Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.

[Interprofessional recommendations on behalf of Société française de radiothérapie oncologique for the prevention, protection and management of cyberattacks in radiation oncology]. / Prévention, protection, et gestion des cyberattaques en oncologie radiothérapie : recommandations interprofessionnelles au nom de la Société française de radiothérapie oncologique.

Cybersecurity is currently a major issue. Large hospitals are no longer the only main targets of attacks, but all healthcare organizations and establishments, without distinction of size or activities. The information system is defined as all the resources needed to collect images, store and process them with general distribution of multiple information within an organization. Systems are therefore crucial for the functioning of a medical department. Radiation oncology is one of the specialties most dependent on digital resources, for imaging, data transfer, dosimetry, treatment and so on.. Radiation oncology departments are therefore a prime target for ransomware attacks, which have increased significantly in recent years. Cybersecurity can be likened to a viral or bacterial attack. It is based on the two usual pillars of antimicrobial protection : hygiene and prophylaxis. In this article, we will detail by analogy the three classic levels of prevention of a bacillary attack: "primary prevention", which acts upstream of the infection; "secondary prevention", which acts at an early stage of its evolution; and "tertiary prevention", which acts on complications and risks of recurrence. This article is the result of an interprofessional group on behalf of SFRO, the French society of radiation oncology, with the aim of helping all teams to implement safety adapted to the specificities of a radiation oncology department in France.

Emergency care nurses' self-reported clinical competence before and after postgraduate education - a cross-sectional study.

Changing prerequisites in healthcare leads to the increased complexity of nursing. Since there are no regulations on re-validation of competencies for emergency nurses in Sweden there is sparse knowledge on how nurses develop competencies after registration as nurses (RN). AIM: To describe self-reported professional competence after postgraduate education among RNs in emergency care settings. METHOD: A cross-sectional design and STROBE guidelines were used. The short version of the Nurse Professional Competence Scale was used for data collection and the data were collected before and after postgraduate education, descriptive and comparative statistic was used for analysis. RESULTS: 62 (71%) students participated in the first data collection and an independent group of 31 (48%) students participated in the second data collection. The results showed generally good competencies before entering education and significantly improved competencies after education were found in areas of working independently and reviewing literature for evidence-based nursing Conclusion: The competencies were assessed as very good after education. Evaluating nurses' competencies supports educators in developing education to ensure the need for knowledge in emergency care. To ensure required competencies among emergency care nurses there is a need to regulate additional training and re-validation of emergency nurses' competencies.

Maternal mental health and adverse birth outcomes.

Recent research in economics emphasizes the role of in utero conditions for the health endowment at birth and in early childhood and for social as well as economic outcomes in later life. This paper analyzes the relation between maternal mental health during pregnancy and birth outcomes of the child. In particular, we analyze the relationship between maternal mental health during pregnancy and the probability of giving birth preterm (PT), having a newborn at low birth weight (LBW) or being small for gestational age (SGA). Based on large population-representative data from the German Socio-Economic Panel (SOEP) and cohort data from the National Educational Panel Study (NEPS), we present extensive descriptive evidence on the relationship between maternal mental health and preterm birth by carrying out OLS estimates controlling for a wide range of socioeconomic characteristics. In addition, we apply matching estimators and mother fixed effects models, which bring us closer toward a causal interpretation of estimates. In summary, the results uniformly provide evidence that poor maternal mental health is a risk factor for preterm birth and low birth weight in offspring. In contrast, we find no evidence for an relationship between maternal mental health and small for gestational age at birth.

Successful treatment of severe quetiapine intoxication with CytoSorb hemoadsorption.

WHAT IS KNOWN AND OBJECTIVE: While many drug poisonings are successfully treated with specific antidotes, intoxications with tricyclic antidepressants and/or atypical neuroleptics still represent a major challenge. Besides conventional approaches, a new hemoadsorption device might represent an opportunity for therapeutic detoxification. CASE SUMMARY: We report a 64-year-old female patient who attempted suicide by ingesting an unknown dose of quetiapine. Following application of all available standard diagnostic and therapeutic measures, she was admitted to the intensive care in a deeply somnolent state. Gastroscopy was performed necessitating analgo-sedation, intubation, and mechanical ventilation. Since quetiapine is in principle not dialysable, CytoSorb hemoadsorption was commenced resulting in a clear and rapid decrease in plasma levels of quetiapine and its metabolite norquetiapine over the next few hours. The next day, analgesia was stopped, the patient became alert, and cooperative so that she could be extubated without issues. CytoSorb blood purification therapy was discontinued after 2 days. One day later, the patient was transferred to a psychiatric clinic. WHAT IS NEW AND CONCLUSION: We were able to quickly and efficiently reduce quetiapine and norquetiapine to non-toxic serum levels and to stabilize a critical situation using CytoSorb. Therefore, in the absence of a proven beneficial treatment regimen, the use of CytoSorb might represent an alternative for life-threatening complications of quetiapine intoxication. In particular, intoxications caused by lipophilic agents should be further evaluated.

Validation study of German inpatient administrative health data for epidemiological surveillance and measurement of quality of care for sepsis: the OPTIMISE study protocol.

INTRODUCTION: Sepsis is a major cause of preventable deaths in hospitals. This study aims to investigate if sepsis incidence and quality of care can be assessed using inpatient administrative health data (IAHD). METHODS AND ANALYSIS: Design: Retrospective observational validation study using routine data to assess the diagnostic accuracy of sepsis coding in IAHD regarding sepsis diagnosis based on medical record review. PROCEDURE: A stratified sample of 10 000 patients with an age ≥15 years treated in between 2015 and 2017 in 10 German hospitals is investigated. All available information of medical records is screened by trained physicians to identify true sepsis cases ('gold standard') both according to current ('sepsis-1') definitions and new ('sepsis-3') definitions. Data from medical records are linked to IAHD on patient level using a pseudonym. ANALYSES: Proportions of cases with sepsis according to sepsis-1 and sepsis-3 definitions are calculated and compared with estimates from coding of sepsis in IAHD. Predictive accuracy (sensitivity, specificity) of different coding abstraction strategies regarding the gold standard is estimated. Predictive accuracy of mortality risk factors obtained from IAHD regarding the respective risk factors obtained from medical records is calculated. An IAHD-based risk model for hospital mortality is compared with a record-based risk model regarding model-fit and predicted risk of death. Analyses adjust for sampling weights. The obtained estimates of sensitivity and specificity for sepsis coding in IAHD are used to estimate adjusted incidence proportions of sepsis based on German national IAHD. ETHICS AND DISSEMINATION: The study has been approved by the ethics commission of the Jena University Hospital (No. 2018-1065-Daten). The results of the study will be discussed in an expert panel to write a memorandum on improving the utility of IAHD for epidemiological surveillance and quality management of sepsis care. TRIAL REGISTRATION NUMBER: DRKS00017775; Pre-results.

Bisphenol A in dental materials - existence, leakage and biological effects.

OBJECTIVE: Recently, questions have been raised concerning the potential endocrine disrupting effects of bisphenol A (BPA). This substance is a constituent in many different products which we frequently come into contact with, such as food containers and receipts. Resin-based dental filling materials are another source of exposure, although according to previous studies the amount and potential risks are not clear. Thus, the aims of the present study were (1) to identify if direct dental filling materials are liable to leak BPA and (2) to investigate if this leakage could lead to any adverse effects on health. MATERIALS AND METHODS: A literature search was made with PubMed as the primary source, subsequently complemented with reference tracking. RESULTS: A total of 26 articles were included, 24 of which were used for the first aim (leakage) and 2 for the second aim (health risks). The majority of studies, including all in vivo studies, showed leakage of BPA from dental materials in various amounts and during different time intervals. The findings showed a contradiction in results regarding the connection between dental materials and adverse health effects. CONCLUSIONS: There is leakage of BPA from some dental materials, but critical levels are not evident. Bis-DMA contents might convert to BPA in the oral cavity. There is a contradiction between in vitro and in vivo studies concerning BPA leakage and finally, there is a lack of studies investigating the association between BPA exposure and its adverse effects on human health.

Barriers in achieving patient participation in the critical care unit.

OBJECTIVES: Patient participation in healthcare is important for optimizing treatment outcomes and for ensuring satisfaction with care. Therefore, this study aims to identify barriers to patient participation in the critical care unit, as identified by critical care nurses. DESIGN AND SETTINGS: Qualitative data were collected in four focus group interviews with 17 nurses from two separate hospitals. The interviews were analyzed using qualitative content analysis. FINDINGS: The results show three main categories: nurse's attitude toward caring, the organization of the critical care unit and the patient's health condition. CONCLUSION: Barriers for patient participation in the ICU were found and this lead to a power imbalance between patient and nurse. In contrast to other care settings, this imbalance could be a consequence of the critical care organization and its degree of highly specialized care. The clinical application of our results is that these barriers should be considered when implementing patient participation in such a highly technological care situation as a critical care unit.

Prostate-specific antigen bounce in patients treated before 60 years old by iodine 125 brachytherapy for prostate cancer is frequent and not a prognostic factor.

PURPOSE: The only prognostic factor of prostate-specific antigen (PSA) bounce in prostate cancer found in several studies is young age but has never been specifically studied in this subset of patients for long-term results. Bounce characteristics, histological, clinical, and dosimetric data in young patients were analyzed, as well as their impact on toxicity and survival. MATERIAL AND METHODS: This retrospective study included patients aged ≤60 years treated with exclusive iodine 125 brachytherapy with low or intermediary prostate adenocarcinoma during 1999-2014. Exclusion criteria were a follow-up of ≤24 months. PSA bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below. RESULTS: This study analyzed 179 patients. Median age was 56 years (46-59 years). The median follow-up was 79 months (54; 123). The bounce incidence was 56.8% (49.6%; 64.2%) at 5 years, inversely proportional to positive/total biopsies ratio (HR 0.98, 95% CI [0.97, 0.99]). Incidence of biochemical failure was 1.2%, 95% CI (0.3%; 4.7%), at 5 years with no difference between the bounce and no-bounce group (HR 0.96, 95% CI [0.25; 3.58]). Bounce is an unfavorable prognostic factor for grade two and three urinary toxicities 6.67 (4.14; 10.76) (p < 0.001). CONCLUSIONS: PSA bounce is common in young people after brachytherapy. It should be monitored without starting an inadequate and sometimes invasive relapse checkup or a relapse treatment.

Molecular signatures of liver dysfunction are distinct in fungal and bacterial infections in mice.

Rationale: The liver is a central organ not only for metabolism but also immune function. Life-threatening infections of both bacterial and fungal origin can affect liver function but it is yet unknown whether molecular changes differ depending on the pathogen. We aimed to determine whether the hepatic host response to bacterial and fungal infections differs in terms of hepatic metabolism and liver function. Methods: We compared murine models of infection, including bacterial peritoneal contamination and infection (PCI), intraperitoneal and systemic C. albicans infection, at 6 and 24 h post-infection, to sham controls. The molecular hepatic host response was investigated by the detection of regulatory modules based on large-scale protein-protein interaction networks and expression data. Topological analysis of these regulatory modules was used to reveal infection-specific biological processes and molecular mechanisms. Intravital microscopy and immunofluorescence microscopy were used to further analyze specific aspects of pathophysiology such as cholestasis. Results: Down-regulation of lipid catabolism and bile acid synthesis was observed after 6 h in all infection groups. Alterations in lipid catabolism were characterized by accumulation of long chain acylcarnitines and defective beta-oxidation, which affected metabolism by 6 h. While PCI led to an accumulation of unconjugated bile acids (BA), C. albicans infection caused accumulation of conjugated BA independent of the route of infection. Hepatic dye clearance and transporter expression revealed reduced hepatic uptake in fungal infections vs. defects in secretion following polybacterial infection. Conclusion: Molecular phenotypes of lipid accumulation and cholestasis allow differentiation between pathogens as well as routes of infection at early stages in mice. Targeted metabolomics could be a useful tool for the profiling of infected/septic patients and the type of pathogen, with subsequent customization and targeting of therapy.

Molecular characterization of PRM-associated endometrial changes, PAEC, following mifepristone treatment.

OBJECTIVE: The progesterone receptor modulator (PRM) mifepristone holds the potential to be developed for regular contraception. However, long-term treatment can cause thickening of the endometrium and PRM-associated endometrial changes (PAEC). The objective of this study was to explore the molecular expression of endometrium displaying PAEC after mifepristone treatment in order to understand the future implications of PAEC and safety of long-term use. STUDY DESIGN: Endometrial biopsies were obtained from premenopausal women following 3 months of continuous mifepristone treatment. The biopsies were evaluated regarding occurrence of PAEC and followed up by a comparative analysis of gene expression in PAEC endometrium (n=7) with endometrium not displaying PAEC (n=4). Methods used included microarray analysis, Ingenuity Pathway Analysis (IPA) and real-time polymerase chain reaction. RESULTS: Three genes relevant within endometrial function were up-regulated with PAEC: THY1 (p=.02), ADAM12 (p=.04) and TN-C (p=.04). The proliferation marker MKi67 was not altered (p=.31). None of the differentially regulated genes were involved in the endometrial cancer-signaling pathway (based on IPA knowledge database). CONCLUSION: The genes altered in endometrium displaying PAEC after 3 months of mifepristone exposure are mainly involved in the structural architecture of tissue. IMPLICATIONS: PAEC features may be explained by the altered genes and their networks affecting tissue architecture although not involved in endometrial cancer signaling pathways, and thus, treatment with mifepristone at this dosage does not show any adverse effect at endometrial level.

[Case Report - Metamizole-Induced Agranulocytosis]. / Kasuistik: Metamizol-induzierte Agranulozytose.

Metamizole is primarily used for severe perioperative pain, acute injury and colic, and cancer pain. For other acute/chronic forms of pain and high fever, it should only be used if unresponsive to other agents. Metamizole should not be used for middle and low pain. Oral application should be preferred. A contraindication for metamizole is leukopenia. Clinical signs for agranulocytosis are fever, tonsillitis and aphthous stomatitis.

An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis.

Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease. In the absence of relevant animal models and patient brain specimens, we took advantage of induced pluripotent stem cell (iPSC) technology to model the disease. We established human iPSCs from two males with mutated DCX and classical lissencephaly including smooth brain and abnormal cortical morphology. The disease was recapitulated by differentiation of iPSC into neural cells followed by expression profiling and dissection of DCX-associated functions. Here we show that neural stem cells, with absent or reduced DCX protein expression, exhibit impaired migration, delayed differentiation and deficient neurite formation. Hence, the patient-derived iPSCs and neural stem cells provide a system to further unravel the functions of DCX in normal development and disease.

Pain after tonsillectomy: effectiveness of current guidelines?

BACKGROUND: Tonsillectomy is one of the most common major surgical procedures performed in children. In 2013, the use of codeine in children was severely restricted. French guidelines for treating tonsillectomy's postoperative pain at home have been reconsidered OBJECTIVE: The aim of our study was to measure effectiveness and safety of two schedules: acetaminophen + ibuprofen (A + I) and acetaminophen + tramadol (A + T) in children who underwent tonsillectomy. SETTING AND PATIENTS: We undertook a 1 year prospective and observational single-center study. All children who underwent tonsillectomy were eligible. The choice of the regimen, A + I group or A + T group, was left for the anesthesiologist in charge, done during the pre-anesthetic assessment. After hospital discharge, parents had to give systematically A + I or A + T, 4 times a day during 5 days and then acetaminophen alone for the next 5 days The primary endpoint was the home pain assessed using Parents' Postoperative Pain Measurement Short Form (PPPM-SF) scale. Secondary endpoints were the rate of further hospitalization and/or surgery due to tonsillectomy-related adverse events. RESULTS: Over the study period, 342 tonsillectomies were performed. The return rate of PPPM-SF scales was 58%. Two hundred patients were analyzed. The median age was 4 [3; 5.2] years and was lower in group A + I (4 [3; 5]; 5 [4; 7]; p < 0.0001). PPPM-SF scores were greater than or equal to 3 in both groups during the first 6 postoperative days. The mean decrease of PPPM-SF score over time was higher in group A + I than in group A + T (p = 0.007). Readmission rate was significantly higher in group A + T (A + I: 0; A + T: 7; p = 0.002) as the rate of reoperation for bleeding (A + I: 0; A + T: 3; p = 0.049). CONCLUSION: Home pain management after tonsillectomy should be improved. In clinical practice, A + I seems at least as effective as the combination A + T, without increasing readmission and/or additional surgery for bleeding.

Acid Sphingomyelinase Inhibition Prevents Development of Sepsis Sequelae in the Murine Liver.

The molecular mechanisms of maladaptive response in liver tissue with respect to the acute and post-acute phase of sepsis are not yet fully understood. Long-term sepsis survivors might develop hepatocellular/hepatobiliary injury and fibrosis. Here, we demonstrate that acid sphingomyelinase, an important regulator of hepatocyte apoptosis and hepatic stellate cell (HSC) activation, is linked to the promotion of liver dysfunction in the acute phase of sepsis as well as to fibrogenesis in the long-term. In both phases, we observed a beneficial effect of partial genetic sphingomyelinase deficiency in heterozygous animals (smpd1+/-) on oxidative stress levels, hepatobiliary function, macrophage infiltration and on HSC activation. Strikingly, similar to heterozygote expression of SMPD1, either preventative (p-smpd1+/+) or therapeutic (t-smpd1+/+) pharmacological treatment strategies with desipramine - a functional inhibitor of acid sphingomyelinase (FIASMA) - significantly improved liver function and survival. The inhibition of sphingomyelinase exhibited a protective effect on liver function in the acute-phase, and the reduction of HSC activation diminished development of sepsis-associated liver fibrosis in the post-acute phase of sepsis. In summary, targeting sphingomyelinase with FDA-approved drugs is a novel promising strategy to overcome sepsis-induced liver dysfunction.

Early detection and integrated care for adolescents and young adults with psychotic disorders: the ACCESS III study.

OBJECTIVE: The objective of the study was to investigate whether a combined intervention composed of early detection plus integrated care (EDIC) enhances outcomes in patients with early psychosis compared to standard care (SC). METHODS: ACCESS III is a prospective non-randomized historical control design 1-year study examining the efficacy of EDIC (n = 120) vs. SC (n = 105) in patients aged 12-29 years. Primary outcome was the rate of ≥6 months combined symptomatic and functional remission. Additional outcomes comprised the reduction of DUP and course of psychopathology, functioning, quality of life, and satisfaction with care. RESULTS: In observed cases, 48.9% in the EDIC and 15.2% in the SC group reached the primary endpoint. Remission was predicted by EDIC (OR = 6.8, CI: 3.15-14.53, P < 0.001); younger age predicted non-remission (OR = 1.1, CI: 1.01-1.19, P = 0.038). Linear regressions indicated a reduction of DUP in EDIC (P < 0.001), but not in SC (P = 0.41). MMRMs showed significantly larger improvements in PANSS positive (P < 0.001) and GAF (P < 0.01) scores in EDIC vs. SC, and in EDIC over time in CGI-Severity (P < 0.001) and numerically in Q-LES-Q-18 (P = 0.052). CONCLUSIONS: EDIC lead to significantly higher proportions of patients achieving combined remission. Moderating variables included a reduction of DUP and EDIC, offering psychotherapeutic interventions.

Modeling psychiatric disorders: from genomic findings to cellular phenotypes.

Major programs in psychiatric genetics have identified >150 risk loci for psychiatric disorders. These loci converge on a small number of functional pathways, which span conventional diagnostic criteria, suggesting a partly common biology underlying schizophrenia, autism and other psychiatric disorders. Nevertheless, the cellular phenotypes that capture the fundamental features of psychiatric disorders have not yet been determined. Recent advances in genetics and stem cell biology offer new prospects for cell-based modeling of psychiatric disorders. The advent of cell reprogramming and induced pluripotent stem cells (iPSC) provides an opportunity to translate genetic findings into patient-specific in vitro models. iPSC technology is less than a decade old but holds great promise for bridging the gaps between patients, genetics and biology. Despite many obvious advantages, iPSC studies still present multiple challenges. In this expert review, we critically review the challenges for modeling of psychiatric disorders, potential solutions and how iPSC technology can be used to develop an analytical framework for the evaluation and therapeutic manipulation of fundamental disease processes.

Quality of patient care in the critical care unit in relation to nurse patient ratio: A descriptive study.

BACKGROUND: Intensive care is one of the most resource-intensive forms of medical care due to severely ill patients that are cared for in units with high staffing levels. Nursing's impact on the health of patients has shown that the number of nurses per patient and nurse education effects patient outcome. However, there are a lack of studies investigating highly specialised nurses in intensive care and their relation to patient outcome. METHOD: This is a retrospective study of critical care registry data (all patients >15 years) in general critical care units at seven university hospitals. RESULTS: Patient care and complications in relation to nurse/patient ratio showed that unplanned extubations occurred in 3-5.7% of cases. A difference between hospital patients' length of time on ventilation was found with the hospitals with the least amount of patients and with 0.5-0.6 specialist-nurse/patient a longer time on ventilation was noted. The length of ICU stay showed differences between the hospitals and nurse/patient ratios, with higher nurse/patient ratio with the longer length of ICU stay. CONCLUSION: Despite similarities between hospitals in relation to SAPS III on admission to critical care, there was a difference in nurse/patient ratios ranging from 1:1 to 0.5:1 and mean time on both invasive and noninvasive ventilation.