No Placebo Effect beyond Regression to the Mean on the Six Minute Walk Test in Pulmonary Arterial Hypertension Trials.

In drug studies, patients are often included when the disease activity is high. This will make any treatment appear to lessen disease activity, although the improvement is biased by selection. This effect is known as regression towards the mean (RTM). We aimed at investigating drug trials in Pulmonary Arterial Hypertension (PAH) using the 6-minute walking distance test (6MWD) as a primary outcome for the phenomenon of RTM. An existing registry of 43 open label studies and 23 randomized controlled trials conducted between 1990 and 2009 was used as the data source. Data analysis was carried out for 18 randomized controlled trials (RCTs) and 24 open label studies out of this registry. Data were analyzed for verum and placebo arms of the RCTs separately, as well as for the open label arms. In the verum arms, the overall effect given as 33.2 m (95% CI: 25.7; 40.6]); 6MWD was slightly lower than the effect in the observational studies, with 44.6 m (95% CI: [25.4; 63.8]). After studying and interpreting the data, we found that regression towards the mean plays only a minor role in PAH studies. In particular, placebo effects in the RCTs were negligibly small, with a mean 6MWD of -2.5 m (95% CI: [-9.8; 4.7]) in the placebo arm. Therefore, our analysis indicates that results of non-randomized observational studies can be regarded as valid tools for gaining valid clinical effects in patients with PAH.

Association of patients' pre-therapy strengths and alliance in outpatient psychotherapy: A multilevel growth curve analysis.

OBJECTIVE: Meta-analytic evidence showed robust associations between the alliance in psychotherapeutic dyads and treatment outcomes. Recent studies have indicated that facets of positive mental health are additionally relevant predictors of both the alliance and success of psychotherapy. However, the impact of patients' pre-therapy strengths on the alliance at the beginning and during treatment has been scarcely examined. METHOD: 428 patients (62.4% female, Mage = 40.79), treated by 41 therapists, underwent cognitive behavioral therapy in a German outpatient training and research center. Alliance from patients' perspectives was assessed at the beginning and during treatment. Data were analyzed with multilevel growth curve modeling. RESULTS: Alliance increased during psychotherapy, with a quadratic trajectory best representing this trend on average, p < .001. Pre-therapy strengths were positively related to alliance intercept, b = 0.0537, p < .001. No interaction was found between the included time variables and pre-therapy strengths in the prediction of the alliance slope. CONCLUSION: Positive mental health facets should be considered in psychotherapy research and practice. Future studies may focus on the parallel development of patients' strengths with other process factors in treatment.

Medical error analysis in dermatology according to the reports of the North Rhine Medical Association from 2004 to 2018.

BACKGROUND: Assessment of complaints addressed to the Expert Committee for Medical Malpractice Claims of the North Rhine Medical Association helps to identify quality assurance problems in dermatology. METHODS: 333 dermatological reports (years 2004-2018) were allocated to three five-year intervals in order to show changes of total number of reports and with regard to indications, types of care, defined diagnosis categories, and therapeutic interventions. Statistical analysis was mainly descriptive (SPSS 27). Representative cases are explained in more detail. RESULTS: The number of dermatological reports fell from 119 in the first to 92 reports in the last five-year interval, along with a decline in treatment error rates (43 % and 29 %) despite an increasing number of procedures across disciplines. 104 reports dealt with (supposed) diagnostic errors, 156 with physical or pharmacological therapies, and 73 reports with surgery. The latter had a low treatment error rate (29 %). CONCLUSIONS: In comparison to the number of dermatological treatments in Germany, patient allegations are raised only rarely indicating greater patient satisfaction and/or a lower risk potential in dermatology. Incorrect dosages or device settings, diagnostic errors, and deficits in obtaining informed consent are relevant sources of error as underlined by the presented case reports.

Adverse events and contradictory effects of benzodiazepine in a case with intellectual disability and challenging behaviour.

This study aims to contribute to the knowledge about lacking or contradictory effects of benzodiazepine on hyperaroused or aggressive behaviour in persons with intellectual disability (ID). We conducted a retrospective and natural case study in a person with mild ID and multiple adverse childhood experiences (ACE), using routine diary data consisting of 275 days including 113 consecutive days under benzodiazepine medication. The medication effects were documented as "calm / relaxed", "fretful / distressed" and "sleep / doze". Transitions between these were modelled using Markov chains. Differences in transitions were analysed using Chi-Square test for homogeneity. The results show a significantly reduced stability of mood and increased distressed behaviour under benzodiazepine. This is in line with reports about the effects of psychotropic medication in patients with ID and challenging behaviour. Besides other influences on unexpected medication effects, a possible dissociative identity disorder is discussed as an additional explanation.

The INTREST registry: protocol of a multicenter prospective cohort study of predictors of women's response to integrative breast cancer treatment.

BACKGROUND: Cancer registries usually assess data of conventional treatments and/or patient survival. Beyond that, little is known about the influence of other predictors of treatment response related to the use of complementary therapies (CM) and lifestyle factors affecting patients' quality and quantity of life. METHODS: INTREST is a prospective cohort study collecting register data at multiple German certified cancer centers, which provide individualized, integrative, in- and outpatient breast cancer care. Patient-reported outcomes and clinical cancer data of anticipated N = 715 women with pTNM stage I-III breast cancer are collected using standardized case report forms at the time of diagnosis, after completing neo-/adjuvant chemotherapy, after completing adjuvant therapy (with the exception of endocrine therapy) as well as 1, 2, 5, and 10 years after baseline. Endpoints for multivariable prediction models are quality of life, fatigue, treatment adherence, and progression-based outcomes/survival. Predictors include the study center, sociodemographic characteristics, histologic cancer and comorbidity data, performance status, stress perception, depression, anxiety, sleep quality, spirituality, social support, physical activity, diet behavior, type of conventional treatments, use of and belief in CM treatments, and participation in a clinical trial. Safety is recorded following the Common Terminology Criteria for Adverse Events. DISCUSSION: This trial is currently recruiting participants. Future analyses will allow to identify predictors of short- and long-term response to integrative breast cancer treatment in women, which, in turn, may improve cancer care as well as quality and quantity of life with cancer. TRIAL REGISTRATION: German Clinical Trial Register DRKS00014852 . Retrospectively registered at July 4th, 2018.

Comparison of histomorphometric and radiographic effects of growth guidance with tension-band devices (eight-Plate and FlexTack) in a pig model.

Background and purpose - Temporary hemiepiphysiodesis for growth modulation in skeletally immature patients is a long-known technique. Recently the use of tension-band devices has become popular. This study compares 2 tension-band implants (eight-Plate and FlexTack) regarding their effects on the growth plate.Animals and methods - 12 pigs in 2 equally sized groups (A and B) were investigated. The right proximal medial tibia was treated with either eight-Plate or FlexTack. The left tibia of the same pig was treated with the opposite implant. After 9 weeks all implants were removed. Animals in group B were then hosted for another 5 weeks. Histomorphometric analysis of the growth plate was carried out after 9 and 14 weeks, respectively. Radiographs were taken at implantation, removal, and after 14 weeks.Results - Both tension-band devices achieved a statistically significant and clinically relevant growth inhibition, whereas the effect appeared to be more distinct after the use of FlexTack. Implant-related complications or physeal damage was not observed. After implant removal, rebound phenomenon was radiologically observed in all cases. The growth plates treated with eight-Plate showed a paradox reversal of the zonal distributions, with an increase of the proliferative zones at the previously arrested medial aspect of the physis and a decrease laterally.Interpretation - Both eight-Plate and FlexTack proved to be appropriate devices for growth-guiding treatment. The radiographic evaluation showed a change in angular axes after treatment with each implant, while the correction appeared to be faster with FlexTack. The paradox cartilaginous reaction observed after removal of the eight-Plate might be a histopathological correlate for rebound phenomenon.

Do patients of integrative anthroposophic pediatric inpatient departments differ? Comparative analysis to all pediatric inpatients in Germany considering demographic and clinical characteristics.

BACKGROUND: Integrative medicine (IM) is a patient-centered, evidence-based, therapeutic paradigm which combines conventional and complementary approaches. The use of IM in pediatrics has increased in the past two decades and parents' demand for it is growing. An IM whole systems approach is anthroposophic medicine. Considering the growing demand for integrative approaches in children, it is relevant from a public health perspective to find out which kind of children use IM in Germany and whether they differ from the entirety of pediatric inpatients in Germany. Moreover, it would be interesting to known, whether these patients are willing to travel a longer distance to gain integrative treatment. METHODS: The present study investigates the standard ward documentation datasets of 29,956 patients of all German integrative anthroposophic pediatric inpatient wards from 2005 to 2016 and compares them systematically to collect data of the entirety of all pediatric inpatient wards in Germany. Apart from patients' age and gender, and the ICD-10 admission diagnoses, the geographical catchment area of the hospitals were analyzed. RESULTS: Sociodemographic characteristics of pediatric inpatients in the integrative anthroposophic departments (IAH) did not differ from the entirety of all pediatric inpatients. Regarding clinical characteristics, higher frequencies were found for endocrine, nutritional and metabolic diseases (IAH: 7.24% vs. 2.98%); mental, behavioral, and neurodevelopmental disorders (IAH: 9.83% vs. 3.78%) and nervous diseases (IAH: 8.82% vs. 5.16%) and lower frequencies for general pediatric diseases such as respiratory diseases (IAH: 17.06% vs. 19.83%), digestive diseases (IAH: 3.90% vs. 6.25%), and infectious and parasitic diseases (IAH: 12.88% vs. 14.82%) in comparison to the entirety of all pediatric inpatients in Germany. The IAH showed a broad catchment area, with most patients being from former, Western federal republic of Germany. Large catchment areas (> 100 km) for the IAH are merely covered by severe and chronic diseases. CONCLUSION: Pediatric inpatients of IAH do not differ from the entirety of pediatric inpatients in Germany regarding sociodemographic characteristics but show differences regarding clinical characteristics. Parents are willing to travel further distance to get specialized integrative anthroposophic medical care for children with severe and chronic diseases.

Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study.

INTRODUCTION: Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest because of the potential to guide secondary preventive therapies. Recently, we identified eight microRNAs (miRNAs), which facilitated acute coronary syndrome (ACS) diagnosis. In this study, we aimed to evaluate their potential role as prognostic biomarkers for cardiovascular disease. METHODS: The serum concentrations of eight candidate miRNAs -miR-19a, miR-19b, miR-132, miR-140-3p, miR-142-5p, miR-150, miR-186, and miR-210 were measured in a cohort of 1112 patients with documented CAD-including 430 patients with ACS and 682 patients with stable angina pectoris. Cardiovascular death was the main outcome measure. RESULTS: During a median follow-up of 4.0 years, most miRNAs reliably predicted cardiovascular death in ACS patients. Cox regression analyses indicated that in particular miR-132 (HR 2.85 per 1 SD increase, P = 0.022), miR-140-3p (HR 2.88 per 1 SD increase, P = 0.022), and miR-210 (HR 3.10 per 1 SD increase, P = 0.039) were able to precisely predict cardiovascular death. Circulating miR-132, miR-140-3p, and miR-210 clearly improved various model performance measures, including C-statistics (AUC [area under the receiver-operating characteristic curve] for miR-132: 0.737; AUC for miR-140-3p: 0.756; AUC for miR-210: 0.754). CONCLUSIONS: This is the largest study so far evaluating the prognostic value of circulating miRNAs in cardiovascular disease. Our study shows that single miRNAs derived from peripheral blood predict mortality in secondary prevention settings, and thereby represent valuable biomarkers for risk estimation in CAD.

Reference intervals of plasma homoarginine from the German Gutenberg Health Study.

BACKGROUND: Low circulating homoarginine has been associated with adverse cardiovascular (CV) outcome and mortality in patients at risk and in the general population. The present study aimed to define plasma homoarginine reference intervals from a representative population sample to improve risk stratification between healthy individuals and individuals at risk. METHODS: We determined age- and sex-specific reference intervals for circulating plasma homoarginine in a subgroup of 786 healthy participants (no CV disease or risk factors) of the Gutenberg Health Study. Homoarginine concentrations were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Median EDTA plasma homoarginine concentration was 1.88 [25th; 75th percentile, 1.47; 2.41] µmol/L, with lower concentrations in women (1.77 [1.38; 2.26] µmol/L) than in men (2.01 [1.61; 2.56] µmol/L; p<0.001). Sex-specific 2.5th and 97.5th percentiles of reference intervals were 0.84 and 3.89 µmol/L in women and 0.98 and 4.10 µmol/L in men, respectively. Homoarginine concentrations also depended on age and single nucleotide polymorphisms related to the L-arginine:glycine amidinotransferase gene. CONCLUSIONS: We provide plasma homoarginine reference intervals in men and women of the general population. The determination of homoarginine levels might be favorable for individual risk stratification.

High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular mortality.

AIMS: High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value. METHODS AND RESULTS: We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m², and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION: The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

Impact of timing and combination of different BNT162b2 and ChAdOx1-S COVID-19 basic and booster vaccinations on humoral immunogenicity and reactogenicity in adults.

In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.

The Interpretation of Verbal Probabilities: A Systematic Literature Review and Meta-Analysis.

INTRODUCTION: Verbal probabilities such as "likely" or "probable" are commonly used to describe situations of uncertainty or risk and are easy and natural to most people. Numerous studies are devoted to the translation of verbal probability expressions to numerical probabilities. METHODS: The present work aims to summarize existing research on the numerical interpretation of verbal probabilities. This was accomplished by means of a systematic literature review and meta-analysis conducted alongside the MOOSE-guidelines for meta-analysis of observational studies in epidemiology. Studies were included, if they provided empirical assignments of verbal probabilities to numerical values. RESULTS: The literature search identified 181 publications and finally led to 21 included articles and the procession of 35 verbal probability expressions. Sample size of the studies ranged from 11 to 683 participants and covered a period of half a century from 1967 to 2018. In half of the studies, verbal probabilities were delivered in a neutral context followed by a medical context. Mean values of the verbal probabilities range from 7.24% for the term "impossible" up to 94.79% for the term "definite". DISCUSSION: According to the results, there is a common 'across-study' consensus of 35 probability expressions for describing different degrees of probability, whose numerical interpretation follows a linear course. However, heterogeneity of studies was considerably high and should be considered as a limiting factor.

Low testosterone concentrations and prediction of future heart failure in men and in women: evidence from the large FINRISK97 study.

AIMS: The increased incidence of heart failure in men suggests that endogenous sex hormones might play a role in the development of heart failure, but epidemiological data remain sparse. Here, we evaluated the predictive value of low testosterone levels on future heart failure in the large population-based FINRISK97 study. METHODS AND RESULTS: Baseline serum testosterone concentrations were measured in 7855 subjects (3865 men and 3990 women) of the FINRISK97 study. During a median follow-up (FU) of 13.8 years, a total of 564 heart failure events were recorded. The age-adjusted baseline testosterone levels did not differ significantly between subjects developing incident heart failure during FU and those without incident events during FU (men: 16.6 vs. 17.1 nmol/L, P = 0.75; women: 1.15 vs. 1.17 nmol/L, P = 0.32). Relevant statistically significant correlations of testosterone levels were found with high-density lipoprotein cholesterol levels (R = 0.22; P < 0.001), body mass index (R = -0.23; P < 0.001), and waist-to-hip ratio (R = -0.21; P < 0.001) in men, while statistically significant correlations in women were negligible in effect size. In sex-stratified Cox regression analyses, taking age into account, a quite strong association between low testosterone and incident heart failure was found in men [hazard ratio (HR) 1.51 (95% confidence interval, CI: 1.09-2.10); P = 0.020 for lowest vs. highest quarter], but not in women [HR 0.70 (95% CI: 0.49-0.98); P = 0.086 for lowest vs. highest quarter]. Nevertheless, this association turned non-significant after full adjustment including body mass index and waist-to-hip ratio, and testosterone levels were no longer predictive for incident heart failure-neither in men [HR 0.99 (95% CI: 0.70-1.42); P = 0.77 for lowest vs. highest quarter] nor in women [HR 0.92 (95% CI: 0.64-1.33); P = 0.99 for lowest vs. highest quarter]. Accordingly, Kaplan-Meier analyses did not reveal significant association of testosterone levels with heart failure. CONCLUSIONS: Low levels of testosterone do not independently predict future heart failure.

A pragmatic randomised controlled trial referring to a Personalised Self-management SUPport Programme (P-SUP) for persons enrolled in a disease management programme for type 2 diabetes mellitus and/or for coronary heart disease.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) are two chronic diseases that cause a tremendous burden. To reduce this burden, several programmes for optimising the care for these diseases have been developed. In Germany, so-called disease management programmes (DMPs), which combine components of Disease Management and the Chronic Care Model, are applied. These DMPs have proven effective. Nevertheless, there are opportunities for improvement. Current DMPs rarely address self-management of the disease, make no use of peer support, and provide no special assistance for persons with low health literacy and/or low patient activation. The study protocol presented here is for the evaluation of a programme that addresses these possible shortcomings and can be combined with current German DMPs for T2DM and CHD. This programme consists of four components: 1) Meetings of peer support groups 2) Personalised telephone-based health coaching for patients with low literacy and/or low patient activation 3) Personalised patient feedback 4) A browser-based web portal METHODS: Study participants will be adults enrolled in a DMP for T2DM and/or CHD and living in North Rhine-Westphalia, a state of the Federal Republic of Germany. Study participants will be recruited with the assistance of their general practitioners by the end of June 2021. Evaluation will be performed as a pragmatic randomised controlled trial with one intervention group and one waiting control group. The intervention group will receive the intervention for 18 months. During this time, the waiting control group will continue with usual care and the usual measures of their DMPs. After 18 months, the waiting control group will also receive a shortened intervention. The primary outcome is number of hospital days. In addition, the effects on self-reported health-state, physical activity, nutrition, and eight different psychological variables will be investigated. Differences between values at month 18 and at the beginning will be compared to judge the effectiveness of the intervention. DISCUSSION: If the intervention proves effective, it may be included into the DMPs for T2DM and CHD. TRIAL REGISTRATION: The study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) in early 2019 under the number 00020592. This registry has been affiliated with the WHO Clinical Trials Network ( https://www.drks.de/drks_web/setLocale_EN.do ) since 2008. It is based on the WHO template, but contains some additional categories for which information has to be given ( https://www.drks.de/drks_web/navigate.do?navigationId=entryfields&messageDE=Beschreibung%20der%20Eingabefelder&messageEN=Description%20of%20entry%20fields ). A release and subsequent number assignment only take place when information for all categories has been given.

A Systematic Review and Meta-Analysis on the Survival of Cancer Patients Treated with a Fermented Viscum album L. Extract (Iscador): An Update of Findings.

PURPOSE: We aimed at updating the evidence found in controlled studies addressing general and event-free survival of cancer patients treated with the fermented mistletoe extract Iscador. METHODS: The databases Embase, PubMed, CAMbase, Scopus, AMED and Cochrane were searched for clinical studies on cancer patients treated with Iscador. Quality of studies and risk of bias were evaluated according to the Cochrane guidelines and the Newcastle Ottawa Scale. Outcome data were expressed as hazard ratios (HR) and the respective 95% confidence intervals (CI). Meta-analysis was carried out using a random-effects model. RESULTS: Eighty-two controlled studies met the inclusion criteria, of which 32 with 55 strata provided data for extracting HR and CI. The overall HR was 0.59 (95% CI: [0.53; 0.65], p < 0.0001) in favour of Iscador treatment. Heterogeneity of study results was moderate (I2 = 50.9%; p < 0.0001, τ2 = 0.053). Meta-regression did not reveal significant effects of sample size or study design. However, significant differences were found between cancer entities (p < 0.01), with most pronounced effects in cervical (HR = 0.43) and less pronounced effects in lung cancer (HR = 0.84). CONCLUSIONS: We found almost identical effects on cancer survival based on a broader database of higher quality. However, none of the studies was blinded and, therefore, there might be risk of performance bias. Implications for cancer survivors are as follows: findings indicate that adjuvant treatment of cancer patients with Iscador can be associated with a better survival.

Cardio-Renal Biomarker Soluble Urokinase-Type Plasminogen Activator Receptor Is Associated With Cardiovascular Death and Myocardial Infarction in Patients With Coronary Artery Disease Independent of Troponin, C-Reactive Protein, and Renal Function.

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography-including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow-up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 (P<0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort (P<0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C-reactive protein, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 (P=0.022) in the overall cohort and 2.22 (P=0.005) in the acute coronary syndrome cohort. Conclusions SuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

Iron Metabolism Contributes to Prognosis in Coronary Artery Disease: Prognostic Value of the Soluble Transferrin Receptor Within the AtheroGene Study.

Background Coronary heart disease is a leading cause of mortality worldwide. Iron deficiency, a frequent comorbidity of coronary heart disease, causes an increased expression of transferrin receptor and soluble transferrin receptor levels (sTfR) levels, while iron repletion returns sTfR levels to the normal physiological range. Recently, sTfR levels were proposed as a potential new marker of iron metabolism in cardiovascular diseases. Therefore, we aimed to evaluate the prognostic value of circulating sTfR levels in a large cohort of patients with coronary heart disease. Methods and Results The disease cohort comprised 3423 subjects who had angiographically documented coronary heart disease and who participated in the AtheroGene study. Serum levels of sTfR were determined at baseline using an automated immunoassay (Roche Cobas Integra 400). Two main outcomes were considered: a combined end point of myocardial infarction and cardiovascular death and cardiovascular death alone. During a median follow-up of 4.0 years, 10.3% of the patients experienced an end point. In Cox regression analyses for sTfR levels, the hazard ratio (HR) for future cardiovascular death and/or myocardial infarction was 1.27 (95% CI, 1.11-1.44, P<0.001) after adjustment for sex and age. This association remained significant (HR, 1.23; 95% CI, 1.03-1.46, P=0.02) after additional adjustment for body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, C-reactive protein, and surrogates of cardiac function, size of myocardial necrosis (hs-Tnl), and hemoglobin levels. Conclusions In this large cohort study, sTfR levels were strongly associated with future myocardial infarction and cardiovascular death. This implicates a role for sTfR in secondary cardiovascular risk prediction.

Differential Item Functioning for Boys and Girls in a Screening Instrument for Attention Deficit Hyperactivity Disorder.

Differential item functioning (DIF) indicates differential response probabilities of items for different subgroups. While there is a vast amount of research and literature on DIF in the field of educational screening and career assessment, DIF analysis has hardly been applied in the field of clinical assessment. This paper aims at analyzing the presence of gender related DIF in a cross-sectional survey of children assessed by a structured questionnaire containing items on attention deficit and hyperactivity. A total of 1449 children (mean age: 1.94 ± 0.14 years; 51.2% male) were included. Almost no significant variations in parameters were found between boys and girls. Results based on a Partial Credit Model indicate an absence of DIF in eight out of nine items. Consistent with other studies in attention deficit hyperactivity disorder (ADHD) our results imply that the same level of rating for a symptom has the same meaning for boys and girls.

Verbal Probabilities: Linear or Logistic? - A Regression Analysis Approach.

Verbal probability expressions are quite intuitive and used in a variety of clinical important issues like adverse drug causality appraisal. However, there is insufficient evidence of their numerical meaning and whether they have a linear or logistic relationship with them. We aimed at contributing to answering these questions by means of a comparative regression analysis based on a sample of N=683 participants between 10 and 82 years (mean age 20.33±11.77; median: 18 years) who were asked to numerically rate a given set of sixteen verbal probability phrases on a visual analogue scale. With respect to the explained variance, we found an R2 for the linear model of 0.574 while R2 for the logistic model was only 0.392 indicating a superiority of linear model compared to the logistic model. Although we were able to show that ranked verbal phrases are more likely to behave in a linear that in a logistic way other regression options like the double logistic model should be taken into consideration for further research.