm with the higher BP. Hypertension was defined as systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg. Variability in SBP and DBP were analysed with sex-stratified linear covariance pattern models. Results We found that overall, no mean BP differences were measured according to arm-side, but substantial higher DBP and for men also higher SBP was observed in sitting than in supine position and there was a clear BP decline by consecutive measurement. Accordingly, the prevalence of hypertension depends strongly on the number and scheme of BP measurements taken to calculate the index values. Conclusions Thus, BP measurements should only be compared between studies applying equal measurement conditions and index calculation. Moreover, the first BP measurement should not be used to define hypertension since it overestimates BP. The mean of second and third measurement offers the advantage of better reproducibility over single measurements. Electronic supplementary material The online version of this article (doi:10.1186/s12872-017-0468-7) contains supplementary material, which is available to authorized users.

Aus den Ergebnissen der Deutschen Wirbelsaulenstudie (DWS1), die die Basis der hier vorgestellten DWS-Richtwertestudie (DWS2) darstellen, ist die grundsatzliche Aussage ableitbar, dass auch unterhalb bestimmter Schwellenwerte des Mainz-Dortmunder Dosismodells (MDD) Risiken fur die Entstehung einer bandscheibenbedingten Erkrankung der Lendenwirbelsaule bestehen. In den verwendeten Dosismodellen der DWS1 wurden die Schwellenwerte der Bandscheibendruckkraft, Rumpfvorneigung und Tagesdosis nicht getrennt voneinander, sondern in Kombination variiert. Daher erlaubten die bisherigen Auswertungen der DWS1 keine Aussagen zu Dosismodellen, die durch definierte Absenkung einzelner Eigenschaften des MDD, z. B. der Druckkraft, bei Beibehaltung der ubrigen Eigenschaften gekennzeichnet sind. Ziel der DWS2 ist die wissenschaftlich fundierte Ableitung eines Dosismodells unter Berucksichtigung geeigneter Schwellenwerte. In der DWS2 werden die Schwellenwerte (Bandscheibendruckkraft, Rumpfvorneigung, Tagesdosis) einzeln und anschliesend auch kombiniert variiert. Dabei wird die Anpassungsgute der resultierenden Dosismodelle zur Beschreibung des Dosis-Wirkung-Zusammenhangs auf der Grundlage der kontinuierlichen Dosiswerte anstelle klassierter Daten in der DWS1 und unter Einsatz verschiedener statistischer Methoden [z. B. Akaike-Informationskriterium (AIC), Multi-Modell-Ansatze, fraktionale Polynome] ermittelt. In die Berechnung der Schwellenwerte gingen die Informationen mehrerer gut anpassender, einen breiten Bereich von Schwellenwerten reprasentierender Dosismodelle ein. Unter Einsatz statistischer Mittelungsverfahren (Multi-Modell-Ansatze) liesen sich daraus folgende Schwellenwerte ableiten: eine Bandscheibendruckkraft von 3,2 kN fur Manner und 2,5 kN fur Frauen, ein Rumpfneigungswinkel von 45°, eine Tagesdosis von 2,0 kNh bei Mannern und 0,5 kNh bei Frauen. Weiterhin lies sich eine Verdopplungsdosis des Bandscheibenerkrankungsrisikos von etwa 7 MNh bei Mannern und etwa 3 MNh bei Frauen ermitteln. Die vertiefende Reanalyse der Daten der DWS1 liefert eine wichtige Grundlage zur Beurteilung der Dosis-Wirkung-Beziehung zwischen korperlichen Belastungen und bandscheibenbedingten Erkrankungen. Zunachst sind statistische Unsicherheiten bei der Ableitung von Schwellenwerten sowie die Vereinbarkeit der Studienergebnisse mit den Anforderungen des Berufskrankheitenrechts zu diskutieren, bevor konkrete Folgerungen fur die Berufskrankheit Nr. 2108 gezogen werden konnen.

The aim of this study was to assess the association between the introduction of the nationwide mammography screening program (MSP) and breast cancer surgery rates in Germany 2005-2009. We used nationwide DRG hospitalization files (2005-2009) and analyzed surgery rates for the treatment of invasive and in situ breast cancer in Germany. We used actual numbers of screened women to model the influence of the introduction of the MSP on surgery rates. During 2005 through 2009, the rate of breast-conserving surgery for invasive and in situ breast cancer increased among all age groups. However, rate increases for invasive and in situ breast surgery were largest among women aged 50-69 years (invasive: rate difference [per 100,000] 95.1, 95 % CI 90.7; 99.5; in situ: rate difference 34.4, 95 % CI 32.6; 36.2). Mastectomy rates generally showed little change over time. Conditional on a 70 % participation in the MSP, our model predicts that the estimated increase of mastectomy rates for invasive and in situ breast cancer among women aged 50-69 years during the introductory phase of the MSP would be 4.2 (95 % CI -0.2; 8.6) and 6.1 per 100,000 (95 % CI 5.0; 7.1), respectively. The introduction of the nationwide MSP shows markedly rising rates of breast conserving surgery for women aged 50-69 years with invasive and in situ breast cancer. This increase is expected as a consequence of the first screening round. The model-based estimate for the increase of mastectomy rates, assuming a 70 % MSP participation, is lower than the reported increases observed in MSP in other countries.

Few studies have examined the age-specific use of hysterectomy by indication. The aim of this study was to provide detailed nationwide age-specific prevalence-corrected hysterectomy rates for several indications in Germany, representing a population of 42 million women.Nationwide population-based diagnosis related group data of the years 2005 and 2006 were used to calculate the prevalence-corrected hysterectomy rates by age and indication group.Prevalence-corrected age-standardized hysterectomy rates (any indication) was 362.9 (295.0 for benign diseases of the genital tract and 44.0 for primary malignant tumors of the genital tract) per 100,000 person-year. Corrected hysterectomy rates become increasingly greater than the uncorrected hysterectomy rates, such that they are about 68 % greater for women in the age groups 75-79, 80-84, and 85-89 years. Age-specific hysterectomy rates showed quite different patterns depending on the indication of hysterectomy. For example, hysterectomy rates closely follow the cancer incidence rates up to age 44 for cervical cancer and age 69 for uterine cancer, diverging noticeably in ages thereafter.The prevalence-corrected hysterectomy rates presented in this study provide a more accurate indication of the use of hysterectomy, which has implications in terms of costs and resource allocation. Understanding the role of hysterectomy in treating selected diseases across the age span is also important for patients and doctors as they consult together about an appropriate course of treatment.

Ziel dieser Untersuchung war es zu beurteilen, ob durch die Anwendung der Clampless-off-pump(less OPCAB)-Technik Letalitat und Schlaganfallrate sowie andere schwere Komplikationen in der Koronarchirurgie gesenkt werden konnen. Zwischen Juli 2009 und November 2010 erfassten wir die Daten von 1282 Patienten, die sich einer isolierten Bypassoperation unterziehen mussten, prospektiv in einer Datenbank. In 30,8% der Falle wurden die Prozeduren vollstandig ohne Klemmen der Aorta durchgefuhrt. Dabei wurden die zentral venosen Anastomosen entweder mit dem PAS-Port-System automatisch hergestellt, oder es wurde komplett arteriell ohne das Anlegen von zentralen Anastomosen revaskularisiert. Um fur eine Unausgewogenheit zwischen den Gruppen (Selektionsbias) zu korrigieren, wurde auf der Basis von 15 Variablen, die das Risikoprofil der Patienten abbilden, eine Propensity-Score(PS)-Analyse durchgefuhrt. Letalitat, Schlaganfallrate und weitere Komplikationen sowie Ressourcenverbrauch verglichen wir zwischen der Less-OPCAB- und der konventionellen Gruppe (cCABG). Insgesamt konnten 788 Patienten (394 Paare) erfolgreich gematcht werden. Durch die Less-OPCAB-Technik konnten Letalitat (OR: 0,25, 95%-KI: 0,05–1,17) und Schlaganfallrate (OR: 0,35, 95%-KI: 0,12–0,98) signifikant gesenkt werden. Komplikationen wie Low-output-Syndrom, Langzeitbeatmung oder die Rate der Rethorakotomien waren in der Less-OPCAB-Gruppe ebenfalls reduziert. In dieser retrospektiven Propensity-Score-Analyse senkt die Clampless-OPCAB-Technik Letalitat, Schlaganfallrate und andere Morbiditatsfaktoren in einem nicht selektionierten Kollektiv koronarchirurgischer Patienten.

The aim of this study was to provide population-based German-wide hysterectomy rates based on the national hospitalization file and to estimate the rate of conversion from laparoscopical or vaginal hysterectomy to open abdominal hysterectomy. Nationwide population-based DRG (diagnosis related groups) data of the years 2005 and 2006 were used to calculate hysterectomy rates by indication group and type of surgical approach. Overall 305,015 hysterectomies were performed during the study period (4.5 out of 1,000 women aged 20 years or more). The hysterectomy rate for benign diseases of the genital tract among women aged 20 years or more (3.6 out of 1,000 women) is higher than in Sweden but lower than in the US or Australia. Only 6 and 5% of all hysterectomies were performed by laparoscopically assisted vaginal hysterectomy and laparoscopic hysterectomy, respectively. Twenty-six percent of hysterectomies for benign diseases among women aged 50 years or more included bilateral oophorectomy. 10% of laparoscopical hysterectomies and 1% of vaginal hysterectomies necessitated a conversion to an abdominal hysterectomy. For both types of hysterectomies, the conversion rates were highest for primary malignant genital tract cancer and other cancers compared to the other indication groups. Whereas the conversion rate for laparoscopical hysterectomies increased by age, this rate did not change by age for vaginal hysterectomies. Conversion from laparoscopically or vaginal hysterectomy to open abdominal hysterectomy is associated with the indication and type of hysterectomy started with and is considerably higher for laparoscopic than vaginal hysterectomies.

Since its introduction into the biomedical literature, statistical significance testing (abbreviated as SST) caused much debate. The aim of this perspective article is to review frequent fallacies and misuses of SST in the biomedical field and to review a potential way out of the fallacies and misuses associated with SSTs. Two frequentist schools of statistical inference merged to form SST as it is practised nowadays: the Fisher and the Neyman-Pearson school. The P-value is both reported quantitatively and checked against the alpha-level to produce a qualitative dichotomous measure (significant/nonsignificant). However, a P-value mixes the estimated effect size with its estimated precision. Obviously, it is not possible to measure these two things with one single number. For the valid interpretation of SSTs, a variety of presumptions and requirements have to be met. We point here to four of them: study size, correct statistical model, correct causal model, and absence of bias and confounding. It has been stated that the P-value is perhaps the most misunderstood statistical concept in clinical research. As in the social sciences, the tyranny of SST is still highly prevalent in the biomedical literature even after decades of warnings against SST. The ubiquitous misuse and tyranny of SST threatens scientific discoveries and may even impede scientific progress. In the worst case, misuse of significance testing may even harm patients who eventually are incorrectly treated because of improper handling of P-values. For a proper interpretation of study results, both estimated effect size and estimated precision are necessary ingredients.

Background: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy. Methods: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m−2 over 30 min), oxaliplatin (65 mg m−2) and 5-FU (1500 mg m−2 over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure. Results: Response rates were 19% (95% CI: 6–32%) and 23% (95% CI: 9–37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6–12.4) and 9.9 months (95% CI: 7.5–12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia. Conclusion: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Up to now, evidence about survival of patients with non-small-cell lung cancer treated with radiation therapy alone is only available from clinical studies. The authors analyzed survival experience depending on several prognostic factors from a population-based cancer registry and compared this to survival data from the literature. Between April 1996 and September 1999, 1,696 patients with lung cancer were recruited by the Halle Lung Cancer (HALLUCA) Study. 1,183 patients were diagnosed as having non-small-cell lung cancer, and 188 in clinical stages I–IIIb (15.9%) were treated with radiation therapy alone. The median survival time of all patients was 10.2 months, the 2-year overall survival rate amounted to 15.8%. Besides tumor stage, radiation dose was found to be a statistically significant prognostic factor for survival in univariate analysis. The median survival time was 4.2 months for 66 patients treated with < 50 Gy, 10.7 months for 80 patients treated with 50 to < 60 Gy, and 18.9 months for 42 patients treated with ≥ 60 Gy; the corresponding 2-year overall survival rates were 8.7%, 13.4%, und 35.2%. The significant influence of dose persisted even after adjustment for different confounders in a Cox regression model. Patients treated with 50 to < 60 Gy under a potentially curative therapeutic regimen had a significantly lower survival, compared to patients treated with ≥ 60 Gy. In terms of quality assurance, the large proportion of patients treated with radiation doses below the curative range of ≥ 60 Gy was unexpected.

The dermatologist's procedure was introduced in 1972 as a "procedure of early detection of occupational skin disease" by industrial, agricultural and public-sector employers' liability insurance funds of Germany's statutory occupational accident insurance. To date, it represents the most relevant tool for secondary prevention in industrial dermatology in Germany. According to the intention of this procedure, insured parties who are likely to have an occupational skin disease have to be offered preventive measures and, if necessary, given appropriate treatment to avoid job-loss. In co-operation with the Central Federation of the Industrial Professional Associations, the Task Force on Occupational and Environmental Dermatology of the German Dermatological Society, and the Professional Organisation of German Dermatologists, a study group was constituted in 1999 to improve the traditional dermatologist's procedure. In October 2002 a controlled intervention study was started in North-western Germany to establish the definitive value of the "optimised" dermatologist's procedure. Past, present, and future of this specific procedure are discussed.

Grundgedanke des 1972 eingefuhrten Verfahrens zur Fruherfassung berufsbedingter Hauterkrankungen „Hautarztverfahren“ war es, hauterkrankten Beschaftigten einen Berufsverbleib durch Ausschopfung aller zur Verfugung stehenden berufsdermatologischen Interventionsmasnahmen und eine fruhzeitig eingeleitete adaquate Therapie zu ermoglichen. Das Hautarztverfahren stellt bis heute das fur die Berufsdermatologie wichtigste sekundarpraventive Instrument in der gesetzlichen Unfallversicherung dar. Auf Anregung des Hauptverbandes der gewerblichen Berufsgenossenschaften und mit Beteiligung der Arbeitsgemeinschaft fur Berufs- und Umweltdermatologie und des Berufsverbandes der Deutschen Dermatologen hatte sich 1999 eine Arbeitsgruppe konstituiert, um das bisherige „klassische“ Hautarztverfahren zu optimieren. Im Vordergrund stand dabei das Bemuhen um eine Effizienzsteigerung des Verfahrens. Eine hierzu im Oktober 2002 in Nordwestdeutschland angelaufene kontrollierte Interventionsstudie soll die bessere Umsetzung sekundarer Praventionsmasnahmen durch das „optimierte“ gegenuber dem „klassischen“ Hautarztverfahren belegen. Ziel ist, aus den Studienergebnissen einen konkreten Vorschlag fur die Gestaltung des „optimierten“ Hautarztverfahrens vor seiner bundesweiten Einfuhrung abzuleiten.

Grundgedanke des 1972 eingefuhrten Verfahrens zur Fruherfassung berufsbedingter Hauterkrankungen, des "Hautarztverfahrens", war es, hauterkrankten Beschaftigten einen Berufsverbleib durch 1. Ausschopfung aller zur Verfugung stehenden berufsdermatologischen Interventionsmasnahmen und 2. adaquate Therapie zu ermoglichen. Das Hautarztverfahren stellt bis heute das fur die Berufsdermatologie wichtigste sekundarpraventive Instrument in der gesetzlichen Unfallversicherung dar. Auf Anregung des HVBG und mit Beteiligung der ABD und des BVDD hatte sich 1999 eine Arbeitsgruppe konstituiert, um das bisherige, "klassische" Hautarztverfahren zu optimieren. Im Vordergrund stand dabei das Bemuhen um eine Effizienzsteigerung des Verfahrens. Eine hierzu im Oktober 2002 angelaufene Pilotstudie soll die bessere Umsetzung sekundarer Praventionsmasnahmen durch das "optimierte" gegenuber dem "klassischen" Hautarztverfahren belegen. Es ist das Ziel, aus den Studienergebnissen einen konkreten Vorschlag fur die Gestaltung des "optimierten" Hautarztverfahrens vor seiner bundesweiten Einfuhrung abzuleiten.

Objectives. It is commonly accepted that the standard screening tray is an essential diagnostic test in patch testing supporting the diagnosis of contact dermatitis, the most common type of occupational skin disease (OSD). In this study standard patch-test results of employed persons with an initial report of an OSD were analyzed within 24 occupational groups. Methods. An evaluation was made of employed persons recorded in the Register of Occupational Skin Diseases in Northern Bavaria (Berufskrankheitenregister Haut-Nordbayern; BKH-N) between 1990 and 1999, catering for those standard screening tray allergens tested over the 10-year period. Results. Nickel sulfate was the most common sensitizer (29.5%), showing occupational relevance in only 11% of the cases sensitized. Other common sensitizers were cobalt chloride (13.5%), p-phenylenediamine free base (10.7%), potassium dichromate (9.8%), fragrance mix (5.4%), thiuram mix (4.2%), balsam of Peru (4.0%), chloromethylisothiazolinone/methylisothiazolinone (4.0%), and formaldehyde (4.0%). The most occupationally relevant sensitizers were thiuram mix (71%), epoxy resin (67%), p-phenylenediamine free base (59%), p-phenylenediamine-black-rubber mix/N-isopropyl-N'-phenyl-p-phenylenediamine (53%), potassium dichromate (48%), formaldehyde (38%), chloromethylisothiazolinone/methylisothiazolinone (37%), and mercapto-mix/mercaptobenzothiazole (35%). Occupational groups at risk of acquiring delayed-type sensitization were, in particular, electroplaters, tile setters and terrazzo workers, construction and cement workers, solderers, wood processors, and leather and fur processors. Conclusions. The standard series contributes valuable information and asserts its position in clarifying the causes of OSDs. Based on the study results, the rate of occupationally relevant sensitization to each single allergen is demonstrated, and the difficulties in verifying the occupational relevance are discussed.

Irritant contact dermatitis (ICD), provoked by work materials or workflows, is believed to be a frequent cause of occupational skin disease (OSD). Data of incidence rates of ICD within different occupations are inadequate.We conducted a population-based study to identify occupational groups at risk for irritant and allergic contact dermatitis (ACD).The data are based on all workers' compensation claims reported to our register of OSDs in Northern Bavaria [Berufskrankheitenregister Haut-Nordbayern (BKH-N)], Germany.From 1990 to 1999, 5285 patients had their cases completely assessed and recorded by government-employed physicians. We calculated the incidence rates of ICD and ACD in various occupations, divided into 24 occupational groups, in co-operation with the German State Institute of Labor and Occupation; there were a known total number of employees in each of the occupations. In these groups 3097 (59%) patients with OSD were observed, with an overall annual incidence rate of 4.5 patients per 10,000 workers for ICD, compared with 4.1 patients per 10,000 workers for ACD. The highest ICD annual incidence rates were found in hairdressers (46.9 per 10,000 workers per year), bakers (23.5 per 10,000 workers per year), and pastry cooks (16.9 per 10,000 workers per year); at the same time ICD was the main diagnosis of OSD in pastry cooks (76%), cooks (69%), food processing industry workers and butchers (63%), mechanics (60%), and locksmiths and automobile mechanics (59%). The results of a questionnaire showed frequent skin contact with detergents (52%), disinfectants (24%), and acidic and alkaline chemicals (24%) in the workplace.Based on the incidence data of the BKH-N, this study identified occupational groups with a high risk of ICD. Different frequencies of ICD and ACD within a single group are demonstrated. The frequent usage of detergents is being addressed because of the introduction of German legislation of recent date (the Approved Code of Practice 531 on 'wet work').

Background Human ß-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV) and copy-number variants (CNV) of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case–control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF) cluster copy number (CN), and pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). Results Two groups of PDAC (N=70) and CP (N=60) patients were compared to matched healthy control groups CARLA1 (N=232) and CARLA2 (N=160), respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification. Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively. The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher’s exact test P=0.027), but not between CP and CARLA2 (P=0.867). Conclusion Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.