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Objective: Valid knowledge about risk stratification is essential for the development of preventive approaches to reduce restraints., Methods:   This retrospective, monocentric study examined all 248 restraining measures used on 79 patients of a university psychiatric department in 2015. Eight institutional and seven patient-related factors were statistically calculated using logistic regression analysis and matched pairs., Results: A statistically significant increased probability of fixation was found in connection with a lower number of nurses per patient, a higher number of patients admitted by law, lower professional experience of nurses and in the nursing late shift as well as when admission occurred via emergency medical service., Conclusion: Based on the results, possible preventive organizational measures are elaborated and preconditions for a prospective evaluation of the complex factors influencing coercive measures are discussed., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Aim: To propose a framework for consistently applying the 2018 periodontal status classification scheme to epidemiological surveys (Application of the 2018 periodontal status Classification to Epidemiological Survey data, ACES)., Proposed Framework: We specified data requirements and workflows for either completed or planned epidemiological surveys, utilizing commonly collected measures of periodontal status (clinical attachment levels [CAL], probing depths, bleeding on probing), as well as additional necessary variables for the implementation of the 2018 periodontal status classification (tooth loss due to periodontitis and complexity factors). Following detailed instructions and flowcharts, survey participants are classified as having periodontal health, gingivitis or periodontitis. Rates of edentulism must also be reported. In cases of periodontitis, instructions on how to compute the stage and extent are provided. Assessment of grade can be derived from CAL measurements (or from radiographic alveolar bone loss data) in relation to root length and the participant's age., Conclusions: ACES is a framework to be used in epidemiological studies of periodontal status that (i) have been completed, and in which stage and grade according to the 2018 classification are inferred retroactively, or (ii) are being planned. Consistent use of the proposed comprehensive approach will facilitate the comparability of periodontitis prevalence estimates across studies., (© 2024 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Objectives: Gastroesophageal reflux disease (GERD) occurs frequently in patients with SSc. We investigated whether the presence of GERD and/or the use of anti-acid therapy, specifically proton-pump inhibitors (PPIs), are associated with long-term outcomes, especially in SSc-associated interstitial lung disease (SSc-ILD)., Methods: We retrospectively analysed patients with SSc and SSc-ILD from the German Network for Systemic Sclerosis (DNSS) database (2003 onwards). Kaplan-Meier analysis compared overall survival (OS) and progression-free survival (PFS) in patients with GERD vs without GERD (SSc and SSc-ILD), and PPI vs no PPI use (SSc-ILD only). Progression was defined as a decrease in either percentage predicted forced vital capacity of ≥10% or single-breath diffusing capacity for carbon monoxide of ≥15%, or death., Results: It was found that 2693/4306 (63%) registered patients with SSc and 1204/1931 (62%) with SSc-ILD had GERD. GERD was not associated with decreased OS or decreased PFS in patients in either cohort. In SSc-ILD, PPI use was associated with improved OS vs no PPI use after 1 year [98.4% (95% CI: 97.6, 99.3); n = 760 vs 90.8% (87.9-93.8); n = 290] and after 5 years [91.4% (89.2-93.8); n = 357 vs 70.9% (65.2-77.1); n = 106; P < 0.0001]. PPI use was also associated with improved PFS vs no PPI use after 1 year [95.9% (94.6-97.3); n = 745 vs 86.4% (82.9-90.1); n = 278] and after 5 years [66.8% (63.0-70.8); n = 286 vs 45.9% (39.6-53.2); n = 69; P < 0.0001]., Conclusion: GERD had no effect on survival in SSc or SSc-ILD. PPIs improved survival in patients with SSc-ILD. Controlled, prospective trials are needed to confirm this finding., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: The aims of this study were to determine the frequency of oral health-related quality of life (OHRQoL) impairment in a national representative sample of 8 to 9 year olds in Germany and to evaluate the impact of orthodontic treatment need., Methods: Data were collected in the Sixth German Oral Health Study (Sechste Deutsche Mundgesundheitsstudie, DMS 6) and subjects were sampled using a multistage sampling technique. OHRQoL was measured with a modified version of the 5‑item Oral Health Impact Profile (OHIP-5) which was administered in a computer-assisted personal interview. Children were also examined for malocclusion and orthodontic treatment need., Results: In all, 1892 children aged 8-9 years were invited to take part. Finally, data of 705 children (48.6% female) could be included in the analysis. The OHIP‑5 mean was 1.3 (±2.0). There was no relevant influence from age and gender on the OHIP‑5 summary scores (r < 0.10), but the summary scores differed when analyzed separately regarding orthodontic treatment need or no orthodontic treatment need (1.5 ± 2.0 vs. 1.2 ± 1.9, p = 0.020). Nevertheless, the level appears to be low., Conclusions: Malocclusions with orthodontic treatment need have an influence on OHRQoL., (© 2022. The Author(s).)

Purpose: The aim of this study was (1) to complete and update the oral-epidemiological data situation in Germany (descriptive epidemiology) and (2) to determine the need for orthodontic treatment provision based on the epidemiological data situation (health care epidemiology in the form of demand research)., Methods: For this purpose, a longitudinal oral-epidemiological study and social science survey with a primary focus on tooth and jaw misalignment was conducted at a nationally representative level on 705 8‑ and 9‑year-old children across Germany., Results: The methodological principles of the oral-epidemiological study are described, with a focus on the calibration and reliability assessment results from the study dentists, sample weighting, a survey of nonrespondents to estimate the extent of the external validity of the study results, a description of the study participants, and realized cases, as well as information pertaining to the response rate and utilization., Conclusion: Based on the conducted analyses, it can be assumed that the examined 8‑ and 9‑year-old study participants are representative of the statistical population in Germany., (© 2023. The Author(s).)

Purpose: Current population-wide data on the prevalence of malocclusions in 8‑ and 9‑year-old children in Germany are not available. Therefore, the primary objective of this study was to collect data on the prevalence of malocclusions in 8‑ and 9‑year-old children in Germany. The secondary objective of this study was to use this information to derive the need for orthodontic care provision., Methods: This is an oral-epidemiological investigation and social science survey at the national level with a focus on tooth and jaw misalignment. The investigation took place between January and March 2021 at 16 study centers across Germany. All relevant data were available for the 705 study participants and were included in the statistical analysis., Results: Overbite was the most common finding with 88.9%. Also widespread were crowding, with at least 60.9%, and lack of space, with a share of 30.9%. All other indication groups had a share below 10%. Rare (< 1%) were buccal and lingual occlusions and craniofacial abnormalities. The most severe forms of disease (Orthodontic Indication Group [Kieferorthopädische Indikationsgruppen, KIG] grade 5) were overbite (3.2%), open bite malocclusion (1.0%), undershot (0.6%), and craniofacial abnormalities (0.4%). The proportion of study participants who required orthodontic treatment, in accordance with statutory health insurance provider guidelines, was 40.4%. The proportion of study participants in principle requiring orthodontic treatment for medical reasons was 97.5%. Systemic differences in the need for orthodontic care provision relating to gender, region, or social status were not identified., Conclusion: In general, the need for care provision identified in the orthodontic indication groups corresponds to that shown in previous studies. This suggests that the need for orthodontic treatment in Germany has remained stable over the years., (© 2022. The Author(s).)

Purpose: The aim of the present study was to compare the malocclusion indices KIG (Kieferorthopädische Indikationsgruppen, Orthodontic Indication Groups), ICON (Index of Complexity, Outcome and Need), and mIOTN (modified Index of Orthodontic Treatment Need) regarding differences in malocclusion prevalence and their assessment of orthodontic treatment need in German 8‑ to 9‑year-old children of the Sixth German Oral Health Study (Deutsche Mundgesundheitsstudie, DMS 6)., Methods: The necessary data for the calculation of the KIG, mIOTN, and ICON were collected by a dentist as part of a clinical orthodontic examination during the field phase of the DMS 6 and by a subsequent digital orthodontic model-analytical evaluation of intraoral scans of the dental arches and the occlusal situation in habitual occlusion., Results: Prevalence, severity, and treatment need of tooth and jaw misalignments differed in part considerably depending on the index used for assessment. On the other hand, there were several outcomes which yielded quite similar results for the different indices used, such as orthodontic treatment need, which ranged from 40.4% (KIG) over 41.6% (ICON) to 44.2% (mIOTN). Interestingly, orthodontic treatment need for the individual subject could differ considerably, when assessed using different indices., Conclusions: In general, the results show that the mIOTN is much more conservative in assessing malocclusion prevalences often being smaller than those derived by KIG or ICON. In contrast, KIG and ICON often yield similar prevalences with certain distinct differences due to discrepancies in the respective definitions and also clearly differentiate between treatment possibility and arbitrarily determined treatment need., (© 2023. The Author(s).)

Objectives: To systematically review the prevalence of bacteraemia, triggered by dental intervention and home oral hygiene practices, in children. The network meta-analysis (NMA) quantitatively compared the risk of bacteraemia triggered by dental extractions and home and professional cleaning procedures., Materials and Methods: Clinical trials with the outcome "bacteraemia in children" were searched. The NMA was performed using the frequentist weighted least-squares approach comparing the odds ratios (OR) of different interventions., Results: Among 11 of 13 studies, dental treatment was performed under general anaesthesia. In 2,381 patients, bacteraemia occurred in 38.7%-56% patients following single-tooth extractions, in 22%-46% after manual toothbrushing (MTB), and in 26%-78% after power toothbrushing (PTB). When MTB was set as the reference (OR 1), rubber cup polishing showed a slightly higher risk (OR 1.26) of bacteraemia. PTB presented a higher risk (OR 1.79-2.27) than with single-tooth extractions (OR 1.55) but lower than that with multiple extractions (OR 2.55)., Conclusion: Daily use of MTB and routine professional cleaning were associated with the lowest risk of developing bacteraemia in children with gingivitis, almost as much as with a single-tooth extractions. Improved plaque control with PTB increased the risk of bacteraemia. There is limited evidence on gingivitis-free and systemically-diseased children., (© 2021 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Background: Anaemia is common among cancer patients and they may require red blood cell transfusions. Erythropoiesis-stimulating agents (ESAs) and iron might help in reducing the need for red blood cell transfusions. However, it remains unclear whether the combination of both drugs is preferable compared to using one drug., Objectives: To systematically review the effect of intravenous iron, oral iron or no iron in combination with or without ESAs to prevent or alleviate anaemia in cancer patients and to generate treatment rankings using network meta-analyses (NMAs)., Search Methods: We identified studies by searching bibliographic databases (CENTRAL, MEDLINE, Embase; until June 2021). We also searched various registries, conference proceedings and reference lists of identified trials., Selection Criteria: We included randomised controlled trials comparing intravenous, oral or no iron, with or without ESAs for the prevention or alleviation of anaemia resulting from chemotherapy, radiotherapy, combination therapy or the underlying malignancy in cancer patients., Data Collection and Analysis: Two review authors independently extracted data and assessed risk of bias. Outcomes were on-study mortality, number of patients receiving red blood cell transfusions, number of red blood cell units, haematological response, overall mortality and adverse events. We conducted NMAs and generated treatment rankings. We assessed the certainty of the evidence using GRADE., Main Results: Ninety-six trials (25,157 participants) fulfilled our inclusion criteria; 62 trials (24,603 participants) could be considered in the NMA (12 different treatment options). Here we present the comparisons of ESA with or without iron and iron alone versus no treatment. Further results and subgroup analyses are described in the full text. On-study mortality We estimated that 92 of 1000 participants without treatment for anaemia died up to 30 days after the active study period. Evidence from NMA (55 trials; 15,074 participants) suggests that treatment with ESA and intravenous iron (12 of 1000; risk ratio (RR) 0.13, 95% confidence interval (CI) 0.01 to 2.29; low certainty) or oral iron (34 of 1000; RR 0.37, 95% CI 0.01 to 27.38; low certainty) may decrease or increase and ESA alone (103 of 1000; RR 1.12, 95% CI 0.92 to 1.35; moderate certainty) probably slightly increases on-study mortality. Additionally, treatment with intravenous iron alone (271 of 1000; RR 2.95, 95% CI 0.71 to 12.34; low certainty) may increase and oral iron alone (24 of 1000; RR 0.26, 95% CI 0.00 to 19.73; low certainty) may increase or decrease on-study mortality. Haematological response We estimated that 90 of 1000 participants without treatment for anaemia had a haematological response. Evidence from NMA (31 trials; 6985 participants) suggests that treatment with ESA and intravenous iron (604 of 1000; RR 6.71, 95% CI 4.93 to 9.14; moderate certainty), ESA and oral iron (527 of 1000; RR 5.85, 95% CI 4.06 to 8.42; moderate certainty), and ESA alone (467 of 1000; RR 5.19, 95% CI 4.02 to 6.71; moderate certainty) probably increases haematological response. Additionally, treatment with oral iron alone may increase haematological response (153 of 1000; RR 1.70, 95% CI 0.69 to 4.20; low certainty). Red blood cell transfusions We estimated that 360 of 1000 participants without treatment for anaemia needed at least one transfusion. Evidence from NMA (69 trials; 18,684 participants) suggests that treatment with ESA and intravenous iron (158 of 1000; RR 0.44, 95% CI 0.31 to 0.63; moderate certainty), ESA and oral iron (144 of 1000; RR 0.40, 95% CI 0.24 to 0.66; moderate certainty) and ESA alone (212 of 1000; RR 0.59, 95% CI 0.51 to 0.69; moderate certainty) probably decreases the need for transfusions. Additionally, treatment with intravenous iron alone (268 of 1000; RR 0.74, 95% CI 0.43 to 1.28; low certainty) and with oral iron alone (333 of 1000; RR 0.92, 95% CI 0.54 to 1.57; low certainty) may decrease or increase the need for transfusions. Overall mortality We estimated that 347 of 1000 participants without treatment for anaemia died overall. Low-certainty evidence from NMA (71 trials; 21,576 participants) suggests that treatment with ESA and intravenous iron (507 of 1000; RR 1.46, 95% CI 0.87 to 2.43) or oral iron (482 of 1000; RR 1.39, 95% CI 0.60 to 3.22) and intravenous iron alone (521 of 1000; RR 1.50, 95% CI 0.63 to 3.56) or oral iron alone (534 of 1000; RR 1.54, 95% CI 0.66 to 3.56) may decrease or increase overall mortality. Treatment with ESA alone may lead to little or no difference in overall mortality (357 of 1000; RR 1.03, 95% CI 0.97 to 1.10; low certainty). Thromboembolic events We estimated that 36 of 1000 participants without treatment for anaemia developed thromboembolic events. Evidence from NMA (50 trials; 15,408 participants) suggests that treatment with ESA and intravenous iron (66 of 1000; RR 1.82, 95% CI 0.98 to 3.41; moderate certainty) probably slightly increases and with ESA alone (66 of 1000; RR 1.82, 95% CI 1.34 to 2.47; high certainty) slightly increases the number of thromboembolic events. None of the trials reported results on the other comparisons. Thrombocytopenia or haemorrhage We estimated that 76 of 1000 participants without treatment for anaemia developed thrombocytopenia/haemorrhage. Evidence from NMA (13 trials, 2744 participants) suggests that treatment with ESA alone probably leads to little or no difference in thrombocytopenia/haemorrhage (76 of 1000; RR 1.00, 95% CI 0.67 to 1.48; moderate certainty). None of the trials reported results on other comparisons. Hypertension We estimated that 10 of 1000 participants without treatment for anaemia developed hypertension. Evidence from NMA (24 trials; 8383 participants) suggests that treatment with ESA alone probably increases the number of hypertensions (29 of 1000; RR 2.93, 95% CI 1.19 to 7.25; moderate certainty). None of the trials reported results on the other comparisons., Authors' Conclusions: When considering ESAs with iron as prevention for anaemia, one has to balance between efficacy and safety. Results suggest that treatment with ESA and iron probably decreases number of blood transfusions, but may increase mortality and the number of thromboembolic events. For most outcomes the different comparisons within the network were not fully connected, so ranking of all treatments together was not possible. More head-to-head comparisons including all evaluated treatment combinations are needed to fill the gaps and prove results of this review., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Esophageal perforation is associated with high morbidity and mortality. In addition to surgical treatment, endoscopic endoluminal stent placement and endoscopic vacuum therapy (EVT) are established methods in the management of this emergency condition. Although health-related quality of life (HRQoL) is becoming a major issue in the evaluation of any therapeutic intervention, not much is known about HRQoL, particularly in the long-term follow-up of patients treated for non-neoplastic esophageal perforation with different treatment strategies. The aim of this study was to evaluate patients' outcome after non-neoplastic esophageal perforation with focus on HRQoL in the long-term follow-up., Methods: Patients treated for non-neoplastic esophageal perforation at the University Hospital Cologne from January 2003 to December 2014 were included. Primary outcome and management of esophageal perforation were documented. Long-term quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI), the Health-Related Quality of Life Index (HRQL) for patients with gastroesophageal reflux disease (GERD), and the European Organization for Research and Treatment of Cancer (EORTC) questionnaires for general and esophageal specific QoL (QLQ-C30 and QLQ-OES18)., Results: Fifty-eight patients were included in the study. Based on primary treatment, patients were divided into an endoscopic (n = 27; 46.6%), surgical (n = 20; 34.5%), and a conservative group (n = 11; 19%). Short- and long-term outcome and quality of life were compared. HRQoL was measured after a median follow-up of 49 months. HRQoL was generally reduced in patients with non-neoplastic esophageal perforation. Endoscopically treated patients showed the highest GIQLI overall score and highest EORTC general health status, followed by the conservative and the surgical group., Conclusion: HRQoL in patients with non-neoplastic esophageal perforation is reduced even in the long-term follow-up. Temporary stent or EVT is effective and provides a good alternative to surgery, not only in the short-term but also in the long-term follow-up., (© 2021. The Author(s).)

Background: Mortality after ST-elevation myocardial infarction (STEMI) is dependent from best-medical treatment after initial event., Objectives: Determining the impact of prescription of guideline-recommended therapy after STEMI in two cohorts, patients with and without history of arterial hypertension, on survival., Methods: 1,025 patients of the Cologne Infarction Model registry with invasively adjudicated STEMI were dichotomized according to their history of arterial hypertension. We recorded prescription rates and dosing of RAS-inhibitors, β-blockers and statins in all patients. The primary outcome was all-cause death. Mean follow-up was 2.5 years., Results: Mean age was 64 ± 13 years, 246 (25%) were women. 749 (76%) patients had a history of hypertension. All-cause mortality was 24.2%, 30-day and 1-year mortality was 11.3% and 16.6%, respectively. History of hypertension correlated with lower mortality (hazard ratio [HR], @30 days: 0.41 [0.27-0.62], @1 year: 0.37 [0.26-0.53]). After adjusting for age, sex, Killip-class, diabetes mellitus, body-mass index, kidney function and statin prescription at discharge 1-year mortality HR was 0.24 (0.12-0.48). At discharge, prescription rates for RAS-inhibitors, β-blockers and statins, as well as individual dosing and long-term persistence of RAS-inhibitors were higher in patients with history of hypertension. On the same lines, prescription rates for RAS-inhibitors, β-blockers and statins at discharge correlated significantly with lower mortality regardless of history of hypertension., Conclusion: Patients with history of hypertension show higher penetration of guideline recommended drug therapy after STEMI, which may contribute to better survival. Better tolerance of β-blockers and RAS-inhibitors in patients with history of hypertension, not hypertension itself, likely explains these differences in prescription and dosing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoffmann, Fassbender, Zander, Ulbrich, Kuhr, Adler, Halbach and Reuter.)

Introduction: Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose., Objective: This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder., Methods: A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers' product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031)., Results: From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of -0.06 (-0.16 to 0.04) and -0.06 (-0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis., Conclusion: Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs., (© 2021 S. Karger AG, Basel.)

Background: About 70% to 80% of adults with cancer experience chemotherapy-induced nausea and vomiting (CINV). CINV remains one of the most distressing symptoms associated with cancer therapy and is associated with decreased adherence to chemotherapy. Combining 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists with corticosteroids or additionally with neurokinin-1 (NK₁) receptor antagonists is effective in preventing CINV among adults receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Various treatment options are available, but direct head-to-head comparisons do not allow comparison of all treatments versus another.  OBJECTIVES: • In adults with solid cancer or haematological malignancy receiving HEC - To compare the effects of antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids on prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting in network meta-analysis (NMA) - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy • In adults with solid cancer or haematological malignancy receiving MEC - To compare whether antiemetic treatment combinations including NK₁ receptor antagonists, 5-HT₃ receptor antagonists, and corticosteroids are superior for prevention of acute phase (Day 1), delayed phase (Days 2 to 5), and overall (Days 1 to 5) chemotherapy-induced nausea and vomiting to treatment combinations including 5-HT₃ receptor antagonists and corticosteroids solely, in network meta-analysis - To generate a clinically meaningful treatment ranking according to treatment safety and efficacy SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings, and study registries from 1988 to February 2021 for randomised controlled trials (RCTs)., Selection Criteria: We included RCTs including adults with any cancer receiving HEC or MEC (according to the latest definition) and comparing combination therapies of NK₁ and 5-HT₃ inhibitors and corticosteroids for prevention of CINV., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. We expressed treatment effects as risk ratios (RRs). Prioritised outcomes were complete control of vomiting during delayed and overall phases, complete control of nausea during the overall phase, quality of life, serious adverse events (SAEs), and on-study mortality. We assessed GRADE and developed 12 'Summary of findings' tables. We report results of most crucial outcomes in the abstract, that is, complete control of vomiting during the overall phase and SAEs. For a comprehensive illustration of results, we randomly chose aprepitant plus granisetron as exemplary reference treatment for HEC, and granisetron as exemplary reference treatment for MEC., Main Results: Highly emetogenic chemotherapy (HEC) We included 73 studies reporting on 25,275 participants and comparing 14 treatment combinations with NK₁ and 5-HT₃ inhibitors. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 704 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with aprepitant + granisetron. Evidence from NMA (39 RCTs, 21,642 participants; 12 treatment combinations with NK₁ and 5-HT₃ inhibitors) suggests that the following drug combinations are more efficacious than aprepitant + granisetron for completely controlling vomiting during the overall treatment phase (one to five days): fosnetupitant + palonosetron (810 of 1000; RR 1.15, 95% confidence interval (CI) 0.97 to 1.37; moderate certainty), aprepitant + palonosetron (753 of 1000; RR 1.07, 95% CI 1.98  to 1.18; low-certainty), aprepitant + ramosetron (753 of 1000; RR 1.07, 95% CI 0.95 to 1.21; low certainty), and fosaprepitant + palonosetron (746 of 1000; RR 1.06, 95% CI 0.96 to 1.19; low certainty).  Netupitant + palonosetron (704 of 1000; RR 1.00, 95% CI 0.93 to 1.08; high-certainty) and fosaprepitant + granisetron (697 of 1000; RR 0.99, 95% CI 0.93 to 1.06; high-certainty) have little to no impact on complete control of vomiting during the overall treatment phase (one to five days) when compared to aprepitant + granisetron, respectively.  Evidence further suggests that the following drug combinations are less efficacious than aprepitant + granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): aprepitant + ondansetron (676 of 1000; RR 0.96, 95% CI 0.88 to 1.05; low certainty), fosaprepitant + ondansetron (662 of 1000; RR 0.94, 95% CI 0.85 to 1.04; low certainty), casopitant + ondansetron (634 of 1000; RR 0.90, 95% CI 0.79 to 1.03; low certainty), rolapitant + granisetron (627 of 1000; RR 0.89, 95% CI 0.78 to 1.01; moderate certainty), and rolapitant + ondansetron (598 of 1000; RR 0.85, 95% CI 0.65 to 1.12; low certainty). We could not include two treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron) in NMA for this outcome because of missing direct comparisons.  Serious adverse events We estimated that 35 of 1000 participants experience any SAEs when treated with aprepitant + granisetron. Evidence from NMA (23 RCTs, 16,065 participants; 11 treatment combinations) suggests that fewer participants may experience SAEs when treated with the following drug combinations than with aprepitant + granisetron: fosaprepitant + ondansetron (8 of 1000; RR 0.23, 95% CI 0.05 to 1.07; low certainty), casopitant + ondansetron (8 of 1000; RR 0.24, 95% CI 0.04 to 1.39; low certainty), netupitant + palonosetron (9 of 1000; RR 0.27, 95% CI 0.05 to 1.58; low certainty), fosaprepitant + granisetron (13 of 1000; RR 0.37, 95% CI 0.09 to 1.50; low certainty), and rolapitant + granisetron (20 of 1000; RR 0.57, 95% CI 0.19 to 1.70; low certainty). Evidence is very uncertain about the effects of aprepitant + ondansetron (8 of 1000; RR 0.22, 95% CI 0.04 to 1.14; very low certainty), aprepitant + ramosetron (11 of 1000; RR 0.31, 95% CI 0.05 to 1.90; very low certainty), fosaprepitant + palonosetron (12 of 1000; RR 0.35, 95% CI 0.04 to 2.95; very low certainty), fosnetupitant + palonosetron (13 of 1000; RR 0.36, 95% CI 0.06 to 2.16; very low certainty), and aprepitant + palonosetron (17 of 1000; RR 0.48, 95% CI 0.05 to 4.78; very low certainty) on the risk of SAEs when compared to aprepitant + granisetron, respectively.  We could not include three treatment combinations (ezlopitant + granisetron, aprepitant + tropisetron, rolapitant + ondansetron) in NMA for this outcome because of missing direct comparisons.  Moderately emetogenic chemotherapy (MEC) We included 38 studies reporting on 12,038 participants and comparing 15 treatment combinations with NK₁ and 5-HT₃ inhibitors, or 5-HT₃ inhibitors solely. All treatment combinations included corticosteroids. Complete control of vomiting during the overall phase We estimated that 555 of 1000 participants achieve complete control of vomiting in the overall treatment phase (one to five days) when treated with granisetron. Evidence from NMA (22 RCTs, 7800 participants; 11 treatment combinations) suggests that the following drug combinations are more efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days): aprepitant + palonosetron (716 of 1000; RR 1.29, 95% CI 1.00 to 1.66; low certainty), netupitant + palonosetron (694 of 1000; RR 1.25, 95% CI 0.92 to 1.70; low certainty), and rolapitant + granisetron (660 of 1000; RR 1.19, 95% CI 1.06 to 1.33; high certainty).  Palonosetron (588 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) and aprepitant + granisetron (577 of 1000; RR 1.06, 95% CI 0.85 to 1.32; low certainty) may or may not increase complete response in the overall treatment phase (one to five days) when compared to granisetron, respectively. Azasetron (560 of 1000; RR 1.01, 95% CI 0.76 to 1.34; low certainty) may result in little to no difference in complete response in the overall treatment phase (one to five days) when compared to granisetron. Evidence further suggests that the following drug combinations are less efficacious than granisetron in completely controlling vomiting during the overall treatment phase (one to five days) (ordered by decreasing efficacy): fosaprepitant + ondansetron (500 of 100; RR 0.90, 95% CI 0.66 to 1.22; low certainty), aprepitant + ondansetron (477 of 1000; RR 0.86, 95% CI 0.64 to 1.17; low certainty), casopitant + ondansetron (461 of 1000; RR 0.83, 95% CI 0.62 to 1.12; low certainty), and ondansetron (433 of 1000; RR 0.78, 95% CI 0.59 to 1.04; low certainty). We could not include five treatment combinations (fosaprepitant + granisetron, azasetron, dolasetron, ramosetron, tropisetron) in NMA for this outcome because of missing direct comparisons.  Serious adverse events We estimated that 153 of 1000 participants experience any SAEs when treated with granisetron. Evidence from pair-wise comparison (1 RCT, 1344 participants) suggests that more participants may experience SAEs when treated with rolapitant + granisetron (176 of 1000; RR 1.15, 95% CI 0.88 to 1.50; low certainty). NMA was not feasible for this outcome because of missing direct comparisons.  Certainty of evidence Our main reason for downgrading was serious or very serious imprecision (e.g. due to wide 95% CIs crossing or including unity, few events leading to wide 95% CIs, or small information size). Additional reasons for downgrading some comparisons or whole networks were serious study limitations due to high risk of bias or moderate inconsistency within networks., Authors' Conclusions: This field of supportive cancer care is very well researched. However, new drugs or drug combinations are continuously emerging and need to be systematically researched and assessed. For people receiving HEC, synthesised evidence does not suggest one superior treatment for prevention and control of chemotherapy-induced nausea and vomiting.  For people receiving MEC, synthesised evidence does not suggest superiority for treatments including both NK₁ and 5-HT₃ inhibitors when compared to treatments including 5-HT₃ inhibitors only. Rather, the results of our NMA suggest that the choice of 5-HT₃ inhibitor may have an impact on treatment efficacy in preventing CINV.  When interpreting the results of this systematic review, it is important for the reader to understand that NMAs are no substitute for direct head-to-head comparisons, and that results of our NMA do not necessarily rule out differences that could be clinically relevant for some individuals., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Aim:  Probability of survival of patients with vulvar cancer directly depends on the lymph node status. Surgery of lymph nodes can be performed as radical inguinofemoral lymphadenectomy or in cases with certain conditions as sentinel lymph node surgery. The aim of this study is to obtain an overview of the intervention-related morbidity and quality of life in patients with vulvar carcinoma after lymphadenectomy., Methods:  Quality of life and morbidity was compared between patients who underwent radical inguinofemoral lymphadenectomy with those who underwent sentinel lymph node surgery., Results:  All recorded postoperative complications occur more frequently in the non-sentinel group, Significant difference was shown for the occurrence of lymphedema (p-value = 0.024) and sensitivity loss (p-value = 0.024). Recurrence of disease was more frequent in the non-sentinel group (38 % vs. 20 %, p = 0.621, n.s.) and satisfaction with groin surgery is slightly higher in the sentinel group (94 % vs. 89 %, p = 1.000, n.s.)., Conclusion:  We could demonstrate a significantly lower morbidity of sentinel lymphadenectomy compared to conventional inguinofemoral lymphadenectomy while maintaining the same oncological safety. The low morbidity of sentinel- lymphadenectomy does not seem to influence the postoperative quality of life significantly. However, recording of the individual burden of lymphadenectomy by questionnaires should be optimized., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Currently, there is no comprehensive presentation of trends in oral diseases in the German general population over the last 20 years., Objectives: How did prevalences of caries, periodontitis, and tooth loss and their determinants change in Germany between 1997 and 2014?, Materials and Methods: We analysed data from 35- to 44-year-olds and 65- to 74-year-olds from the German Oral Health Studies ("Deutsche Mundgesundheitsstudien" [DMS]) III to V and of 25- to 74-year-olds from the Studies of Health in Pomerania (SHIP‑0 and SHIP-Trend-0). The decayed, missing, filled teeth index (DMFT), the number of sound teeth, the community periodontal index (CPI), and data on tooth count and edentulism were analysed., Results: Regarding determinants, an increase in subjects with high school education, a slight decrease in smokers, and an increase in better oral hygiene patterns was observed in both studies. In 35- to 44-year-olds, the number of sound teeth increased from 11.9 in DMS III to 16.8 in DMS V, while in 65- to 74-year-olds the number of sound teeth increased by 5.9. A similar trend was observed in SHIP. In DMS, the prevalence of the highest CPI score of 4 decreased from 9.3% to 3.5% in 35- to 44-year-olds; in 65- to 74-year-olds, the 2014 prevalence was at the same level as in 1997 (10.5% and 9.8%). In parallel, the percentage of edentulous 65- to 74-year-olds halved in both studies. The number of teeth increased across all age strata., Conclusions: DMS and SHIP consistently showed an increase in the number of healthy teeth free of fillings, a slight reduction of subjects with a CPI score of 4, more tooth retention, and less edentulism. Because of more tooth retention and current demographic changes, higher periodontal treatment needs might be expected for the future.

Background: Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent., Objectives: To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis., Search Methods: We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials., Selection Criteria: We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria., Data Collection and Analysis: Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach., Main Results: Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life., Authors' Conclusions: When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Purpose: Baroreflex activation therapy (BAT) has been shown to lower blood pressure in patients with resistant hypertension. The purpose of this study was to analyze whether this translates into a reduction of more relevant clinical endpoints., Methods: Patients with resistant hypertension were treated with the second-generation BAT system. Records on hospitalization (dates of admission and discharge, main diagnosis) were obtained from medical insurance companies., Results: Records on hospitalization were available for a period of 1 year before BAT in two patients and 2 years in 22 patients. The total number of hospitalizations per patient was 3.3 ± 3.5/year before BAT and 2.2 ± 2.7/year after BAT (p = 0.03). Hospitalizations related to hypertension were significantly decreased from 1.5 ± 1.6/year before BAT to 0.5 ± 0.9/year after BAT (p < 0.01). The cumulative duration of hypertension-related hospital stays was significantly reduced from 8.0 ± 8.7 days/year before BAT to 1.8 ± 4.8 days/year after BAT (p < 0.01). Office cuff blood pressure was 183 ± 27 mmHg over 102 ± 17 mmHg under 6.6 ± 2.0 antihypertensive drugs before BAT and 157 ± 32 mmHg over 91 ± 20 mmHg (both p < 0.01) under 5.9 ± 1.9 antihypertensive drugs (p = 0.09 for number of drugs) at latest follow-up. Daytime ambulatory blood pressure was 164 ± 21 mmHg over 91 ± 14 mmHg before BAT and 153 ± 21 mmHg (p = 0.03) over 89 ± 15 mmHg (p = 0.56) at latest follow-up. Heart rate was 75 ± 16 bpm before BAT and 72 ± 12 bpm at latest follow-up (p = 0.35)., Conclusions: Rate and duration of hypertension-related hospitalizations in patients with severe resistant hypertension were lowered after BAT. Whether the response is mediated through improvements in blood pressure control requires further studies.

Objectives: Systemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (lcSSc, dcSSc and SSc-overlap syndromes)., Methods: Clinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (<40 years, 40-60 years, >60 years)., Results: Among all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age <40 years, and 22.5% were older than 60 years of age. In particular, older patients at onset developed the lcSSc subset significantly more often. Furthermore, they had pulmonary hypertension more often, but digital ulcerations less often. Remarkably, the course of the disease was more rapidly progressing in the older cohort (>60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment., Conclusion: In this large registry, ∼25% of patients developed SSc at an age above 60 years with an increased frequency of lcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Study Design: Prospective cohort study., Objective: We aimed to determine the 2-year survival and to identify clinical and microbiological characteristics of patients with native vertebral osteomyelitis (VO) as compared to postoperative VO to find further strategies for improvement of the management of VO., Summary of Background Data: A relevant subgroup (20%-30%) of patients with VO has a history of spine surgery. Infection in these patients might be clinically different from native VO. However, clinical, microbiological, and outcome characteristics of this disease entity have not been well studied as most trials either excluded these patients or are limited by a small cohort and short observation period., Methods: Between 2008 and 2013, patients who presented at a tertiary care center with symptoms and imaging findings suggestive of VO were reviewed by specialists in infectious diseases, clinical microbiology, and orthopedics to confirm the diagnosis and followed prospectively for a period of 2 years. Statistical analysis for group comparisons, survival analysis, and uni- and multivariable Cox regression models were performed., Results: Thirty percent of the patients with VO (56/189) reported a history of spine surgery in the same segment. Patients with postoperative infection had a lower ASA score (American Society of Anesthesiologists) (P = 0.01) and were less likely to suffer from comorbidities compared to native cases (P = 0.003). Infections caused by coagulase-negative staphylococci (33.3 vs. 6.5%, P < 0.001) and other bacteria of the skin flora (15.2 vs. 0%, P = 0.002) were more prevalent in postoperative patients. Suffering from native VO increased the 2-year mortality risk 3-fold, also when adjusted for the remaining risk factors ASA score and number of comorbidities (hazard ratio 2.916 [95% confidence interval 1.215 -6.999], P = 0.017)., Conclusion: Beside clear microbiological differences, the significant better 2-year survival supports the concept of postoperative VO presenting a distinct disease entity. The subtle disease presentation of patients with postoperative VO should not attenuate clinical suspicion of physicians., Level of Evidence: 3.

Cognitive behavioral therapy for psychosis (CBT) is an effective treatment in adult patients with schizophrenia. However, no randomized controlled and blinded trial in adolescents with early-onset psychosis (EOP) has been conducted. Therefore, the present pilot study explores the acceptance, tolerability, feasibility, and safety of a modified CBT in adolescents with EOP. Twenty-five adolescents with EOP were randomized to either 9 months (20 sessions) of CBT + treatment as usual (TAU) or TAU alone. The primary endpoint was the PANSS-positive subscale (P1-7). Secondary endpoints included psychopathology, global functioning, and quality of life (QoL). Acceptance, tolerability, feasibility, and safety were assessed. Blinded assessments took place by the end of the treatment (9 months) and at 24-month follow-up. Despite improvements in both groups and lack of statistical significance between CBT + TAU and TAU regarding the primary endpoint, we observed between-group effect sizes of at least d = 0.39 in favor of CBT + TAU at post-treatment for delusions, negative symptoms, functioning and QoL after the intervention and effect sizes of at least d = 0.35 after 24 months. CBT in EOP was highly acceptable (73.5% agreed to randomization), well-tolerated (83.1% attendance rate, no drop-outs), and safe (one serious adverse event (SAE) in CBT + TAU in comparison with six SAEs in TAU). These findings suggest that CBT adapted to the needs of adolescents with EOP is a promising approach regarding negative symptoms, functioning, and QoL. CBT is a safe and tolerable treatment. However, due to the small sample size and the pilot character of the study, these conclusions are limited, and should be tested in a larger, adequately powered randomized controlled trial.

Objective: Residual paravalvular regurgitation (PVR) has been associated to adverse outcomes after transcatheter aortic valve replacement (TAVR). This study sought to evaluate the impact of device landing zone (DLZ) calcification on residual PVR after TAVR with different next-generation transcatheter heart valves., Methods: 642 patients underwent TAVR with a SAPIEN 3 (S3; n=292), ACURATE neo (NEO; n=166), Evolut R (ER; n=132) or Lotus (n=52). Extent, location and asymmetry of DLZ calcification were assessed from contrast-enhanced CT imaging and correlated to PVR at discharge., Results: PVR was ≥moderate in 0.7% of S3 patients, 9.6% of NEO patients, 9.8% of ER patients and 0% of Lotus patients (p<0.001), and these differences remained after matching for total DLZ calcium volume. The amount of DLZ calcium was significantly related to the degree of PVR in patients treated with S3 (p=0.045), NEO (p=0.004) and ER (p<0.001), but not in Lotus patients (p=0.698). The incidence of PVR ≥moderate increased significantly over the tertiles of DLZ calcium volume (p=0.046). On multivariable analysis, calcification of the aortic valve cusps, LVOT calcification and the use of self-expanding transcatheter aortic valve implantation (TAVI) prostheses emerged as predictors of PVR., Conclusions: The susceptibility to PVR depending on the amount of calcium was mainly observed in self-expanding TAVI prostheses. Thus, DLZ calcification is an important factor to be considered in prosthesis selection for each individual patient, keeping in mind the trade-off between PVR reduction, risk of new pacemaker implantation and unfavourable valve ha emodynamics., Competing Interests: Competing interests: FD received speakers honoraria from Boston Scientific. NS received travel compensation from Edwards and speakers honoraria and travel compensation from Boston Scientific. VR received speakers honoraria from Medtronic. TCWW and NM are proctors for Edwards. SB is a proctor for Edwards and received a research grant from Edwards. US is proctor for Edwards and Symetis SA and received research grants from Symetis SA and Edwards. TR is proctor for Boston Scientific and and received speakers honoraria from Edwards, Medtronic and Boston Scientific/Symetis., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Scleroderma renal crisis (SRC) is a severe life-threatening manifestation in patients with systemic sclerosis (SSc). However, the knowledge about risk factors for SRC is limited. We determined here the frequency of SRC and identified risk factors for the prediction of SRC., Methods: Based on regular followup data from the German Network for Systemic Scleroderma, we used univariate and multivariate generalized estimating equations to analyze the association between clinical variables, SSc subsets, therapy [i.e., angiotensin-converting enzyme inhibitors (ACEi), corticosteroids], and the occurrence of SRC., Results: Data of 2873 patients with 10,425 visits were available for analysis with a mean number of registry visits of 3.6 ± 2.8 and a mean time of followup of 3.6 ± 3.8 years. In total, 70 patients developed SRC (70/2873, 2.4%). Of these patients, 57.1% (40/70) were diagnosed with diffuse cutaneous SSc, 31.4% (22/70) with limited cutaneous SSc, and 11.4% (8/70) with SSc-overlap syndromes. Predictive independent factors with the highest probability for SRC were positive anti-RNA polymerase antibodies (RNAP), a history of proteinuria prior to SRC onset, diminished DLCO, and a history of hypertension. Interestingly, positive antitopoisomerase autoantibodies did not predict a higher risk for SRC. Further, patients with SRC were significantly more frequently treated with ACEi and corticosteroids without being independently associated with SRC., Conclusion: In this cohort, SRC has become a rare complication. By far the highest risk for SRC was associated with the detection of anti-RNAP and proteinuria.

Background: Multiple myeloma is a bone marrow-based hematological malignancy accounting for approximately two per cent of cancers. First-line treatment for transplant-ineligible individuals consists of multiple drug combinations of bortezomib (V), lenalidomide (R), or thalidomide (T). However, access to these medicines is restricted in many countries worldwide., Objectives: To assess and compare the effectiveness and safety of multiple drug combinations of V, R, and T for adults with newly diagnosed transplant-ineligible multiple myeloma and to inform an application for the inclusion of these medicines into the World Health Organization's (WHO) list of essential medicines., Search Methods: We searched CENTRAL and MEDLINE, conference proceedings and study registries on 14 February 2019 for randomised controlled trials (RCTs) comparing multiple drug combinations of V, R and T for adults with newly diagnosed transplant-ineligible multiple myeloma., Selection Criteria: We included RCTs comparing combination therapies of V, R, and T, plus melphalan and prednisone (MP) or dexamethasone (D) for first-line treatment of adults with transplant-ineligible multiple myeloma. We excluded trials including adults with relapsed or refractory disease, trials comparing drug therapies to other types of therapy and trials including second-generation novel agents., Data Collection and Analysis: Two review authors independently extracted data and assessed risk of bias of included trials. As effect measures we used hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for adverse events. An HR or RR < 1 indicates an advantage for the intervention compared to the main comparator MP. Where available, we extracted quality of life (QoL) data (scores of standardised questionnaires). Results quoted are from network meta-analysis (NMA) unless stated., Main Results: We included 25 studies (148 references) comprising 11,403 participants and 21 treatment regimens. Treatments were differentiated between restricted treatment duration (treatment with a pre-specified amount of cycles) and continuous therapy (treatment administered until disease progression, the person becomes intolerant to the drug, or treatment given for a prolonged period). Continuous therapies are indicated with a "c". Risk of bias was generally high across studies due to the open-label study design. Overall survival (OS) Evidence suggests that treatment with RD (HR 0.63 (95% confidence interval (CI) 0.40 to 0.99), median OS 55.2 months (35.2 to 87.0)); TMP (HR 0.75 (95% CI 0.58 to 0.97), median OS: 46.4 months (35.9 to 60.0)); and VRDc (HR 0.49 (95% CI 0.26 to 0.92), median OS 71.0 months (37.8 to 133.8)) probably increases survival compared to median reported OS of 34.8 months with MP (moderate certainty). Treatment with VMP may result in a large increase in OS, compared to MP (HR 0.70 (95% CI 0.45 to 1.07), median OS 49.7 months (32.5 to 77.3)), low certainty). Progression-free survival (PFS) Treatment withRD (HR 0.65 (95% CI0.44 to 0.96), median PFS: 24.9 months (16.9 to 36.8)); TMP (HR 0.63 (95% CI 0.50 to 0.78), median PFS:25.7 months (20.8 to 32.4)); VMP (HR 0.56 (95% CI 0.35 to 0.90), median PFS: 28.9 months (18.0 to 46.3)); and VRDc (HR 0.34 (95% CI 0.20 to 0.58), median PFS: 47.6 months (27.9 to 81.0)) may result in a large increase in PFS (low certainty) compared to MP (median reported PFS: 16.2 months). Adverse events The risk of polyneuropathies may be lower with RD compared to treatment with MP (RR 0.57 (95% CI 0.16 to 1.99), risk for RD: 0.5% (0.1 to 1.8), mean reported risk for MP: 0.9% (10 of 1074 patients affected), low certainty). However, the CIs are also compatible with no difference or an increase in neuropathies. Treatment with TMP (RR 4.44 (95% CI1.77 to 11.11), risk: 4.0% (1.6 to 10.0)) and VMP (RR 88.22 (95% CI 5.36 to 1451.11), risk: 79.4% (4.8 to 1306.0)) probably results in a large increase in polyneuropathies compared to MP (moderate certainty). No study reported the amount of participants with grade ≥ 3 polyneuropathies for treatment with VRDc. VMP probably increases the proportion of participants with serious adverse events (SAEs) compared to MP (RR 1.28 (95% CI 1.06 to 1.54), risk for VMP: 46.2% (38.3 to 55.6), mean risk for MP: 36.1% (177 of 490 patients affected), moderate certainty). RD, TMP, and VRDc were not connected to MP in the network and the risk of SAEs could not be compared. Treatment with RD (RR 4.18 (95% CI 2.13 to 8.20), NMA-risk: 38.5% (19.6 to 75.4)); and TMP (RR 4.10 (95% CI 2.40 to 7.01), risk: 37.7% (22.1 to 64.5)) results in a large increase of withdrawals from the trial due to adverse events (high certainty) compared to MP (mean reported risk: 9.2% (77 of 837 patients withdrew)). The risk is probably slightly increased with VMP (RR 1.06 (95% CI 0.63 to 1.81), risk: 9.75% (5.8 to 16.7), moderate certainty), while it is much increased with VRDc (RR 8.92 (95% CI 3.82 to 20.84), risk: 82.1% (35.1 to 191.7), high certainty) compared to MP. Quality of life QoL was reported in four studies for seven different treatment regimens (MP, MPc, RD, RMP, RMPc, TMP, TMPc) and was measured with four different tools. Assessment and reporting differed between studies and could not be meta-analysed. However, all studies reported an improvement of QoL after initiation of anti-myeloma treatment for all assessed treatment regimens., Authors' Conclusions: Based on our four pre-selected comparisons of interest, continuous treatment with VRD had the largest survival benefit compared with MP, while RD and TMP also probably considerably increase survival. However, treatment combinations of V, R, and T also substantially increase the incidence of AEs, and lead to a higher risk of treatment discontinuation. Their effectiveness and safety profiles may best be analysed in further randomised head-to-head trials. Further trials should focus on consistent reporting of safety outcomes and should use a standardised instrument to evaluate QoL to ensure comparability of treatment-combinations., (Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm., Methods: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups., Results: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group ( P <0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups., Conclusions: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.

Introduction: The determination of the electrolytes sodium and potassium is essential in critical care. In daily clinical practice, both the blood gas analyzer (ABG) and the laboratory autoanalyzer (AA) are generally applied. However, there is still uncertainty regarding the convergence of the prementioned assays, and data about the comparability dependent on the pH value are still lacking., Materials and Methods: One hundred samples from intensive care unit patients with a range in pH values between 7.20 and 7.49 were evaluated in this retrospective cohort study. All patients suffered an infarct-related cardiogenic shock and were intubated and not under therapeutical hypothermia at the time of blood collection. We used scatter plots to compare different distributions of sodium and potassium values between the methods. Comparability of the analyses was assessed using the Bland-Altmann approach, and intraclass correlations (ICC) as estimates of interrater reliability were calculated., Results: The mean potassium level measured on ABG was 4.33 mmol/L (SD 0.48 mmol/L), and the value obtained using the AA was 4.40 mmol/L (SD 0.55 mmol/L). A Bland-Altman comparison for total potassium measurements revealed that the limits of agreement were small (-0.241 to 0.391 mmol/L). Total ICC displayed a very good correlation of 0.949. For sodium, we found average values of 140 mmol/L (SD 5.20 mmol/L) in the AA and 140 mmol/L (SD 5.80 mmol/L) in the ABG assessment. Contrarily, the Bland-Altman comparison for sodium displayed that the 95% limits of agreement were very wide (-5.99 to 6.59 mmol/L) for total measurements as well as in every pH subgroup. Total ICC only reached a value of 0.830., Conclusion: Data from our single-center study indicate that urgent and vital decisions based on potassium measurements can be made by trusting the value obtained on the ABG machine irrespective of pH values., Competing Interests: The authors declare that they have no conflicts of interest.

Aim: Psychological interventions, such as cognitive behavioural therapy (CBT) and supportive counselling (SC), are used to treat people with schizophrenia and people at clinical high risk (CHR) of psychosis. However, little information is available on predictors of treatment response. This study aims to identify such predictors of psychological interventions in CHR., Methods: A total of 128 help-seeking CHR outpatients were randomized into two groups-integrated psychological intervention (IPI), including CBT, and SC-for 12 months. Multiple regression analysis was used to identify demographic, symptomatic and functional variables that predict improvement in positive (PANSS Positive), negative (PANSS Negative) and basic symptoms (Basic symptom total score) and improvement in functioning (GAF) at 1-year follow up., Results: In the merged group (IPI + SC), people who lived independently, were younger and presented with higher baseline functioning showed more improvement in symptomatic outcomes at follow up. Negative symptoms at baseline predicted less improvement in positive and basic symptoms. Being married or cohabiting and living in the primary family were found to correlate with good functioning at 1-year follow up., Conclusions: Younger CHR individuals and those who are functioning well may particularly benefit from early intervention. Treatment might need to be modified for low-functioning CHR and those who already display higher scores of negative symptoms. Registration number: NCT00204087., (© 2017 John Wiley & Sons Australia, Ltd.)

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed. What is Known: • Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies. • Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. What is New: • This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects. • The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants.

Background: Patients undergoing transcatheter aortic valve replacement (TAVR) are mostly elderly patients with substantial comorbidities. Established risk scores are not validated for TAVR and collectives with elderly patients making periprocedural risk stratification difficult. Serum albumin is known to be an indicator for malnutrition and frailty and is simple to measure, independent of physician's bias. Using serum albumin as a preoperative marker for postoperative complications might help estimating morbidity and mortality of these patients., Methods: A total of 457 patients with severe symptomatic aortic stenosis undergoing TAVR at our institution in a period from January 2014 to December 2015 were included in this retrospective study. Baseline characteristics as well as preoperative laboratory parameters were registered. Postoperative morbidity and 30-day mortality were analyzed as primary end points. Enrolled patients with preoperative low serum albumin (<3.5 g/dL) were compared with those revealing normal serum albumin (≥3.5 g/dL)., Results: Among 457 patients, 51 (11%) presented pre-procedural low serum albumin and 406 (89%) had normal serum albumin. Patients' mean age was 81±6 years and 50% of them were male. Postoperative complications such as requirement of blood transfusions (63% versus 33%, P<0.001), infection (53% versus 24%, P<0.001), acute kidney injury (41% versus 19%, P=0.001) and 30-day mortality (10% versus 3%, P=0.045) showed significant differences between preoperative low and normal albumin groups., Conclusions: Preoperative low serum albumin might be an indicator for higher morbidity and mortality in patients undergoing TAVR., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures., Methods: Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman's rank correlation coefficient rho ( ρ )., Results: Average age of the population was 57.8 ± 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS ( ρ  = - 0.467) and Ramsay Scores ( ρ  = 0.476). Serum concentrations of sufentanil correlated weakly with RASS ( ρ  = - 0.312) and Ramsay Scores ( ρ  = 0.295). Correlations between BIS index and serum concentrations of midazolam ( ρ  = - 0.252) and sufentanil ( ρ  = - 0.166) were low., Conclusion: Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients., Competing Interests: The study protocol was approved by the ethics committee of the University of Cologne (Ref. no. 12-162).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: This study evaluates whether preoperative statin therapy improves clinical outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS)., Methods: A total of 1,151 patients undergoing CABG for ACS were prospectively entered into the North-Rhine-Westphalia surgical myocardial infarction registry and subdivided into two groups according to their preoperative statin status (statin naive vs. statin group). A logistic regression model was employed to analyze the impact of a statin therapy and dose for the endpoints in-hospital mortality and major adverse cardiac events (MACE)., Results: Demographics, pre- and intraoperative data of the statin-naive group ( n  = 208; 18%) and statin-treated group ( n  = 943, 82%) did not differ. In-hospital mortality (12.6 vs. 6.3%, p  = 0.002) and MACE rates (22.1 vs. 9.7%, p  < 0.001) were significantly higher in statin naive when compared with statin-treated patients with ACS, respectively. Mevalonic acid revealed that both low- and high-dose statin treatment was associated to a reduction in in-hospital mortality and MACE, without a dose-dependent statin effect., Conclusion: Statin therapy in patients with ACS undergoing CABG reduces in a dose-independent manner in-hospital mortality and MACE., Competing Interests: None., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Sudden cardiac arrest is still one of the most frequent causes of death. Teaching resuscitation in schools was already successfully implemented in Scandinavian countries. Following a recommendation of the conference of german stateministers of education in June 2014, additional tuition for resuscitation is to be implemented in german schools starting in seventh grade., Methods: The present study aimed to assess the level of knowledge of seventh grade students in the field of life support and to implement curricular standards for resuscitation courses in secondary schools. Using a standardized questionnaire, students in seventh grade of five schools in Cologne were interrogated about their knowledge on resuscitation and defibrillation. This assessment was taken as basis for developing a curricular teaching concept by the Cologne heart centre in cooperation with the department of biology and technical didactics at the University of Cologne. This tutorial concept was integrated in scholar plans for the first time in the school year 2014/2015. At the end of the school year the students' knowledge got reevaluated., Results: As expected, the technical knowledge of the interviewed students is low, however confidence in their own abilities is high. Most of the interviewed persons would be willing to perform chest compressions (72,26%) and dare using an automated external defibrillator (AED, 64,38%). The exact position of defibrillator pads cannot be precisely indicated by most students (8,40%), compression point, -depth and -frequency are known by just one third of students. Already one-time performance of the live-saving lesson resulted in a clear increase of knowledge about resuscitation., Conclusions: The willingness to perform resuscitation measures and confidence in their own abilities are high in seventh grade students. Therefore, the recommendation of the conference of german stateministers of education in June 2014 addresses the right target group. Long-term success of the presented educational concept will be analysed and reported in a longitudinal study.

Aims: This study sought to determine the incidence and identify predictors of acute kidney injury (AKI) following percutaneous edge-to-edge mitral valve repair (PMVR) and compare the risk of AKI between PMVR and surgical mitral valve repair (SMVR)., Methods and Results: We performed a single-centre analysis of 378 patients receiving treatment for mitral regurgitation (196 consecutive patients undergoing PMVR and 182 patients undergoing SMVR). The incidence of AKI (any stage according to KDIGO) following PMVR was 17.9%. Intervention duration (OR 1.01, 95% CI: 1.00-1.02) and peripheral vascular disease (OR 7.69, 95% CI: 3.25-18.17) predicted AKI after PMVR. Patients suffering from AKI after PMVR demonstrated poorer survival (median followup 428 days). SMVR patients were significantly younger, had fewer comorbidities and better renal function at baseline. Nevertheless, AKI occurred numerically more often after SMVR than PMVR (25.8% vs. 17.9%, p=0.060), and a multivariable regression model adjusting for differences between both groups confirmed a significantly lower risk for AKI following PMVR (OR 0.22, 95% CI: 0.11-0.44, p<0.001)., Conclusions: These data show a significant incidence of AKI after PMVR that must be taken into account in periprocedural care. Nevertheless, our data suggest that SMVR carries an even higher risk of AKI, which should be considered when a decision has to be made between the two therapies.

Purpose: Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It may cause a variety of symptoms and is associated with longer hospitalizations and higher mortality. However, to date, only little is known about the extent of hyponatremia in patients with incurable diseases and whether it is associated with physical symptoms in this patient group. This study aims to describe the prevalence of hyponatremia, associated symptoms, and symptom intensity in inpatients with hyponatremia receiving specialist palliative care (SPC)., Methods: This is a retrospective study. Demographic and clinical data as well as symptoms, scored symptom intensity, and laboratory values were collected. All inpatients of a large German University Hospital receiving SPC in 2013 with documented sodium values were included., Results: In 2013, 789 inpatients received SPC of which 710 had documented sodium values. The prevalence of hyponatremia was 38.7% (275/710). A mild degree showed 220 (31,0%), 44 (6.2%) had a moderate, and 11 (1.6%) a severe form. Hyponatremia patients experienced significantly more symptoms than normonatremic patients (mean = 7.71 vs 6.63; p < 0.001). Breathlessness, depressiveness, nausea, vomiting, poor appetite, constipation, and weakness were significantly more frequent in patients with hyponatremia. Furthermore, hyponatremia severity was associated with higher symptom intensity (mean = 13.29 vs 11.28; p < 0.001)., Conclusions: More than one third of all SPC patients showed a hyponatremia, and the hyponatremia grade was associated with symptom burden and symptom intensity. A prospective analysis is needed to further examine this association and the possible influence of hyponatremia correction on symptom burden reduction.

Background: Estimating the quantitative effect of transcatheter mitral valve repair on functional parameters and quality of life is important for individual treatment decision-making., Methods: We combined data from a prospective monocentric cohort study (N = 215) with data from a systematic literature review (PubMed search term "mitraclip", till 30.04.2016) on patients undergoing MitraClip with at least mortality after discharge reported as an outcome. Effects on functional parameters were reported as range of mean change., Results: 36 observational studies and 1 randomized controlled trial were identified. Due to substantial heterogeneity of effect estimates (I 2 -heterogeneity >75%) and inadequate quality of studies with a lack of comparison group in 97.4% and lack of an independent assessment of outcomes in 86.8%, no pooled estimates were calculated. All studies reported improvements of mean New York Heart Association (NYHA) class (0.5-1.9 classes), Short-Form (SF)-12/36 scores (4.4-9.2 for physical component score, 2.6-8.9 for mental component score), 6-min walk distance [(6MWD) 2-336 m] and Minnesota Living with Heart failure questionnaire (MLWHFQ) score (-7 to -18 points), with improvements regarded as clinically relevant in 20 of 29 studies for NYHA class, in all of 7 studies for SF12/36, in 9 of 15 studies for 6MWD and in all of 8 studies for MLWHFQ., Conclusion: MitraClip therapy provides improvements in physical capacity, physical and mental functioning and disease-specific quality of life in the majority of patients. However, more comparative and high-quality studies are required for understanding the heterogeneity of results, which is crucial for optimal patient selection.

Purpose: The aim of the FEELING-ON-ICU study was to compare mortality estimations of critically ill patients based on 'gut feeling' of medical staff and by Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II and Sequential Organ Failure Assessment (SOFA)., Materials and Methods: Medical staff estimated patients' mortality risks via questionnaires. APACHE II, SAPS II and SOFA were calculated retrospectively from records. Estimations were compared with actual in-hospital mortality using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC)., Results: 66 critically ill patients (60.6% male, mean age 63±15years (range 30-86)) were evaluated each by a nurse (n=66, male 32.4%) and a physician (n=66, male 67.6%). 15 (22.7%) patients died on the intensive care unit. AUC was largest for estimations by physicians (AUC 0.814 (95% CI 0.705-0.923)), followed by SOFA (AUC 0.749 (95% CI 0.629-0.868)), SAPS II (AUC 0.723 (95% CI 0.597-0.849)), APACHE II (AUC 0.721 (95% CI 0.595-0.847)) and nursing staff (AUC 0.669 (95% CI 0.529-0.810)) (p<0.05 for all results)., Conclusions: The concept of physicians' 'gut feeling' was comparable to classical objective scores in mortality estimations of critically ill patients. Concerning practicability physicians' evaluations were advantageous to complex score calculation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The management of testicular cancer (TC) requires a complex multimodal therapeutic approach. Despite the availability of regularly updated guidelines, non-guideline-concordant treatment of TC still occurs. The purpose of the present study was to evaluate the compliance patterns in diagnosis and therapy and their potential effects on patient outcomes with respect to the guidelines of the European Association of Urology., Patients and Methods: We performed a retrospective analysis of 131 patients diagnosed with TC who had been referred to our department from September 2015 to October 2016. Patient characteristics were compared with European Association of Urology guideline recommendations., Results: Of the 131 primary treated patients, 23 (18%) had received a non-guideline-concordant treatment. The most common error was undertreatment (n = 12; 52%), mainly due to missing chemotherapy cycles. Overtreatment occurred in 30% of patients (n = 7); however, inappropriate treatment (n = 2; 9%) and misdiagnosis (n = 2; 9%) were rarely observed. In salvage therapy, non-guideline concordant treatment was observed less frequently compared to patients receiving primary therapy (12% vs. 18%). Of the 131 patients, 35 developed a relapse, 23 of whom were treated correctly and 6 of whom were undertreated. Undertreatment of patients resulted in significantly reduced relapse-free survival compared with guideline-concordant management in primary treated patients (P = .005)., Conclusion: Despite the standardization of treatment by interdisciplinary guidelines, its integration into daily practice remains limited. Undertreatment of TC patients is associated with significantly reduced relapse-free survival and should thus be avoided., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Regularly reported patient surveys are an important dimension of hospital quality management. This study investigates whether providing hospital staff with interim feedback on patient survey results following a best practices workshop can help hospitals improve patient centeredness. Standardized surveys with consecutive patient samples were administered in accredited breast cancer center (BCC) hospitals in one German state (18 million inhabitants), over a 6-month period, in 2012. Two studies were conducted by applying a combination of regression point displacement (RPD) and interrupted time series (ITS) designs. In Study 1, 2 of the 27 hospitals that had previously participated in a best practices workshop to discuss patient-centeredness issues were randomly chosen and were provided interim feedback of patient survey results and workshop minutes. In Study 2, 4 randomly chosen hospitals of 32 that had not participated in the workshop also received interim feedback but no workshop minutes. Control hospitals in both studies neither received feedback nor workshop minutes. The impact of interim feedback was evaluated by applying graphical assessments and multiple regression analyses. Both graphical assessments (locally weighted scatterplot smoothing (LOESS) lines, RPD plots) suggested an effect of interim feedback. Multiple regression results did not unambiguously support these findings. The suggested design approach may prove particularly useful to assess effects in pilot studies, when resources are not available to conduct a randomized study or when its conduct is contingent on initial, positive evidence.

Aims: The impact of type of first medical contact (FMC) in the setting of a guideline conform metropolitan ST-elevation myocardial infarction (STEMI) network providing obligatory primary percutaneous coronary intervention (PCI) is unclear., Methods and Results: 3,312 patients were prospectively included between 2006 and 2012 into a registry accompanying the "Cologne Infarction Model" STEMI network, with 68.4% primarily presenting to emergency medical service (EMS), 17.6% to non-PCI-capable hospitals, and 14.0% to PCI-capable hospitals. Median contact-to-balloon time differed significantly by FMC with 89 minutes (IQR 72-115) for EMS, 107 minutes (IQR 85-148) for non-PCI- and 65 minutes (IQR 48-91) for PCI-capable hospitals (p < 0.001). TIMI-flow grade III and in-hospital mortality were 75.7% and 10.4% in EMS, 70.3% and 8.6% in non-PCI capable hospital and 84.4% and 5.6% in PCI-capable hospital presenters, respectively (p both < 0.01). The association of FMC with in-hospital mortality was not significant after adjustment for baseline characteristics, but risk of TIMI-flow grade < III remained significantly increased in patients presenting to non-PCI capable hospitals., Conclusion: Despite differences in treatment delay by type of FMC in-hospital mortality did not differ significantly. The increased risk of TIMI-flow grade < III in patients presenting to non PCI-capable hospitals needs further study.

Aim: Treatment-outcome associations often differ substantially between observational studies (OSs) and randomized controlled trials (RCTs). We investigate causes, focusing on radiotherapy (RT) effects in early breast cancer treatment, to better understand each study type's merits., Methods and Materials: We systematically analyzed three potential causes, by comparing data from a large OS with results from two previously published meta-analyses of RCTs: differences in patient populations combined with heterogeneous treatment effects, non-random treatment decisions in OSs, and differences in therapy administration., Results: RT-survival associations were considerably stronger in our OS than in the RCTs, e.g., a hazard rate for overall survival after breast-conserving therapy of 0.57 in the OS vs 0.90 in the RCTs. The first proposed reason has limited relevance: patient populations differed considerably, but effect heterogeneity between patient groups was limited. The second reason does explain part of the difference: in the OS treatment decisions (being nonrandomized) and prospects differed with patient characteristics. Notably, patients with early recurrences or mortality are generally excluded from RCTs. Their inclusion in OSs leads to stronger treatment-outcome associations., Conclusion: RCTs and OSs each have their own merits. While RCTs have their undisputed benefits, results from OSs that indicate that RT effects in early breast cancer are even stronger than those reported in RCTs should not be ignored.

Conventional lateral spine and hand radiographs are the standard tools to evaluate vertebral morphometry and bone age in children. Beside bone mineral density analyses, dual-energy X-ray absorptiometry (DXA) measurements with lower radiation exposure provide high-resolution scans which are not approved for diagnostic purposes. Data about the comparability of conventional radiographs and DXA in children are missing yet. The purpose of the trial was to evaluate whether conventional hand and spine radiographs can be replaced by DXA scans to diminish radiation exposure. Thirty-eight children with osteogenesis imperfecta or secondary osteoporosis or short stature (male, n=20; age, 5.0-17.0 yr) were included and assessed once by additional DXA (GE iDXA) of the spine or the left hand. Intraclass correlation coefficients (ICCs) were used to express agreement between X-ray and iDXA assessment. Evaluation of the spine morphometry showed reasonable agreement between iDXA and radiography (ICC for fish-shape, 0.75; for wedge-shape, 0.65; and for compression fractures, 0.70). Bone age determination showed excellent agreement between iDXA and radiography (ICC, 0.97). IDXA-scans of the spine in a pediatric population should be used not only to assess bone mineral density but also to evaluate anatomic structures and vertebral morphometry. Therefore, iDXA can replace some radiographs in children with skeletal diseases., (Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to compare approved first-line therapies for patients with multiple myeloma., Methods: A systematic literature search for phase III randomized controlled trials (RCTs) comparing first-line chemotherapies approved in Germany and recommended by guidelines at the time of study design was conducted. Random-effects meta-analysis (MA) was used for direct and the Bucher method for adjusted indirect treatment comparison., Results: One RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for sensitivity analyses. VMP and MPT were superior to MP regarding efficacy endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 0.65-0.75; MPT vs., Mp, Os: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR for non-response 0.92, 0.88-0.95); but had a higher risk of developing any grade 3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 1.43-2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 0.63-1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment comparisons using results of IPD MA yielded similar effect sizes., Conclusions: VMP and MPT seem more effective than MP, VMP was superior to MPT regarding response criteria and AEs. Our results may best be confirmed by a head-to-head trial of VMP vs. MPT.

Objectives: This study sought to evaluate the role of esmolol-induced tight sympathetic control in patients with ST-segment elevation myocardial infarction (STEMI)., Background: Elevated sympathetic drive has a detrimental effect on patients with acute STEMI. The effect of beta-blocker-induced heart rate mediated sympathetic control on myocardial damage is unknown., Methods: The authors conducted a prospective, randomized, single-blind trial involving patients with STEMI and successful percutaneous intervention (Killip class I and II). Patients were randomly allocated to heart rate control with intravenous esmolol for 24 h or placebo. The primary outcome was the maximum change in troponin T release as a prognostic surrogate marker for myocardial damage. A total of 101 patients were enrolled in the study., Results: There was a significant difference between patients allocated to placebo and those who received sympathetic control with esmolol in terms of maximum change in troponin T release: the median serum troponin T concentration increased from 0.2 ng/ml (interquartile range [IQR] 0.1 to 0.7 ng/ml) to 1.3 ng/ml (IQR: 0.6 to 4.7 ng/ml) in the esmolol group and from 0.3 ng/ml (IQR: 0.1 to 1.2 ng/ml) to 3.2 ng/ml (IQR: 1.5 to 5.3 ng/ml) in the placebo group (p = 0.010). The levels of peak creatine kinase (CK), CK subunit MB (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) were lower in the esmolol group compared with placebo (CK 619 U/l [IQR: 250-1,701 U/l] vs. 1,308 U/l [IQR: 610 to 2,324 U/l]; p = 0.013; CKMB: 73.5 U/l [IQR: 30 to 192 U/l] vs. 158.5 U/l [IQR: 74 to 281 U/l]; p = 0.005; NT-proBNP: 1,048 pg/ml (IQR: 623 to 2,062 pg/ml] vs. 1,497 pg/ml [IQR: 739 to 3,318 pg/ml]; p = 0.059). Cardiogenic shock occurred in three patients in the placebo group and in none in the esmolol group., Conclusions: Esmolol treatment statistically significantly decreased troponin T, CK, CK-MB and NT-proBNP release as surrogate markers for myocardial injury in patients with STEMI. (Heart Rate Control After Acute Myocardial Infarction; DRKS00000766)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry., Methods: The data of 3248 patients with SSc were analyzed., Results: Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005., Conclusion: These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

Background: In contemporary practice with early catheterization in most patients with suspected acute myocardial infarction, the clinical utility of new or presumably new left bundle branch block (LBBB) as a diagnostic criterion equivalent to ST-segment elevation is not well established. This study therefore aimed to determine the predictive value of LBBB for the diagnosis of acute transmural myocardial infarction (or ST-segment elevation myocardial infarction, STEMI)., Patients and Methods: Between November 2006 and December 2011, 1,139 consecutive patients presenting to the heart center of the University of Cologne with suspected STEMI were examined. Of these patients, 935 presented with ST elevation, 72 with LBBB, and 132 had neither of these ECG changes. The diagnosis was confirmed with immediate coronary angiography., Results: Compared with ST-segment elevation, LBBB was associated with a higher prevalence of cardiovascular risk factors and end-organ damage, and more patients with LBBB presented with pulmonary edema or cardiogenic shock (Killip III/IV). STEMI was confirmed in 58.3 % of patients with LBBB and in 86.4 % with ST-segment elevation. The sensitivity (0.38 [0.29-0.46]; odds ratio: 1.24) and specificity (0.67 [0.58-0.77]) of LBBB for the prediction of STEMI were low. However, the additional assessment of troponin T (> 0.1 µg/l) increased the predictive value of LBBB significantly. After adjusting for age and gender, no difference in mortality was found between the groups., Conclusion: LBBB with acute chest pain characterizes a cohort of patients with high morbidity and mortality. For the triage of these patients at first contact, additional criteria should be evaluated, which could increase the specificity of LBBB for the diagnosis of STEMI.

Background: Shared decision making (SDM) is considered a gold standard for the cooperation of doctor and patient. SDM improves patients' overall satisfaction and their confidence in decisions that have been taken. The extent to which it might also positively affect patient-relevant, disease-related endpoints is a matter of debate., Methods: We systematically searched the PubMed database and the Cochrane Library for publications on controlled intervention studies of SDM. The quality of the intervention and the risk of bias in each publication were assessed on the basis of pre-defined inclusion and exclusion criteria. The effects of SDM on patient-relevant, disease-related endpoints were compared, and effect sizes were calculated., Results: We identified 22 trials that differed widely regarding the patient populations studied, the types of intervention performed, and the mode of implementation of SDM. In ten articles, 57% of the endpoints that were considered relevant were significantly improved by the SDM intervention compared to the control group. The median effect size (Cohen's d) was 0.53 (0.14-1.49). In 12 trials, outcomes did not differ between the two groups. In all 22 studies identified, 39% of the relevant outcomes were significantly improved compared with the control groups., Conclusion: The trials performed to date to addressing the effect of SDM on patient-relevant, disease-related endpoints are insufficient in both quantity and quality. Although just under half of the trials reviewed here indicated a positive effect, no final conclusion can be drawn. A consensus-based standardization of both SDM-promoting measures and appropriate clinical studies are needed.

Objective: Perioperative complications in patients undergoing transcatheter aortic valve implantation remain a major issue affecting outcome. Because preoperative risk adjustment remains challenging and a valid scoring system is missing, we sought to determine the incidence of peri- and postprocedural complications of transapical (TA) or transaortic (TAO) access to define the influence of specific complications on early safety, 30-day mortality, and 1-year survival. Furthermore, we aimed to develop a risk-stratification model to allow an estimation of the perioperative risk and the 1-year survival rate, based on the individual preoperative condition of each patient., Methods: We performed an outcome analysis of 230 consecutive patients who underwent aortic valve implantation via transapical or transaortic access between 2008 and 2012, with regard to Valve Academic Research Consortium II criteria, including univariate and multivariable regression analysis, to develop a risk-stratification model., Results: Thirty-day mortality was 12.7%. Estimated 1-year survival was 0.69 (95% confidence interval [CI], 0.631-0.757), and 3-year survival was 0.554 (95% CI, 0.474-0.634). Univariate logistic regression analysis revealed a significant influence on 30-day mortality in case of life-threatening bleeding (16.1-fold), abdominal complications (8.5-fold), and acute kidney injury (3.2-fold). Pacemaker implantation (odds ratio, 1.55; 95% CI, 0.42-5.81; P = .512) was not a significant predictor. Concerning use of intraprocedural hemodynamic bridging therapy via cardiopulmonary bypass (CPB), Cox regression analysis revealed no significant survival difference after 1 year. A preoperative risk-stratification model for 1-year survival revealed that a logistic European System for Cardiac Operative Risk Evaluation score >20%, preoperative existing coronary artery disease, and prior myocardial infarction appeared to be significant predictors for diminished survival., Conclusions: Concerning intraprocedural complications, CPB support for hemodynamic stabilization is a safe treatment option. Therefore, the heart team approach with CPB standby represents a life-saving option. Attention should also be drawn to specialized and individual postoperative care, because nonprocedure-specific complications clearly affect postoperative short- and long-term outcome. In addition, the risk-stratification model might facilitate preoperative decision making., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)