Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Gesundheitsziele zur Stärkung der gesundheitlichen Kompetenz von Bürgern und Patienten

Despite the fact that there still exists little experience with health targets at the national level in Germany there is a growing interest in this management tool in health policy. An initiative for developing health targets at the national level was launched by the German government in December 2000 and is being administered by a platform representing a broad range of participants within the german health system (see other articles in this journal).This initiative, called “gesundheitsziele.de”, reflects the growing awareness not only for the approach of setting and implementing health targets, but for fostering patient orientation for overcoming a lack of quality and a lack of patient and public involvement in the german health sector. A special working group within the initiative was set up in January 2002 to develop health targets strengthening the health competencies of citiziens and patients.The following article outlines the range of goals and targets developed until autumn 2002. The four decisive areas for intervention focussed with the strategy are:improving transparency within the health system, strengthening health competencies of patients and increasing patient orientation of institutions in the health sector,developing patients'rights and improving the management of patients'complaints about medical treatment.     

Multilocus sequence typing of methicillin-resistant Staphylococcus aureus from an area of low endemicity by real-time PCR

A protocol for multilocus sequence typing (MLST) of methicillin-resistant Staphylococcus aureus (MRSA) was adapted to real-time LightCycler System PCR for efficient and rapid amplification of seven housekeeping genes in the same PCR run and real-time detection of the products. The method was evaluated on a representative and well-characterized collection of clinical MRSA isolates (n = 57) obtained from an area of low endemicity. Twenty sequence types (STs) and nine clonal complexes were identified. Combining STs and the staphylococcal cassette chromosome mec (SCCmec) type identified 27 different genotypes, and type IV SCCmec was present in 11 different STs. The presence of the Panton Valentine leukocidin (PVL) genes was found in isolates of four different STs. Eleven different STs were found among the community-acquired as well as among the hospital-acquired MRSA. The genetic heterogeneity was also denoted by pulsed-field gel electrophoresis analysis that showed 24 different pulsotypes among the 57 MRSA isolates. The presence of more than one different type of SCCmec in the same ST indicates that the MRSA clones have arisen at several occasions in the same genetic background by independent acquisition of SCCmec into methicillin-sensitive strains. This circumstance shows the importance of combining MLST data with SCCmec-typing results when investigating the origins of MRSA.     

Stoffwechseluntersuchungen unter ergometrischer Belastung bei total duodenopankreatektomierten Patienten

Zusammenfassung Ein Jahr nach totaler Duodenopankmatektomie wurde bei 6 Patienten die exokrine Pankreainsuffizienz geprüft. Diese kann durch orale Gabe von wenigstens 10 g Pankreatin kompensiert werden. Gegenüber 7 Normalpersonen und 6 Typ 1-Diabetikern hatten die Duodenopankreatektomierten unter körperlicher Belastung höhere arterielle Spiegel von Lactat und freiem Glycerin als Ausdruck einer gestörten hepatischen Gluconeogenese bei fehlendem pankreatischem Glucagon. Ihre körperliche Leistungsfähigkeit war auffallend schlecht. Catecholamine stiegen unter körperlicher Belastung nur gering an, Wachstumshormone gar nicht. Diese Resultate sprechen gegen die totale Duodenopankreatektomie als Therapie der chronischen Pankreatitis.

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Metabolic investigations under ergometric strain in patients with total duodenopancreatectomy

Summary One year after total duodenopancreatectomy a clinical and laboratory evaluation including exhaustive bicycle ergometry was performed in 6 male patients. The insufficiency of the exocrine pancreas can be compensated by at least 10 g pankreatin per day. During physical exercise patients had higher arterial values of lactate and free glycerol after duodenopancreatectomy than 7 healthy individuals and 6 diabetic patients type 1. This metabolic overreaction was due to a deficiency of pancreatic glucagon and resulted in an impaired hepatic gluconeogenesis. There was no detectable increase in growth hormones and only a small one in catecholamines. The physical condition of patients after duodenopancreatectomy was clearly worse.

Diese Arbeit ist Herrn Prof. Dr. Dr. h.c. Hans Erhard Bock zum Geburtstag gewidmet     

Which implications for obesity prevention can be offered by the KiGGS follow-up study?

From 2003?C2006, the health status of 17,641 girls and boys was comprehensively assessed by interview and medical examinations in the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Therewith, data exists for a broad spectrum of health relevant questions in childhood and adolescence, including indicators, determinants and consequences of obesity. As part of the health monitoring system of the Robert Koch Institute, KiGGS is being continued as a longitudinal study. This enables the observation of health development of children and adolescents up to adulthood as well as the detection of changes in behavior and circumstances within this population. This offers many new perspectives for analyses, whose findings may be helpful for the prevention of obesity. Current insights and future perspectives are discussed.     

Psychische Gesundheit von Jugendlichen in Deutschland

Many children and adolescents in Germany grow up in families with a migration background. Different cultural, religious, and linguistic backgrounds have an influence on their behavior in various ways. Health status can be affected both negatively and positively by a migration background. The aim of this study was to analyze associations between migration background and self-reported psychological problems. In addition, it was tested whether country of origin had a differential effect on the associations found. Because of its migration-specific approach, the baseline survey (2003–2006) of the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS) offers a solid basis for migrant-specific analyses. Self-reported mental health problems were assessed using the Strengths and Difficulties Questionnaire (SDQ), which was completed by 6,719 adolescents aged 11–17 years. Adolescents with a two-sided migration background (i.e., both parents) reported higher SDQ total difficulties scores compared with adolescents without a migration background (16.9 vs 11.5?%) or those with a one-sided migration background (16.9 vs 11.3?%). Adolescents with a Turkish background had higher odds (boys: OR 2.0; 95?%CI 1.3–3.2; girls: OR 2.0; 95?%CI 1.2–3.4) of reporting mental health problems than adolescents without a migration background. Also, girls with a migration background from Western Europe, the USA or Canada had higher odds (OR 2.2; 95?%CI 1.3–3.6). In some cases, adjusting for socioeconomic status led to insignificant associations with regard to the country of origin. The findings underline the importance of migrant-specific and culture-sensitive prevention, which also takes the environment and culture-specific characteristics into account.     

Differentialdiagnose kavernöser Lungenstrukturen

Zusammenfassung Der 56-j?hrige Mann klagte seit ca. vier Wochen über Husten mit rostbraunem Auswurf, Kraftlosigkeit und über einen Gewichtsverlust von ca. 15 kg. An Vorerkrankungen waren ein Herzinfarkt, 2 Lungenembolien und ein Ulcus cruris des rechten Unterschenkels bekannt. Die k?rperliche Untersuchung zeigte einen reduzierten Allgemeinzustand, ein abgeschw?chtes, aber vesikul?res Atemger?usch über allen Lungenabschnitten; au?erdem fiel ein entzündlich ger?tetes Ulcus am rechten Kn?chel auf. Im Labor fanden sich Entzündungszeichen (Leukozytose, CRP, BSG-Erh?hung). Die Thoraxaufnahme (p.a.) lie? im Bereich des linken Lungenoberfeldes eine ca. 7,5 cm gro?e Kaverne erkennen. In der Phlebographie wurde eine frische Thrombose aller dreier Unterschenkelfaszikel sowie ein Zustand nach Thrombose der V. poplitea, femoralis und iliaca mit ausgepr?gtem Kollateralkreislauf über oberfl?chliche Venen nachgewiesen. Bei Verdacht auf Lungentuberkulose wurde zun?chst eine 4-fach Therapie eingeleitet. Zus?tzlich wurde die tiefe Beinvenenthrombose mit intraven?ser Heparingabe (zun?chst 25.000 i.E. über 24 h) therapiert. In der Bronchoskopie ergaben sich weder mikroskopisch noch kulturell Hinweise für eine Lungentuberkulose. Innerhalb von zwei Wochen konnte eine fast vollst?ndige Rückbildung der Kaverne erreicht werden. Die ursprüngliche Arbeitshypothese einer tuberkul?sen Kaverne war aufgrund der raschen Rückbildung und des fehlenden Nachweises von Mykobakterien unwahrscheinlich geworden. Wegen eines weiteren klinisch typischen thrombembolischen Ereignisses wurde ein CT des kleinen Beckens angefertigt, in dem eine ausgedehnte Thrombosierung der V. cava bis zum Abgang der Nierenvenen zur Darstellung kam. Es handelte sich in diesem Fall um die Kaverne einer einschmelzenden Infarktpneumonie.     

Methylenetetrahydrofolate reductase gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B12 levels and the extent of coronary artery disease

The question of whether mild hyperhomocysteinemia is a risk factor for coronary artery disease (CAD) has long been debated and is still unclear. We investigated whether there is a link between methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms or plasma homocysteine and CAD. This is a case-control study that included 2,121 consecutive patients (cases) with angiographically proved CAD and 617 patients without CAD (controls). MTHFR gene C677T and A1298C polymorphisms, plasma homocysteine, folate, and vitamin B(12) concentrations were determined and coronary angiography was performed in all subjects. The distribution of MTHFR gene C677T genotypes in patients (or controls) was: CC-genotype in 915 cases, 43.1% (266 controls, 43.1%); CT-genotype in 955 cases, 45.0%, (283 controls, 45.9%); and TT-genotype in 251 cases, 11.9% (68 controls, 11.0%) (p = 0.84). The distribution of MTHFR gene A1298C genotypes in patients (or controls) was: AA-genotype in 973 cases, 45.9% (281 controls, 45.5%); AC-genotype in 905 cases, 42.7% (284 controls, 46.0%); and CC-genotype in 243 cases, 11.4% (52 controls, 8.5%) (p = 0.07). Patients with CAD had higher levels of plasma homocysteine (12.9 +/- 5.1 vs 11.9 +/- 4.5 micromol/L, p <0.001) and lower levels of folate (9.5 +/- 3.1 vs 9.9 +/- 3.8 ng/ml, p = 0.008) than controls. After adjustment for other risk factors for CAD, plasma homocysteine (p = 0.89), MTHFR gene C677T (p = 0.38), or A1298C polymorphisms (p = 0.13) were not independent correlates of CAD. This study demonstrated that MTHFR gene C677T or A1298C polymorphisms are not associated with the presence of angiographic CAD. Although there is an apparent association between elevated levels of homocysteine and CAD, this association is not independent of conventional cardiovascular risk factors.