Background Hospital severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks are relevant for patients and healthcare systems within and beyond the pandemic. Aim To explore the characteristics of SARS-CoV-2 outbreaks and their infection prevention and control (IPC) measures during the different pandemic waves. Methods A comprehensive structured template for SARS-CoV-2 outbreaks was developed and filled out by six university hospitals. The main outcome variable was outbreak size (OS). Findings A total of 80 outbreaks and 734 infection cases were enrolled between March 2020 and February 2023. In the majority of outbreaks (85%) a contact tracing (CT) team was in place. In 13 (16%) outbreaks the CT team was exclusively responsible for CT, which was negatively linked to OS when adjusting for SARS-CoV-2 waves (estimate (beta) = -1.350; standard error (SE) = 0.274; P < 0.0001). Patients as index had a greater association with OS than healthcare workers (HCWs) (beta = -0.29; SE = 0.098; P = 0.003). Additionally, the mandatory use of face masks by patients in the presence of HCWs was negatively linked to OS (beta = -0.237; SE = 0.08; P = 0.003). The frequency of patient screening during outbreaks varied considerably, whereby higher frequency screenings for SARS-CoV-2 were negatively associated with OS (beta = -0.358; SE = 0.109; P = 0.001). Conclusion Our data provide insights in non-pharmaceutical outbreak prevention and management, revealing that the mandatory use of face masks by patients in the presence of HCWs and a high patient screening frequency in ongoing outbreaks were significantly associated with smaller outbreaks. Further studies are required to allow for generalizability.

INTRODUCTION:Emergency departments (EDs) are a critical entry gate for infectious agents into hospitals. In this interdisciplinary study, we explore how infection prevention and control (IPC) architectural interventions mitigate the spread of emerging respiratory pathogens using the example of SARS-CoV-2 in a prototypical ED. METHODS:Using an agent-based approach, we integrated data on patients' and healthcare workers' (HCWs) routines and the architectural characteristics of key ED areas. We estimated the number of transmissions in the ED by modelling the interactions between and among patients and HCWs. Architectural interventions were guided towards the gradual separation of pathogen carriers, compliance with a minimum interpersonal distance, and deconcentrating airborne pathogens (higher air exchange rates (AERs)). Interventions were epidemiologically evaluated for their mitigation effects on diverse endpoints. RESULTS:Simulation results indicated that higher AERs in the ED (compared with baseline) may provide a moderate level of infection mitigation (incidence rate ratio (IRR) of 0.95 (95% confidence interval (CI) 0.93-0.98)) while the overall burden decreased more when rooms in examination areas were separated (IRR of 0.78 (95% CI 0.76-0.81)) or when the size of the ED base was increased (IRR of 0.79 (95% CI 0.78-0.81)). The reduction in SARS-CoV-2-associated nosocomial transmissions was largest when architectural interventions were combined (IRR of 0.61 (95% CI 0.59-0.63)). CONCLUSIONS:These modelling results highlight the importance of IPC architectural interventions; they can be devised independently of profound knowledge of an emerging pathogen, focusing on technical, constructive, and functional components. These results may inform public health decision-makers and hospital architects on how IPC architectural interventions can be optimally used in healthcare premises.

PurposeUntil now, the Hospitalization Rate (HR) served as an indicator (among others) for the COVID-19 associated healthcare burden. To ensure that the HR accomplishes its full potential, hospitalizations caused by COVID-19 (primary cases) and hospitalizations of patients with incidental positive SARS-CoV-2 test results (incidental cases) must be differentiated. The aim of this study was to synthesize the existing evidence on differentiation criteria between hospitalizations of primary cases and incidental cases.MethodsAn online survey of the members of the German Network University Medicine (NUM) was conducted. Additionally, senior clinicians with expertise in COVID-19 care were invited for qualitative, semi-structured interviews. Furthermore, a rapid literature review was undertaken on publications between 03/2020 and 12/2022.ResultsIn the online survey (n=30, response rate 56%), pneumonia and acute upper respiratory tract infections were the most indicative diagnoses for a primary case. In contrast, malignant neoplasms and acute myocardial infarctions were most likely to be associated with incidental cases. According to the experts (n=6), the diagnosis, ward, and type of admission (emergency or elective), low oxygen saturation, need for supplemental oxygen, and initiation of COVID-19 therapy point to a primary case. The literature review found that respiratory syndromes and symptoms, oxygen support, and elevated levels of inflammatory markers were associated with primary cases.ConclusionThere are parameters for the differentiation of primary from incidental cases to improve the objective of the HR. Ultimately, an updated HR has the potential to serve as a more accurate indicator of the COVID-19 associated healthcare burden.

Abstract Background Characterizing clinical phenotypes is important for classifying patients, predicting disease outcomes, and adapting treatment. We aimed to identify distinct clinical phenotypes among hospitalized children and adolescents with SARS-CoV-2 infection and to evaluate variations in prognosis across these phenotypes. Methods The DGPI (German Society of Pediatric Infectious Diseases) registry serves as a nationwide, prospective registry for children and adolescents hospitalized with a SARS-CoV-2 infection in Germany. We applied hierarchical clustering and integrated variables such as sex, SARS-CoV-2-related symptoms, pre-existing comorbidities, clinically relevant coinfection, and SARS-CoV-2 risk factors to describe distinct clinical phenotypes. Subsequently, we applied a multinomial logistic regression model to examine the association between these phenotypes and discharge status. Results The DGPI registry encompassed 6983 patients and facilitated the identification of six distinct phenotypes for children and adolescents with SARS-CoV-2. Phenotype A had a similar symptom pattern as the total sample. Predominant symptoms of patients with other phenotypes were gastrointestinal (95.9%, B), asymptomatic (95.9%, C), lower respiratory tract (49.8%, D), lower respiratory tract and ear, nose and throat (86.2% and 41.7%, E), and neurological (99.2%, F). Patients with phenotype C had lower odds of residual symptoms (OR: 0.10 [0.06, 0.15]) than those with phenotype A, whereas patients with phenotype D and E had higher odds of residual symptoms (OR: 1.33 [1.11, 1.59] and 1.91 [1.65, 2.21], respectively) than those with phenotype A. Patients with phenotype D were significantly more likely (OR: 4.00 [1.95, 8.19]) to have an unfavorable outcome, compared to patients with phenotype A. Conclusions We could show that the identified phenotypes could facilitate early risk assessment and aid in tailoring individualized patient management strategies. Key messages • Six distinct clinical phenotypes existed in children and adolescents with SARS-CoV-2 infection. • Phenotypes could assist in risk evaluation and help personalize patient care.

Background: Bacterial infection ranks amongst the most common causes of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT). Although ciprofloxacin (CIP) prophylaxis is recommended, information on serum levels and clinical course is lacking.Aim: To investigate relationships between CIP level and failure of prophylaxis, particularly in terms of whether different pharmacokinetic (PK) indices [area under the concentration -time curve (AUC(0-24h)) vs single time samples] correlate differently with the outcome.Methods: This prospective observational monocentric study was conducted at a 1500-bed teaching hospital (March 2018 -March 2019), including 63 adult patients with alloHSCT receiving CIP prophylaxis. Blood samples were drawn at three sampling times (1, 6 and 12 h post-administration), twice per week, and measured via high performance liquid chromatography. The onset of febrile episodes (FEBs) indicated suspected failure of CIP prophylaxis. Positive blood cultures [bloodstream infection (BSI)] indicated confirmed failure of prophylaxis.Findings: Seven of 63 patients died without significant differences in their average CIP levels compared with survivors, with patients experiencing FEBs (54/63) displaying a 13% [95% confidence interval (CI) 4-22%] lower probability of survival. In total, 225 sets of three values (triplets) were obtained from 58 primary CIP episodes. Triplets preceding BSI with Gram-negative bacteria (GNB-BSI) showed lower AUC(0-24h) on average, but similar single time sample indices. An AUC(0-24h) of <= 21.61 mgh/L resulted in four-fold higher odds of GNB-BSI (adjusted odds ratio 3.96, 95% CI 1.21-13.00). These results were independent of the administration route, patient demographics or sampling protocol deviations, indi-cating reduced CIP exposure upon GNB-BSI events.Conclusion: Monitoring CIP levels, using multiple sampling times, may be useful to reduce alloHSCT-associated bacterial infections. Further analysis is needed to investigate causality.2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Background The aim of this study was to analyze the cleaning and disinfection of operating rooms (ORs) status quo focusing on hygiene plans in German hospitals. Methods In 2016, a structured online survey was sent to infection prevention and control (IPC) specialists at the cost calculation hospitals of the Institute for the Hospital Remuneration System (InEK) and all university hospitals in Germany (n = 365). Results With a response rate of 27.4%, 78% stated that written hygiene plans were available. After cleaning and disinfecting an OR with a "septic" patient, 55% waited until surfaces were dry before reusing in accordance with national recommendations, 27% waited > 30 min. Additionally, 28% of hospitals had ORs only for "septic" patients. In 56% "septic" patients were only operated on at the end of the program. Postoperative monitoring of patients with bacteria with special IPC requirements took place in the post anesthesia care unit (PACU) (29%), operating room (OR) (52%), intensive care unit (ICU) (53%), and in the intermediate care unit (IMC) (19%). Discussion and conclusions Despite written hygiene plans in place the partly long duration of OR nonuse time following IPC measures, the consistent continued use of stratification for "septic" patients and the postoperative follow-up care of patients with colonizing/infecting bacteria with special IPC requirements in the OR and high care areas represent relevant potential for improvement.

Background: More than 160,000 central-line-associated bloodstream infections (CLABSIs) are estimated for Europe each year, leading to about 25,000 deaths. Aim: To characterize the contamination of administration sets in suspected CLABSI cases in the intensive care unit (ICU). Methods: In ICU patients (from February 2017 to February 2018) with suspected CLABSI, all sampled central venous catheters (CVCs) were examined in four segments (from CVC tip to connected tubing systems) for contamination. A risk factor analysis using binary logistic regression was performed. Findings: Fifty-two consecutively sampled CVCs with 1004 elements were analysed with 45 elements being positive for at least one micro-organism (4.48%). There was a significant association with the duration of catheterization (P 1/4 0.038, N 1/4 50) with a daily increase of contamination risk by 11.5% (odds ratio: 1.115). The mean number of CVC manipulations was 40 within 72 h (standard deviation: 20.5), with no association with contamination risk (P 1/4 0.381). The contamination risk of the CVC segments decreased from proximal to distal. Non-replaceable components of the CVC had a high risk (14 times higher; P 1/4 0.01). A significant positive correlation was detected between positive tip cultures and microbial growth in the administration set (r(49) 1/4 0.437; P 1/4 0.001). Conclusion: Although only a minority of CLABSI-suspect patients had positive blood cultures, the contamination rate of CVCs and administration set was high, possibly indicating a relevant underreporting. The finding of identical species in adjacent segments underlines the role of upward or downward spread of micro-organisms within the tubes; therefore, aseptic tasks should be emphasized. & COPY; 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Einleitung Subkutan implantierbare venöse Zugänge (TIVAD totally implantable venous access device; Port-Katheter) sind von großer Bedeutung in der Behandlung von Patienten mit fortgeschrittenen gastrointestinalen Malignomen. TIVADs bieten einen sicheren Zugang zum zentralen Gefäßsystem und ermöglichen die zuverlässige Anwendung von Zytostatika, Medikamenten oder parenteraler Ernährung. Trotz ihrer Sicherheit und Verträglichkeit sind TIVADs mit potenziell schweren Komplikationen verbunden. Dazu gehören Infektionen, die zum Abbruch von Zytostatika-Therapien, zu Hospitalisierung, zu erhöhter Morbidität und Mortalität sowie steigenden Kosten im Gesundheitswesen führen.

Background: In contrast to the beginning of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), pandemic, more and more hospital issues are now regulated by policy. Aim: To identify differences between expert recommendations and legal requirements regarding infection prevention and control (IPC) strategies. Methods: A cross-sectional study was conducted between 29th September 2022 and 3rd November 2022 addressing 1319 members of the German Society for Hygiene and Micro-biology. The response rate was 12%. This paper reports the expert recommendations on different IPC strategies. Findings: The majority (66%) of experts recommended universal mask usage, with 34% recommending it seasonally, even after the SARS-CoV-2 pandemic. Medical microbiology (MM) experts were more likely to recommend continuing to wear the masks indefinitely compared with IPC experts. Concerning the mask type, medical masks were recommended more frequently by IPC experts (47.3%), while FFP2 masks were preferred by MM experts (31.8%). The majority (54.7%) of experts recommended universal screening of employees, mainly in settings with extremely vulnerable patients and if regional incidence rates were high, at a frequency of twice per week. The dominant advice (recommended by at least 50% of experts) for employees exposed to SARS-CoV-2 was daily testing and wearing a mask, regardless of the length of exposure. Conclusions: Expert recommendations deviate from the legal requirements and appear to be more differentiated and proportional. The influence of specific experience and expertise on mask recommendations should be investigated in more detail. For relevant policy decisions, a quick, focused and broad-based consultation of expertise could be of added value. 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Drinking water in hospitals is often tested for Pseudomonas aeruginosa because of its virulence potential. This article describes a case where, based on EN ISO 16266, seven of 11 (64%) samples taken simultaneously from the drinking water system at a single hospital tested positive for P. aeruginosa. This resulted in extensive investigations and interventions, and a number of measures were implemented. However, supplementary analyses with more discriminatory power (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S-rRNA sequencing) ruled out P. aeruginosa completely. The authors wish to raise awareness of this problem, and suggest that diagnostic uncertainty of results obtained by EN ISO 16266 should be indicated on laboratory reports. Wrongly assuming the presence of P. aeruginosa in hospital water supply systems can lead to unnecessary control measures, as analytical uncertainty massively influences the health risk assessment and the remediation measures initiated in medical environments.

Background: Patients are at risk of nosocomial COVID-19 infection. The role of accompanying persons/visitors as potential infection donors is not yet well researched, but the risk will be influenced by prevention measures recommended by infection control practitioners. Aim: To collect information about COVID-19 infection control strategies for patients and accompanying persons from infection control practitioners in German hospitals. Methods: A cross-sectional questionnaire was developed, ethically approved, pre-tested and formatted as an online tool. Infection control practitioners in 987 randomly selected German hospitals were invited to participate in March and April 2021. For statistical analysis, the hospitals were categorized as small (0-499 beds) or large (>= 500 beds). Findings: One hundred surveys were completed (response rate: 10%). A higher proportion of large (71%) than small (49%) hospitals let patients decide freely whether to wear medical or FFP2 masks. Most hospitals reported spatial separation for COVID-19 patients and non-COVID-19 cases (38%) or additionally for suspected COVID-19 cases (53%). A separation of healthcare teams for these areas existed in 54% of the hospitals. Accompaniment bans were more prevalent in large (52%) than in small hospitals (29%), but large hospitals granted more exemptions. Conclusion: The decision as to whether to separate areas and teams seemed to depend on the hospital's structural conditions, therefore impairing the implementation of recommendations. Accompaniment regulations differ between hospital sizes and may depend on patient numbers, case type/severity and patients' requirements. In the dynamic situation of a pandemic, it can be difficult to stay up to date with findings and recommendations on infection control. (C) 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Background: Healthcare-associated infections are a major burden for hospitals, leading to morbidity and mortality and unnecessary medical costs. They can probably be reduced through what is known as patient empowerment. This study aims to address the question of whether patients are interested in receiving infection prevention and control information.Methods: Patients were asked in structured interviews whether they would like more information on infection prevention and control. Inclusion criteria comprised 2 groups of patients. Group 1 were patients undergoing elective total endoprosthesis (TEP) and Group 2 were patients tested positive for meticillin-resistant Staphylococcus aureus (MRSA).Results: The response rate was 38.4 % (163/425 patients). Approximately 75 % of the patients were interested in information on infection prevention and control. The topics of interest differed between the two patient groups: MRSA patients had a higher need for infection prevention and control information. TEP patients showed a high acceptance of antiseptic body wash and a willingness to pay for it themselves. Information given to patients should be group-specific and timely.Conclusion: Our data suggest a lack of information on infection prevention and control among patients and underline the importance of patient empowerment. The willingness of patients to pay personally for antiseptic wash should be assessed further. on behalf of The Healthcare Infection Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Oncologists face challenges in the management of SARS-CoV-2 infections and post-SARS-CoV-2 cancer treatment. We analyzed diagnostic, clinical and post-SARS-CoV-2 scenarios in patients from three German cancer centers with RT-PCR confirmed SARS-CoV-2 infection. Sixty-three patients with SARS-CoV-2 and hematologic or solid neoplasms were included. Thirty patients were initially asymptomatic, 10 of whom developed COVID-19 symptoms subsequently. Altogether 20 (32%) patients were asymptomatic, 18 (29%) had mild, 12 (19%) severe and 13 (20%) critical courses. Lymphocytopenia increased risk of severe/critical COVID-19 three-fold (p = 0.015). Asymptomatic course was not associated with age, remission status, therapies or co-morbidities. Secondary bacterial infection accompanied more than one third of critical COVID-19 cases. Treatment was delayed post-SARS-CoV-2 in 46 patients, 9 of whom developed progressive disease (PD). Cancer therapy was modified in 8 SARS-CoV-2 survivors because of deteriorating performance or PD. At the last follow-up, 17 patients had died from COVID-19 (n = 8) or PD (n = 9) giving an estimated 73% four-month overall survival rate. SARS-CoV-2 infection has a heterogenous course in cancer patients. Lymphocytopenia carries a significant risk of severe/critical COVID-19. SARS-CoV-2 disruption of therapy is as serious as SARS-CoV-2 infection itself. Careful surveillance will allow early restart of the anti-cancer treatment.

Background: SARS-CoV-2 vaccination for healthcare workers (HCWs) started in Germany in December 2020. Hospitals had little time to prepare a vaccination strategy. Aim: To gather information on the initial vaccination strategy for HCWs from the infection control practitioners in Germany. Methods: A cross-sectional, ethically approved questionnaire was developed, formatted as an online survey and pre-tested. Infection control practitioners responsible for hygiene/ infection prevention in 987 randomly selected German hospitals were invited to participate in the survey in March and April 2021. For statistical analysis, the hospitals were categorized into two groups based on bed capacity (<500 beds: small; >500 beds: large). Findings: One hundred out of 987 (10%) infection control practitioners completed the survey. In 80% of the participating hospitals, HCW vaccination prioritization was based on recommendations of the German standing committee on vaccination (STIKO). Even so, only 54% prioritized the vaccination of HCWs with contact to vulnerable patients, thus deviating from STIKO recommendations. HCWs with a high personal health risk were prioritized for vaccination in 24% of the hospitals. Transferring unvaccinated HCWs to an area with less infection risk was considered by 2% of large and 12% of small hospitals. Conclusion: Vaccination prioritization differed across hospitals and deviated from STIKO recommendations. A pandemic preparedness concept should address the potential impact of divergent strategies compared to a common approach. In addition, further studies analysing the reasons why HCWs remain unvaccinated are needed to adopt effective strategies. This is especially important against the background of facility-based compul-sory vaccination. (c) 2022 Published by Elsevier Ltd on behalf of The Healthcare Infection Society.

In the Northern Hemisphere, the SARS-CoV-2 pandemic has been successfully contained in some countries, at least temporarily, although the current variants of concern are more infectious. For the example of Germany, the change toward a slowdown in the rate of infection coincided with an increase in temperature and sunshine duration, but also with a massive rollout of rapid antigen testing, i.e., AG-PoC (antigen point of care) as part of the national testing strategy with one free test per week for every citizen. The large-scale introduction of Ag-PoC testing occurred in parallel with a steady rate of vaccination and a continuation of other public health interventions such as social distancing, mask wearing, contact tracing, and quarantine. The purpose of this viewpoint is to assess the risk of infection in individuals who tested negative by AG-PoC. The operating principle of AG-PoC testing is to break chains of infection by identifying asymptomatic or presymptomatic infected individuals, assuming initiation of quarantine of individuals who test positive by AG-PoC, in addition to contact tracing. Due to the lower sensitivity of AG-PoC, the diagnostic interval is shortened compared to the gold standard of PCR. However, the diagnostic window correlates with the phase of highest infectivity. One issue to consider in this context is the limit of detection (LOD) of commercially available Ag-PoC kits. Literature review gives a range for LOD of 104 to 106 viral copies/mL of exhaled fluid [see for example 1]. While the typical viral load for the alpha variant is 108.5 [2]. This suggests that with AG-PoC and the application of quarantine to identified individuals, the viral load in the general population is reduced by a factor of up to 10,000 or more for the delta variant. It should be noted that similar effects are also expected for vaccinated individuals in case of infection, although the range for the viral load are yet to be known.

AbstractDetailed knowledge of the properties of exhaled particles from the human respiratory tract for all genders and ages is essential to determine the modes of transmission of airborne diseases. This applies not only to the current COVID-19 pandemic, but also to many others, be it measles, seasonal influenza or tuberculosis. To date, there are no data on the individual-specific concentrations and sizes of exhaled particles over the entire size range from nanometre to millimetre. Here we present a comprehensive data set, measured by particle size spectrometry and in-line holography covering the entire size range from 132 healthy volunteers aged 5 to 80 years for a defined set of breathing and vocalisation activities. We find age to have a large effect on small particle concentrations (<5 µm), doubling in children during adolescence and in adults over a 30-year period. In contrast, gender, body mass index, smoking or exercise habits have no discernible influence. Particles >20 µm show on average no measurable dependence on the type of vocalisation with the exception of shouting. We show evidence that particles <5 µm mainly originate in the lower respiratory tract, 5-15 µm in the larynx/pharynx, and >15 µm in the oral cavity.

Pathogen outbreaks (i.e., outbreaks of bacteria and viruses) in hospitals can cause high mortality rates and increase costs for hospitals significantly. An outbreak is generally noticed when the number of infected patients rises above an endemic level or the usual prevalence of a pathogen in a defined population. Reconstructing transmission pathways back to the source of an outbreak - the patient zero or index patient - requires the analysis of microbiological data and patient contacts. This is often manually completed by infection control experts. We present a novel visual analytics approach to support the analysis of transmission pathways, patient contacts, the progression of the outbreak, and patient timelines during hospitalization. Infection control experts applied our solution to a real outbreak of Klebsiella pneumoniae in a large German hospital. Using our system, our experts were able to scale the analysis of transmission pathways to longer time intervals (i.e., several years of data instead of days) and across a larger number of wards. Also, the system is able to reduce the analysis time from days to hours. In our final study, feedback from twenty-five experts from seven German hospitals provides evidence that our solution brings significant benefits for analyzing outbreaks.

Background Health workers face a higher risk of infection during the COVID-19 pandemic than the average population, yet we know very little on how protection is managed in daily practice. The aim of this study is to contribute new empirical data on the management of protection in clinical settings with a focus on surveillance, using Germany as case study. Methods We draw on material gathered in multi-centre hospital surveillance online surveys in Germany, which are part of a national COVID-19 University Research Network (project B-FAST). Selected indicators include tools, strategies and access to protection, with a focus on the composition of new surveillance teams; n = 100 responses, comprising n = 33/92% of all university medical centres; n = 67/18% of participating hospitals in two German Federal States in March 2021. Results Three major strategies of protection were identified: expanding services, information and access for all health workers in the clinical setting; establishing novel surveillance teams to protect hospital employees comprising hotline, testing and tracing teams; creating large-scale in-house vaccination programs in accordance with national vaccination prioritisation policy of health workers. The composition of the surveillance teams showed high variation in relation to professional groups/skills and status. In particular, hospital hygienists (often with a professional background in nursing) were included in all teams, but their share varied from only 24% in testing to 60% in hotline and even 95% in tracing teams. Conclusions German hospitals have stepped up efforts to protect health workers primarily through comprehensive surveillance and personal protection including vaccination. Our findings reveal capacity for innovation in the management of protection especially in two areas: improving the skill-mix and leadership of surveillance teams, and strengthening the role of hospital hygienists in surveillance. Key messages The building of interdisciplinary hospital surveillance teams plays an important role in innovating surveillance and strengthening protection. The skill-mix and leadership of the surveillance teams need further research and policy investigation to improve efficiency.