[Routine Practice Data for Health Care Analyses: Part 3 of the Manual]. / Versorgungsnahe Daten für Versorgungsanalysen ­ Teil 3 des Manuals.

Analyses of health and health care (hereafter referred to as "health care analyses") usually aim to make transparent the structures, processes, results and interrelationships of health care and to record the degree to which health care systems and their actors have achieved their goals. Health care-related data are an indispensable source of data for many health care analyses. A prerequisite for the examination of a degree of goal achievement is first of all an agreement on those goals that are to be achieved by the system and its substructures, as well as the identification of the determinants of the achievement of the objectives. Primarily it must be examined how safely, effectively and patient-centred systems, facilities and service providers are operating. It also addresses issues of need, accessibility, utilisation, timeliness, appropriateness, patient safety, coordination, continuity, and health economic efficiency and equity of health care. The results of health care include system services (outputs), on the one hand, and results (outcomes), on the other, whereby the results (patient-reported outcomes) and experiences (patient-reported experiences) reported are of particular importance. Health care analyses answer basic questions of health care research: who does what, when, how, why and with which resources and effects in routine health care. Health care analyses thus provide the necessary findings and key figures to further develop health care in order to improve the quality of health care. The applications range from capacity analyses to following innovations up to the concept of regional and supra-regional monitoring of the quality of care given to the population. Given the progress of digitalisation in Health Care, direct data from the care processes will be increasingly available for health care research. This can support care givers significantly if the findings of the studies are applied precisely and correctly within an adequate methodological frame. This can lead to measurable improved health care quality for patients. Data from the process of health care provision have a high potential. Their use needs the same scientific scrutiny as in all other scientific studies.

[Quality assurance and improvement in healthcare: instruments and perspectives]. / Qualität in der Gesundheitsversorgung sichern und weiterentwickeln: Maßnahmen und Perspektiven.

In the German statutory health insurance system, quality healthcare is an imperative - healthcare must correspond to current medical knowledge. The central decision-making body, the Federal Joint Committee (G-BA), uses directives to regulate quality standards and instruments to ensure compliance. The Institute for Quality Assurance and Transparency in Health Care (IQTIG) supports the G­BA in this task with independent scientific recommendations. A central task of the institute is the development of quality indicators based on billing data, patient records, and patient surveys.With regard to instruments for the improvement of quality, the IQTIG distinguishes between improvement instruments, instruments based on selection decisions, and instruments based on incentives for providers. Quality improvement requires quality management and intrinsic motivation on the part of the providers. However, due to perverse incentives, intrinsic motivation and thus quality improvement alone are not always sufficient and must be supplemented by extrinsic incentives and other instruments. In particular, instruments enabling quality-oriented physician and hospital choice have not yet been implemented in Germany. The quality information required to enable patients to make such choices does not yet exist and should be based on billing data and patient surveys. Further, such quality information should be presented as simply and understandably as possible on online comparison platforms.To ensure high-quality healthcare, the various instruments for improving quality must be coordinated with one another and aligned with a system of healthcare targets. Such a system of overarching healthcare targets allows the limited resources to be focused on those areas in which the need for action is greatest.

Rates of Complications After Appendectomy in Children and Adolescents: Pediatric Surgical Compared to General Surgical Hospitals.

BACKGROUND: Appendectomies in children and adolescents are performed in Germany in pediatric surgical (PS) or general surgical hospitals (GS). The aim of this study is to evaluate whether the surgery in a PS or GS hospital has an influence on the postoperative course after appendectomy in children and adolescents. MATERIALS AND METHODS: Nationwide routine data from children and adolescents aged 1-17 y insured by the Local Health Insurance Fund who underwent appendectomy between 2014 and 2016 were analyzed (cohort study). Descriptive statistics were calculated both overall and in the two groups (PS and GS). Patients were additionally examined by age (1-5, 6-12, and 13-17 y), treatment (laparoscopic, open surgical, and conversion), and appendicitis type (nonacute: K36/K37/K38/R10, acute simple: K35.30/K35.8, and acute complex: K35.2/K35.31/K35.32). The influence of surgeon specialization on 90-d secondary surgery and 90-d general complications was assessed by multiple logistic regression. RESULTS: Altogether, 25,065 patients who underwent surgery in 83 PS and 906 GS hospitals were included. Logistic regression analysis revealed that PS was associated with a reduced risk of interventions in the 1-5- and 6-12-y age groups (odds ratio: 0.44, 0.62). Acute complex appendicitis, comorbidities, and open surgery significantly increased the risk for reintervention. PS was associated with an increased risk for complications in the 13-17-y age group (odds ratio: 1.66). CONCLUSIONS: PS and GS hospitals provided safe appendectomies in children and adolescents with low reintervention and complication rates. PS hospitals demonstrated advantages for patients in the 1-5- and 6-12-y age groups and GS hospitals for patients 13-17 y.

Influence of COVID-19 confinement measures on appendectomies in Germany-a claims data analysis of 9797 patients.

PURPOSE: COVID-19 pandemic had multiple influences on the social, industrial, and medical situation in all affected countries. Measures of obligatory medical confinement were suspensions of scheduled non-emergent surgical procedures and outpatients' clinics as well as overall access restrictions to hospitals and medical practices. The aim of this retrospective study was to assess if the obligatory confinement (lockdown) had an effect on the number of appendectomies (during and after the period of lockdown). METHODS: This retrospective study was based on anonymized nationwide administrative claims data of the German Local General Sickness Fund (AOK). Patients admitted for diseases of the appendix (ICD-10: K35-K38) or abdominal and pelvic pain (ICD-10: R10) who underwent an appendectomy (OPS: 5-470) were included. The study period included 6 weeks of German lockdown (16 March-26 April 2020) as well as 6 weeks before (03 February-15 March 2020) and after (27 April-07 June 2020). These periods were compared to the respective one in 2018 and 2019. RESULTS: The overall number of appendectomies was significantly reduced during the lockdown time in 2020 compared to that in 2018 and 2019. This decrease affects only appendectomies due to acute simple (ICD-10: K35.30, K35.8) and non-acute appendicitis (ICD-10: K36-K38, R10). Numbers for appendectomies in acute complex appendicitis remained unchanged. Female patients and in the age group 1-18 years showed the strongest decrease in number of cases. CONCLUSION: The lockdown in Germany resulted in a decreased number of appendectomies. This affected mainly appendectomies in simple acute and non-acute appendicitis, but not complicated acute appendicitis. The study gives no evidence that the confinement measures resulted in a deterioration of medical care for appendicitis.

Current practice of stress ulcer prophylaxis in a surgical patient cohort in a German university hospital.

INTRODUCTION: Stress ulcer prophylaxis (SUP) has been a widespread practice both in intensive care units (ICU) and internal wards at the beginning of the twenty-first century. Clinical data suggests an important overuse of acid suppressive therapy (AST) for this indication. Data on current clinical practice of SUP in surgical patients in a non-ICU setting are spares. In the light of a growing number of reports on serious side effects of AST, this study evaluates the use of AST for SUP in a normal surgical ward in a German university hospital. METHODS: Between January 2016 and June 2016, SUP was analysed retrospectively in 1132 consecutive patients of the Department of Surgery of the Universitätsmedizin Greifswald. RESULTS: The patients managed with and without SUP were similar with respect to demographic data and treatment with anticoagulants, SSRI and glucocorticoids. Patients with SUP were treated more frequently by cyclooxygenase inhibiting drugs (NSAID, COX2-inhibitors), were more frequently treated in the intermediated care unit and had a longer hospital stay. Risk factors for the development of stress ulcers were similarly present in patient groups managed with and without SUP. About 85.7-99.6% of patients were given SUP without an adequate risk for stress ulcer development, depending on the method used for risk assessment. DISCUSSION: Still today, SUP is widely overused in non-ICU surgical patients. Information campaigns on risk factors for stress ulcer development and standard operating procedures for SUP are required to limit potential side effects and increased treatment costs.

[Routine Practice Data for Evaluating Intervention Effects: Part 2 of the Manual]. / Versorgungsnahe Daten zur Evaluation von Interventionseffekten: Teil 2 des Manuals.

The evaluation of intervention effects is an important domain of health services research. The ad hoc commission for the use of routine practice data of the German Network for Health Services Research (DNVF) therefore provides this second part of its manual focusing on the use of routine practice data for the evaluation of intervention effects. First, we discuss definition issues and the importance of contextual factors. Subsequently, general requirements for planning, data collection and analysis as well as concrete examples for the evaluation of intervention effects for the 3 fields of application regarding pharmacotherapy, nonpharmaceutical interventions as well as complex interventions are elaborated. We consider scenarios in which no information from randomized controlled trials (RCTs) comparing the two groups directly is yet available or in which RCTs are already available but an extension of the research question is required. In all examples either with or without randomization, the first and foremost question is always whether the data source is suitable for the specific research question. Most of the examples chosen are from oncology trials, because the necessary data are already available for Germany, at least in some form. Finally, the manual discusses possible challenges for future use of these data.

Early removal of urinary drainage in patients receiving epidural analgesia after colorectal surgery within an ERAS protocol is feasible.

BACKGROUND: ERAS guidelines recommend early removal of urinary drainage after colorectal surgery to reduce the risk of catheter-associated urinary tract infections (CAUTI). Another recommendation is the postoperative use of epidural analgesia (EA). In many types of surgery, EA was shown to increase the risk of postoperative urinary retention (POUR). This study determines the impact of early urinary catheter removal on the incidence of POUR and CAUTI under EA after colorectal surgery. METHODS: Eligible patients were scheduled for colorectal surgery within the local ERAS protocol between April 2015 and September 2016. Urinary drainage was removed on the first postoperative day while EA was still in place (early removal group (ER)). The incidences of POUR and CAUTIs were recorded prospectively. Results were compared with a historical control (CG), which was operated between October 2013 and March 2015. RESULTS: POUR occurred significantly more often in the ER (ER 7.8%; CG 2.6%), while CAUTIs were significantly less frequent in the ER (13.8%) compared with the CG (30.4%). Patients who developed POUR were characterised by a significantly higher rate of abdominoperineal resections, by a higher frequency of rectal cancer, and a higher male-to-female ratio compared with patients who did not develop POUR. CONCLUSION: Early removal of urinary drainage after colorectal surgery while EA is still in place is feasible; it reduces the incidence of CAUTI but increases the risk of POUR. Thus, screening for POUR in patients with failure to void after six to 8 h is mandatory under these clinical conditions.

Laparoscopic versus open gastrectomy for locally advanced gastric cancer: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: This meta-analysis sought to evaluate the potential benefits and harms of laparoscopic gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer versus open surgery. METHODS: A comprehensive search for randomized controlled studies that compared laparoscopic versus open gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer published until December 31, 2018, was conducted. Operative outcomes, early postoperative outcomes, and long-term results were analyzed using a random effects model. RESULTS: Five randomized controlled trials containing a collective total of 2157 patients were included. In comparison with open surgery, laparoscopic gastrectomy for locally advanced gastric cancer showed similar risks of short-term mortality and serious adverse events within 30 days after surgery. Regarding intraoperative outcomes, operative time was increased for the laparoscopic approach, whereas the estimated intraoperative blood loss tended to be less. However, the amount of evidence was low for most outcomes. In addition, the results for the length of hospital stay and time to first flatus did not show statistically significant differences. The number of harvested lymph nodes and compliance with D2 lymphadenectomy did not significantly differ between the two groups, indicating oncological equivalence of both approaches. However, long-term oncological results could not be evaluated due to a lack of relevant data in four of the trials. CONCLUSION: Laparoscopic gastrectomy with D2 lymphadenectomy can be performed with equivalent overall short-term morbidity and mortality versus the open approach for locally advanced gastric cancer. However, further well-designed randomized controlled trials are necessary to assess the possible advantages and risks of the laparoscopic approach as well as the long-term results.

Extensively drug-resistant Klebsiella pneumoniae ST307 outbreak, north-eastern Germany, June to October 2019.

From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.

[Quality Assurance Using Administrative/Routine Data for Cholelithiasis - Changes Over Time and Current Status]. / Qualitätssicherung mit Routinedaten bei Cholelithiasis ­ Veränderungen und aktueller Stand.

Quality assurance using administrative/routine data (QSR) is a relatively new measure to assess outcome quality. This approach is methodologically distinct from external quality assurance, as well as from quality assurance based upon registries. Since 2011, QSR for cholelithiasis within AOK patients has been overseen by the Scientific Institute of the AOK (WIdO). Following the introduction of an expert panel in 2013, numerous changes were put into place, whereby the indicator rates for transfusion/bleeding, various complications as well as the overall indicator were reduced. Interestingly, the risk adjusted quality differences between hospitals remained solid.

Metabolic biomarker signature to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis.

OBJECTIVE: Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose. DESIGN: For a case-control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies. Metabolomic profiles of plasma and serum samples were generated from 477 metabolites identified by gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: A biomarker signature (nine metabolites and additionally CA19-9) was identified for the differential diagnosis between PDAC and CP. The biomarker signature distinguished PDAC from CP in the training set with an area under the curve (AUC) of 0.96 (95% CI 0.93-0.98). The biomarker signature cut-off of 0.384 at 85% fixed specificity showed a sensitivity of 94.9% (95% CI 87.0%-97.0%). In the test set, an AUC of 0.94 (95% CI 0.91-0.97) and, using the same cut-off, a sensitivity of 89.9% (95% CI 81.0%-95.5%) and a specificity of 91.3% (95% CI 82.8%-96.4%) were achieved, successfully validating the biomarker signature. CONCLUSIONS: In patients with CP with an increased risk for pancreatic cancer (cumulative incidence 1.95%), the performance of this biomarker signature results in a negative predictive value of 99.9% (95% CI 99.7%-99.9%) (training set) and 99.8% (95% CI 99.6%-99.9%) (test set). In one third of our patients, the clinical use of this biomarker signature would have improved diagnosis and treatment stratification in comparison to CA19-9.

Partial pancreatoduodenectomy versus duodenum-preserving pancreatic head resection in chronic pancreatitis: the multicentre, randomised, controlled, double-blind ChroPac trial.

BACKGROUND: There is substantial uncertainty regarding the optimal surgical treatment for chronic pancreatitis. Short-term outcomes have been found to be better after duodenum-preserving pancreatic head resection (DPPHR) than after partial pancreatoduodenectomy. Therefore, we designed the multicentre ChroPac trial to investigate the long-term outcomes of patients with chronic pancreatitis within 24 months after surgery. METHODS: This randomised, controlled, double-blind, parallel-group, superiority trial was done in 18 hospitals across Europe. Patients with chronic pancreatitis who were planned for elective surgical treatment were randomly assigned to DPPHR or partial pancreatoduodenectomy with a central web-based randomisation tool. The primary endpoint was mean quality of life within 24 months after surgery, measured with the physical functioning scale of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Primary analysis included all patients who underwent one of the assigned procedures; safety analysis included all patients who underwent surgical intervention (categorised into groups as treated). Patients and outcome assessors were masked to group assignment. The trial was registered, ISRCTN38973832. Recruitment was completed on Sept 3, 2013. FINDINGS: Between Sept 10, 2009, and Sept 3, 2013, 250 patients were randomly assigned to DPPHR (n=125) or partial pancreatoduodenectomy (n=125), of whom 226 patients (115 in the DPPHR group and 111 in the partial pancreatoduodenectomy group) were analysed. No difference in quality of life was seen between the groups within 24 months after surgery (75·3 [SD 16·4] for partial pancreatoduodenectomy vs 73·0 [16·4] for DPPHR; mean difference -2·3, 95% CI -6·6 to 2·0; p=0·284). The incidence and severity of serious adverse events did not differ between the groups. 70 (64%) of 109 patients in the DPPHR group and 61 (52%) of 117 patients in the partial pancreatoduodenectomy group had at least one serious adverse event, with the most common being reoperations (for reasons other than chronic pancreatitis), gastrointestinal problems, and other surgical morbidity. INTERPRETATION: No differences in quality of life after surgery for chronic pancreatitis were seen between the interventions. Results from single-centre trials showing superiority for DPPHR were not confirmed in the multicentre setting. FUNDING: German Research Foundation (DFG).

The MRI Sepsis Score: An Innovative Tool for the Evaluation of Septic Peritonitis in Mice Using 7-Tesla Small Animal MRI.

BACKGROUND: Magnetic resonance imaging (MRI) techniques are rarely used in the context of abdominal sepsis and in sepsis research. This study investigates the impact of MRI for monitoring septic peritonitis in an animal model (colon ascendens stent-induced peritonitis, CASP). The CASP model closely mimics that of human disease and is highly standardized. The most frequently employed readout parameter in mouse CASP studies is prolonged or decreased rate of survival. Monitoring the progression of peritonitis via MRI could provide a helpful tool in the evaluation of severity. The use of alternative readout systems could very well reduce the number of research animals. Perspectively, clinical improvement after certain treatment could be classified. METHODS: This study describes for the first time MRI findings following the induction of septic peritonitis in mice using the CASP model. Two sublethal groups of mice with septic peritonitis were investigated. Each had received one of two differing stent diameters in order to control the leakage of feces into the abdominal cavity. Each mouse served as its own control. Imaging and analyses were performed blinded. Gut diameters, stomach volume, abdominal organ wall diameters, and volume of the adrenal glands were measured. Serum corticosterone levels were detected using ELISA. Serum IL-6, TNF-α, IL-1ß, and IL-10 levels were screened by cytometric bead array. Statistical analysis was performed using the Mann-Whitney U test for nonparametric probes and the Kruskal-Wallis and t tests. RESULTS: Using a 7-tesla MRI scanner 24 and 48 h after induction of septic peritonitis, interenteric fluid, organ swelling of spleen and adrenal glands, as well as dilatation of the stomach were compared to nonseptic conditions. Swelling of adrenal glands resulted in an increased serum corticosterone level. In addition, the wall of the intestine bowel was thickened. Based upon these findings, an MRI score (MRI sepsis score, MSS) for abdominal sepsis in mice was established. Reduced stent sizes led to reduced severity of the abdominal sepsis, which could be reproduced in the MSS, which is described here for the first time. CONCLUSIONS: Intraabdominal variations during septic peritonitis are detectable by MRI techniques. MRI methods should become a more important tool for the evaluation of abdominal peritonitis. MSS could provide an interesting tool for the evaluation of therapeutic strategies.

S1P Signalling Differentially Affects Migration of Peritoneal B Cell Populations In Vitro and Influences the Production of Intestinal IgA In Vivo.

Introduction: Sphingosine-1-phosphate (S1P) regulates the migration of follicular B cells (B2 cells) and directs the positioning of Marginal zone B cells (MZ B cells) within the spleen. The function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed in peritoneal B cells by real-time polymerase chain reaction (qPCR). The chemotactic response to S1P was studied in vitro. The role of S1P signalling was further explored in a s1p4-/- mouse strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4 (S1P1 and S1P4, respectively). S1P1 showed differential expression between the distinct peritoneal B cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration response to S1P. s1p4-/- mice displayed significant alterations in the composition of peritoneal B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA) in the gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P4 deficiency alters the composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.

Chronic stress increases experimental pancreatic cancer growth, reduces survival and can be antagonised by beta-adrenergic receptor blockade.

BACKGROUND/OBJECTIVES: Chronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer. METHODS AND RESULTS: Tumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011 < p < 0.043). Also, tumours of stressed mice showed a tendency towards fewer total CD4 cells, more regulatory T cells (Treg), less T cell/tumour cell contacts and a reduction of CTLA-4 in CD4 cells (p > 0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p < 0.012) and in vivo employing chronic stress (p < 0.001). After 5 weeks tumour volumes were 130% (p = 0.0061) larger and median survival reduced by 13.5% (p = 0.0058). Tumours expressed more VEGF (p = 0.0334), had greater microvessel densities (p = 0.047), and an increased MMP-9 expression (p = 0.0456). Beta-catecholamines increased proliferation in tumour cells by 18% (p < 0.0001) and migration by 78% (p = 0.0348) whereas the beta-blocker propranolol reduced these effects by 25% (p < 0.0001) and 53% (p = 0.045), respectively. When stressed tumour-bearing animals were treated with propranolol tumour volumes were reduced by 69% (p = 0.0088) and survival improved by 14% (p < 0.0058). CONCLUSIONS: The potential treatment with beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials.

Surgical trauma leads to a shorter survival in a murine orthotopic pancreatic cancer model.

BACKGROUND: Abdominal surgery is frequently followed by immune dysfunction usually lasting for several days. This is especially important in cases with tumour diseases as an intact immune function is essential in this situation. Therefore, we analysed the outcome of tumour-bearing mice in a mouse model of surgically induced immune dysfunction (SID). METHODS: In male C57BL/6 mice, a pancreatic tumour was implanted orthotopically. Following tumour implantation, the model of SID was applied. The control groups were either laparotomised or underwent no surgical procedure. The survival rate was determined by observation for >60 days. The tumour growth progress was imaged by a 7-tesla small animal MRI. RESULTS: On day 60 after tumour implantation, the survival rate in SID mice was reduced to 41%. In the laparotomised group, 81% of mice survived, while the control group had a survival rate of 75%. These differences were significant (SID vs. control: p < 0.02, and SID vs. laparotomy: p < 0.002). The tumour volume was not influenced by the degree of surgical trauma. CONCLUSION: In pancreatic cancer, the SID model is ideally suited to investigate the influence of SID on this tumour entity.