Implementation of a digital diary in the intensive care unit; understanding the facilitators and barriers: A qualitative exploration.

BACKGROUND: In the recent years, digital intensive care unit (ICU) diaries have emerged as more advantageous than paper diaries. Despite the advantages of digital diaries, the successful implementation and maintenance of this digital intervention present significant challenges in clinical practice. Therefore, understanding the facilitators and barriers among stakeholders influencing this process becomes imperative for devising a tailored strategy to integrate digital diaries effectively within ICU settings. AIM/OBJECTIVE: The aim of this study was to explore facilitators and barriers for implementation of a digital ICU diary from the perspectives of ICU professionals, ICU survivors, and their relatives. METHODS: A qualitative design was used, incorporating focus-group interviews with professionals from four Dutch ICUs, along with individual interviews with ICU survivors and relatives. The study spanned from October 2022 to April 2023. Data analysis utilised a mixed inductive-deductive approach, particularly through directed content analysis. The Consolidated Framework for Implementation Research 2.0 guided both data collection and analysis processes. FINDINGS: We conducted five focus-group interviews among ICU professionals (n = 32) and 10 individual or dual interviews involving five ICU survivors and nine relatives. Key facilitators for implementing a digital diary according to ICU professionals encompassed a user-friendly interface accessible independent of time and place, with a seamless login process requiring minimal steps, comprehensive training covering all aspects of its use, and feedback from the experiences of both patients and relatives. Barriers for ICU professionals included many steps required to access the digital diary, as well as resistance to (co)writing diary entries. In contrast, professionals' involvement in writing diary entries was highly appreciated among ICU survivors and relatives. An ambiguous factor arose regarding sharing the digital diary with others; both ICU survivors and relatives found it valuable, yet it also raised privacy concerns. CONCLUSIONS: This study offers insights into the most important factors influencing the implementation of a digital ICU diary. Strikingly, some factors serve as both barriers and facilitators. When developing the implementation strategy, the identified facilitators can be used to overcome the barriers faced by ICU professionals, ICU survivors, and their relatives in adopting a digital diary.

Flow-controlled ventilation decreases mechanical power in postoperative ICU patients.

BACKGROUND: Mechanical power (MP) is the energy delivered by the ventilator to the respiratory system and combines factors related to the development of ventilator-induced lung injury (VILI). Flow-controlled ventilation (FCV) is a new ventilation mode using a constant low flow during both inspiration and expiration, which is hypothesized to lower the MP and to improve ventilation homogeneity. Data demonstrating these effects are scarce, since previous studies comparing FCV with conventional controlled ventilation modes in ICU patients suffer from important methodological concerns. OBJECTIVES: This study aims to assess the difference in MP between FCV and pressure-controlled ventilation (PCV). Secondary aims were to explore the effect of FCV in terms of minute volume, ventilation distribution and homogeneity, and gas exchange. METHODS: This is a physiological study in post-cardiothoracic surgery patients requiring mechanical ventilation in the ICU. During PCV at baseline and 90 min of FCV, intratracheal pressure, airway flow and electrical impedance tomography (EIT) were measured continuously, and hemodynamics and venous and arterial blood gases were obtained repeatedly. Pressure-volume loops were constructed for the calculation of the MP. RESULTS: In 10 patients, optimized FCV versus PCV resulted in a lower MP (7.7 vs. 11.0 J/min; p = 0.004). Although FCV did not increase overall ventilation homogeneity, it did lead to an improved ventilation of the dependent lung regions. A stable gas exchange at lower minute volumes was obtained. CONCLUSIONS: FCV resulted in a lower MP and improved ventilation of the dependent lung regions in post-cardiothoracic surgery patients on the ICU. Trial registration Clinicaltrials.gov identifier: NCT05644418. Registered 1 December 2022, retrospectively registered.

Opportunities and barriers for prehospital emergency medical services research in the Netherlands; results of a mixed-methods consensus study.

INTRODUCTION: Quality improvement in prehospital emergency medical services (EMS) can only be achieved by high-quality research and critical appraisal of current practices. This study examines current opportunities and barriers in EMS research in the Netherlands. METHODS: This mixed-methods consensus study consisted of three phases. The first phase consisted of semi-structured interviews with relevant stakeholders. Thematic analysis of qualitative data derived from these interviews was used to identify main themes, which were subsequently discussed in several online focus groups in the second phase. Output from these discussions was used to shape statements for an online Delphi consensus study among relevant stakeholders in EMS research. Consensus was met if 80% of respondents agreed or disagreed on a particular statement. RESULTS: Forty-nine stakeholders participated in the study; qualitative thematic analysis of the interviews and focus group discussions identified four main themes: (1) data registration and data sharing, (2) laws and regulations, (3) financial aspects and funding, and (4) organization and culture. Qualitative data from the first two phases of the study were used to construct 33 statements for an online Delphi study. Consensus was reached on 21 (64%) statements. Eleven (52%) of these statements pertained to the storage and use of EMS patient data. CONCLUSION: Barriers for prehospital EMS research in the Netherlands include issues regarding the use of patient data, privacy and legislation, funding and research culture in EMS organizations. Opportunities to increase scientific productivity in EMS research include the development of a national strategy for EMS data and the incorporation of EMS topics in research agendas of national medical professional associations.

The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19.

INTRODUCTION: Midazolam-based continuous intravenous sedation in patients admitted to the intensive care unit (ICU) was a necessity during the COVID-19 pandemic. However, benzodiazepine-based sedation is associated with a high incidence of benzodiazepine-related delirium and additional days on mechanical ventilation. Due to the requirement of high midazolam doses in combination with the impaired renal clearance (CL) of the pharmacological active metabolite 1-OH-midazolam-glucuronide (10% compared to midazolam), ICU patients with COVID-19 and continuous renal replacement therapy (CRRT) were at risk of unintended prolonged sedation. Several CRRT-related factors may have influenced the delivered CL of midazolam and its metabolites. Therefore, the aim of the study was to identify and describe these CRRT-related factors. METHODS: Pre-filter blood samples and ultrafiltrate samples were collected simultaneously. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide plasma samples were analyzed using an UPLC-MS/MS method. The prescribed CRRT dose was corrected for downtime and filter integrity using the urea ratio (urea concentration in effluent/urea concentration plasma). CL of midazolam and its metabolites were calculated with the delivered CRRT dose (corrected for downtime and saturation coefficient [SD]). RESULTS: Three patients on continuous venovenous hemodialysis (CVVHD) and 2 patients on continuous venovenous hemodiafiltration (CVVHDF) were included. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations were 2,849 (0-6,700) µg/L, 153 (0-295) µg/L, and 27,297 (1,727-39,000) µg/L, respectively. The SD was 0.03 (0.02-0.03) for midazolam, 0.05 (0.05-0.06) for 1-OH-midazolam, and 0.33 (0.23-0.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0-1.7) mL/min for midazolam, 2.7 (0-3.5) mL/min for 1-OH-midazolam, and 15.7 (4.0-27.7) mL/min for 1-OH-midazolam-glucuronide. CONCLUSIONS: Midazolam and 1-OH-midazolam were not removed during CVVHD and CVVHDF. However, 1-OH-midazolam-glucuronide was removed reasonably, approximately up to 43%. CRRT modality, filter integrity, and downtime affect this removal. These data imply a personalized titration of midazolam in critically ill patients with renal failure and awareness for the additional sedative effects of its active metabolites.

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial.

BACKGROUND: The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae. METHODS: This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization. RESULTS: The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73-1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18-0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12-1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29-1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22-2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study. CONCLUSIONS: Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov (#NCT03628391), October 9, 2017.

Effect of a music intervention on anxiety in adult critically ill patients: a multicenter randomized clinical trial.

BACKGROUND: Previous studies show positive effect of music on reducing anxiety, pain, and medication requirement. Anxiety has become a more pertinent issue in the intensive care unit (ICU) since wakefulness is preferred according to recent guidelines. Nevertheless, evidence on the effect of music in ICU patients is scarce. Therefore, we studied the effect of music intervention on anxiety in ICU patients. METHODS: A multicenter randomized clinical trial was conducted between August 2020 and December 2021 in ICU's at an academic medical centre and two regional hospitals. Adult critically ill patients were eligible when hemodynamically stable and able to communicate (Richmond agitation-sedation scale (RASS) of at least - 2). Patients in the intervention arm were offered music twice daily during three days for at least 30 min per session. Patients in the control group received standard care. The primary outcome was anxiety level assessed with the visual analogue scale for anxiety [VAS-A; range 0-10] twice daily (morning and evening). Secondary outcomes included; 6-item state-trait anxiety inventory (STAI-6), sleep quality, delirium, heart rate, mean arterial pressure, pain, RASS, medication, ICU length of stay, patients' memory and experience of ICU stay. RESULTS: 94 patients were included in the primary analysis. Music did not significantly reduce anxiety (VAS-A in the intervention group; 2.5 (IQR 1.0-4.5), 1.8 (0.0-3.6), and 2.5 (0.0-3.6) on day 1, 2, and 3 vs. 3.0 (0.6-4.0), 1.5 (0.0-4.0), and 2.0 (0.0-4.0) in the control group; p > 0.92). Overall median daily VAS-A scores ranged from 1.5 to 3.0. Fewer patients required opioids (21 vs. 29, p = 0.03) and sleep quality was lower in the music group on study day one [5.0 (4.0-6.0) vs. 4.5 (3.0-5.0), p = 0.03]. Other outcomes were similar between groups. CONCLUSIONS: Anxiety levels in this ICU population were low, and music during 3 days did not decrease anxiety. This study indicates that efficacy of music is context and intervention-dependent, given previous evidence showing decreased anxiety. Trial registration Netherlands Trial Register: NL8595, Registered, 1 April 2020. CLINICALTRIALS: gov ID: NCT04796389, Registered retrospectively, 12 March 2021.

Optimal Dosing and Timing of High-Dose Corticosteroid Therapy in Hospitalized Patients With COVID-19: Study Protocol for a Retrospective Observational Multicenter Study (SELECT).

BACKGROUND: In hospitalized patients with COVID-19, the dosing and timing of corticosteroids vary widely. Low-dose dexamethasone therapy reduces mortality in patients requiring respiratory support, but it remains unclear how to treat patients when this therapy fails. In critically ill patients, high-dose corticosteroids are often administered as salvage late in the disease course, whereas earlier administration may be more beneficial in preventing disease progression. Previous research has revealed that increased levels of various biomarkers are associated with mortality, and whole blood transcriptome sequencing has the ability to identify host factors predisposing to critical illness in patients with COVID-19. OBJECTIVE: Our goal is to determine the most optimal dosing and timing of corticosteroid therapy and to provide a basis for personalized corticosteroid treatment regimens to reduce morbidity and mortality in hospitalized patients with COVID-19. METHODS: This is a retrospective, observational, multicenter study that includes adult patients who were hospitalized due to COVID-19 in the Netherlands. We will use the differences in therapeutic strategies between hospitals (per protocol high-dose corticosteroids or not) over time to determine whether high-dose corticosteroids have an effect on the following outcome measures: mechanical ventilation or high-flow nasal cannula therapy, in-hospital mortality, and 28-day survival. We will also explore biomarker profiles in serum and bronchoalveolar lavage fluid and use whole blood transcriptome analysis to determine factors that influence the relationship between high-dose corticosteroids and outcome. Existing databases that contain routinely collected electronic data during ward and intensive care admissions, as well as existing biobanks, will be used. We will apply longitudinal modeling appropriate for each data structure to answer the research questions at hand. RESULTS: As of April 2023, data have been collected for a total of 1500 patients, with data collection anticipated to be completed by December 2023. We expect the first results to be available in early 2024. CONCLUSIONS: This study protocol presents a strategy to investigate the effect of high-dose corticosteroids throughout the entire clinical course of hospitalized patients with COVID-19, from hospital admission to the ward or intensive care unit until hospital discharge. Moreover, our exploration of biomarker and gene expression profiles for targeted corticosteroid therapy represents a first step towards personalized COVID-19 corticosteroid treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT05403359; https://clinicaltrials.gov/ct2/show/NCT05403359. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48183.

[Monkeypox, a new pandemic?] / Uitbraak van monkeypox: een nieuwe pandemie?

Monkeypox (MPX) is a disease caused by the monkeypox virus. It is a viral zoonotic disease, endemic in Central and West Africa. Human-to-human spread also occurs and is a feature of the current global outbreak. As far as we know, exponential transmission during this outbreak is not related to changed viral characteristics but due to multiple high-risk contacts in a subset of people that have contracted the virus, so far almost exclusively affecting men who have sex with men (MSM). Appropriate public health measures and increased alertness of all health care providers is needed to increase case-finding and decrease transmission. There is a real chance of MPX to become endemic in large parts of the world.

Development and validation of an early warning model for hospitalized COVID-19 patients: a multi-center retrospective cohort study.

BACKGROUND: Timely identification of deteriorating COVID-19 patients is needed to guide changes in clinical management and admission to intensive care units (ICUs). There is significant concern that widely used Early warning scores (EWSs) underestimate illness severity in COVID-19 patients and therefore, we developed an early warning model specifically for COVID-19 patients. METHODS: We retrospectively collected electronic medical record data to extract predictors and used these to fit a random forest model. To simulate the situation in which the model would have been developed after the first and implemented during the second COVID-19 'wave' in the Netherlands, we performed a temporal validation by splitting all included patients into groups admitted before and after August 1, 2020. Furthermore, we propose a method for dynamic model updating to retain model performance over time. We evaluated model discrimination and calibration, performed a decision curve analysis, and quantified the importance of predictors using SHapley Additive exPlanations values. RESULTS: We included 3514 COVID-19 patient admissions from six Dutch hospitals between February 2020 and May 2021, and included a total of 18 predictors for model fitting. The model showed a higher discriminative performance in terms of partial area under the receiver operating characteristic curve (0.82 [0.80-0.84]) compared to the National early warning score (0.72 [0.69-0.74]) and the Modified early warning score (0.67 [0.65-0.69]), a greater net benefit over a range of clinically relevant model thresholds, and relatively good calibration (intercept = 0.03 [- 0.09 to 0.14], slope = 0.79 [0.73-0.86]). CONCLUSIONS: This study shows the potential benefit of moving from early warning models for the general inpatient population to models for specific patient groups. Further (independent) validation of the model is needed.

Complementarity of International Instruments in the Field of Biosecurity.

The COVID-19 pandemic has demonstrated the devastating impact of infectious disease outbreaks and the threat of emerging and re-emerging dangerous pathogens, independent of their origin. Natural, accidental, and deliberate disease outbreaks all need systems in place for an effective public health response. The best known international instrument in the field of public health is the WHO International Health Regulations (2005). Although the International Health Regulations are mainly focused on natural disease outbreaks, the actions to take to comply with them also contribute to biosecurity and non-proliferation. This paper examines in case of full implementation of the International Health Regulations, what other actions states should take to comply with international biosecurity instruments, including the Biological and Toxin Weapons Convention and United Nations Security Council Resolution 1540, to effectively prevent and defend against intentional biological threats. An overview of international instruments from different disciplines regarding biosecurity is presented. Furthermore, this paper clarifies the similarities between the international biosecurity instruments and addresses the additional requirements that instruments stipulate. From a detailed comparison between the instruments it can be concluded that, to adhere to all legally-binding international biosecurity instruments, specific non-proliferation and export control measures are necessary in addition to full implementation of the International Health Regulations. Additionally, an overview of non-legally binding instruments in the field of biosecurity is presented and practical implementation examples are highlighted. Compliance with legally binding instruments can be improved by precise guidance provided by non-legally binding instruments that are clear and attuned to the situation on the ground. To improve understanding of the existing international instruments, this paper aims to provide an overview of the international legal biosecurity framework to biosecurity experts, policymakers, civil servants, and practitioners. It offers possible practical applications for the politico-legal context and accommodates the enhancement of full employment of biosecurity resources for an improved multidisciplinary capacity to prevent, detect, and respond to infectious disease outbreaks.

Long-Term Clinical Performance of an Uncemented, Mobile Bearing, Anterior Stabilized Knee System and the Impact of Previous Knee Surgery.

BACKGROUND: The aim of this study is to report long-term survival and patient-reported outcome measures (PROMs) of the uncemented low contact stress total knee system and explore the potential association between prior knee surgery and outcomes. METHODS: A total of 1,289 procedures in 1,068 patients performed between 2000 and 2010 (mean follow-up 11.1 years) were retrospectively identified. All patients received an uncemented, mobile bearing, anterior stabilized (cruciate sacrificing) knee implant with a porous coating on the bone-prosthesis surface. Implant survival was calculated using competing risk analyses at 5, 10, and 15 years. PROMs include the Oxford Knee Score, Knee Society Score (domain function), EuroQol 5D-3L, and Numeric Rating Scale for pain during rest and activity, and for overall satisfaction. The association between previous surgery (no surgery versus meniscectomy versus arthroscopy versus corrective osteotomies) and implant survival was assessed with multivariable Cox proportional hazards analysis; the association with PROMs was assessed with multivariable linear regression analyses. RESULTS: Survival after 5, 10, and 15 years was 97.0% (95% CI 96.0-98.0), 96.3% (95% CI 95.3-97.3), and 96.0% (95% CI 94.8-97.2), respectively. The most common reason for revision was aseptic loosening of the tibial tray (23/49 revisions, 47%). All PROMs were comparable with the reference values of the Dutch Arthroplasty Register. History of knee surgery prior to TKA was not associated with survival or PROMs. CONCLUSION: The low contact stress uncemented mobile bearing knee implant provides excellent survival and patient satisfaction in our cohort. Previous surgery does not seem to compromise results in our population.

Eighteen-Year Outcome of an Uncemented "Meniscal Bearing", Cruciate-Retaining Total Knee System.

BACKGROUND: The aim of this study is to evaluate the survival, radiographic, and functional outcomes of the uncemented "meniscal bearing" cruciate-retaining Low Contact Stress (LCS) (DePuy Synthes, Warsaw, IN, USA) total knee system after a long-term follow-up period. METHODS: A total of 56 patients (67 knees) who received an uncemented "meniscal bearing" cruciate-retaining LCS total knee system between 2000 and 2005 were retrospectively reviewed. Patients were 64 ± 7 years old with osteoarthritis as the indication for arthroplasty. The survivorship, radiographs, and patient-reported outcome measures (PROMs) were analyzed. RESULTS: The all-cause survival after 5, 10, 15, and 18 years was 97.0%, 93.8%, 92.0%, and 92.0%, respectively. Survival with revision for aseptic loosening as an end point was 98.4% at 5 years and 96.7% at 10, 15, and 18 years. Reasons of revisions and their interventions consisted of anterior knee pain requiring secondary patellar resurfacing (n = 3, 60%), polyethylene wear requiring an insert exchange (n = 2, 40%), and bearing spin-out requiring an insert exchange (n = 1, 20%). Two of the 5 revision cases developed aseptic loosening of the tibial component later on during the study period. A radiographic analysis demonstrated radiolucent lines in 14/47 implants (30%) after 12.0 ± 3.8 years, but were not revised, respectively. After a mean follow-up of 18.5 years, PROMs (n = 20) were found comparable with the 1-year postoperative PROMs of all implants reported by the LROI (Dutch Arthroplasty Register). CONCLUSION: This present study demonstrates good results of the uncemented "meniscal bearing" cruciate-retaining LCS total knee system toward survival and functional outcomes after a long-term median follow-up of 17.5 years. LEVEL OF EVIDENCE: Therapeutic retrospective cohort study, LEVEL III.

Hyperinflammation Reduces Midazolam Metabolism in Critically Ill Adults with COVID-19.

BACKGROUND AND OBJECTIVE: Many patients treated for COVID-19 related acute respiratory distress syndrome in the intensive care unit are sedated with the benzodiazepine midazolam. Midazolam undergoes extensive metabolism by CYP3A enzymes, which may be inhibited by hyperinflammation. Therefore, an exaggerated proinflammatory response, as often observed in COVID-19, may decrease midazolam clearance. To develop a population pharmacokinetic model for midazolam in adult intensive care unit patients infected with COVID-19 and to assess the effect of inflammation, reflected by IL-6, on the pharmacokinetics of midazolam. METHODS: Midazolam blood samples were collected once a week between March 31 and April 30 2020. Patients were excluded if they concomitantly received CYP3A4 inhibitors, CYP3A4 inducers and/or continuous renal replacement therapy. Midazolam and metabolites were analyzed with an ultra-performance liquid chromatography-tandem mass spectrometry method. A population pharmacokinetic model was developed, using nonlinear mixed effects modelling. IL-6 and CRP, markers of inflammation, were analyzed as covariates. RESULTS: The data were described by a one-compartment model for midazolam and the metabolites 1-OH-midazolam and 1-OH-midazolam-glucuronide. The population mean estimate for midazolam clearance was 6.7 L/h (4.8-8.5 L/h). Midazolam clearance was reduced by increased IL-6 and IL-6 explained more of the variability within our patients than CRP. The midazolam clearance was reduced by 24% (6.7-5.1 L/h) when IL-6 increases from population median 116 to 300 pg/mL. CONCLUSIONS: Inflammation, reflected by high IL-6, reduces midazolam clearance in critically ill patients with COVID-19. This knowledge may help avoid oversedation, but further research is warranted.

No common peroneal nerve palsies found after a peroneal nerve release prior to TKA in fixed valgus deformities (a retrospective cohort study).

PURPOSE: The main purpose of this study was to analyse the incidence of Common Peroneal Nerve Palsy (CPNP) after Total Knee Arthroplasty (TKA) for all alignments. Secondarily, the efficiency and safety of a Peroneal Nerve Release (PNR) prior to TKA in preoperative severe fixed valgus deformities were evaluated to prevent a CPNP. METHODS: Overall, 7612 TKAs were performed in the institution from 2009 to 2021. 1913 TKAs were performed by three surgeons, who consistently performed a PNR in case of a fixed valgus deformity of (1) more than 15°, or (2) more than 10° but in combination with a flexion contracture of more than 15°. Patients with fixed valgus deformities of more than 10° were identified (81 knees) and a comparison was made between the patients who received a PNR (26 knees) and those who did not receive a PNR (55 knees). Data for the analysis were collected from patient medical files and were compared with the Chi2-test or Fisher Exact test. RESULTS: A CPNP incidence of 0.2% (16/7612) was found after TKA for all alignments together. No CPNP cases (0%) were developed in the PNR-group, compared to five (9%) in the non-PNR group (p = NS). A larger preoperative valgus angle (17° vs 13°, p < 0.001) and flexion contracture (10° vs 3°, p < 0.001) was present in the PNR group compared with the non-PNR group. No PNR-related complications were reported. CONCLUSION: The CPNP incidence in this study is consistent with the previous literature. Furthermore, although not significant, the group that received a PNR procedure developed fewer CPNPs compared to the group without PNR. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Incidence and mortality of necrotizing fasciitis in The Netherlands: the impact of group A Streptococcus.

BACKGROUND: Little is known about the exact incidence of necrotizing soft tissue infections. The few incidences reported in international literature are not directly relatable to the Netherlands, or other European countries, due to geographic heterogeneity in causative micro-organisms involved. This resulted in the aim of this study to map the incidence, mortality rate and hospital course of necrotizing fasciitis infections in the Netherlands to gain insight in the incidence of necrotizing fasciitis in the Netherlands and the associated mortality and health care burden. METHODS: This nationwide retrospective database study used three distinct data sources to map the incidence of necrotizing fasciitis in the Netherlands between 2014 and 2019, being data from the Dutch Hospital Data (DHD) foundation, data from Osiris-AIZ, which is a database of notifiable diseases managed by regional Public Health Services (GGD) and the National Institute for Public Health and the Environment (RIVM), and previously published studies on necrotizing fasciitis conducted in the Netherlands. RESULTS: The incidence of necrotizing fasciitis in the Netherlands is estimated to be approximately 1.1 to 1.4 cases per 100,000 person years, which corresponds to 193-238 patients per year. Of all necrotizing fasciitis infections, 34 to 42% are caused by the group A Streptococcus. Annually, 56 patients die as a result of a necrotizing fasciitis infection (mortality of 23-29%) and 26 patients undergo an amputation for source control (11-14%). Patients stay a mean of 6 to 7 days at the intensive care unit and have a mean hospital length of stay of 24 to 30 days. CONCLUSION: The combination of nationwide databases provides reliable insight in the epidemiology of low-incidence and heterogenic diseases. In the Netherlands, necrotizing fasciitis is a rare disease with group A Streptococcus being the most common causative micro-organism of necrotizing fasciitis. The prior Dutch cohort studies on necrotizing fasciitis report slightly higher sample mortality rates, compared to the population mortality. However, necrotizing fasciitis remain associated with substantial morbidity and mortality, risk at amputation and health care burden characterized by prolonged ICU and hospital stay.

Dual-Use Quickscan: A Web-Based Tool to Assess the Dual-Use Potential of Life Science Research.

Research on pathogenic organisms is crucial for medical, biological and agricultural developments. However, biological agents as well as associated knowledge and techniques, can also be misused, for example for the development of biological weapons. Potential malicious use of well-intended research, referred to as "dual-use research", poses a threat to public health and the environment. There are various international resources providing frameworks to assess dual-use potential of the research concerned. However, concrete instructions for researchers on how to perform a dual-use risk assessment is largely lacking. The international need for practical dual-use monitoring and risk assessment instructions, in addition to the need to raise awareness among scientists about potential dual-use aspects of their research has been identified over the last years by the Netherlands Biosecurity Office, through consulting national and international biorisk stakeholders. We identified that Biorisk Management Advisors and researchers need a practical tool to facilitate a dual-use assessment on their specific research. Therefore, the Netherlands Biosecurity Office developed a web-based Dual-Use Quickscan (www.dualusequickscan.com), that can be used periodically by researchers working with microorganisms to assess potential dual-use risks of their research by answering a set of fifteen yes/no questions. The questions for the tool were extracted from existing international open resources, and categorized into three themes: characteristics of the biological agent, knowledge and technology about the biological agent, and consequences of misuse. The results of the Quickscan provide the researcher with an indication of the dual-use potential of the research and can be used as a basis for further discussions with a Biorisk Management Advisor. The Dual-Use Quickscan can be embedded in a broader system of biosafety and biosecurity that includes dual-use monitoring and awareness within organizations. Increased international attention to examine pathogens with pandemic potential has been enhanced by the current COVID-19 pandemic, hence monitoring of dual-use potential urgently needs to be encouraged.

Systematic approach towards establishing a National Inventory of Dangerous Pathogens.

International regulations stipulate that countries need to organize their biosafety and biosecurity systems to minimize the risk of accidental (biosafety) or malicious intentional (biosecurity) release of dangerous pathogens. International Health Regulations (IHR) benchmarks from the WHO state that even for a level of limited capacity countries need to 'Identify and document human and animal health facilities that store/maintain dangerous pathogens and toxins in the relevant sectors and health professionals responsible for them'. This study provides a stepwise, systematic approach and best practices for countries to initiate a national inventory of dangerous pathogens. With a national inventory of dangerous pathogens a country can identify and document information in a dedicated electronic database on institutes that store or maintain dangerous pathogens. The systematic approach for the implementation of a national inventory of dangerous pathogens consists of four stages; identification, preparation, implementation, and maintenance and evaluation. In the identification phase, commitment of the relevant national ministries is to be established, and a responsible government entity needs to be identified. In the preparatory phase, a list of pathogens to be incorporated in the inventory, as well as a list of institutes to include, is to be agreed upon. In the implementation phase, the institutes are contacted, and the collected data is stored safely and securely in a electronical database. Finally, in the maintenance and evaluation phase meaningful insights are derived and reported to the relevant government authorities. Also, preparations for updates and modifications are undertaken, such as modifications of pathogen lists or institute lists. The approach and database, which is available from the authors, have been tested for the implementation of a national inventory of dangerous pathogens in multiple East-African countries. A national inventory of dangerous pathogens helps countries in strengthening national biosafety and biosecurity as well as in their compliance to IHR.

CO-FLOW: COvid-19 Follow-up care paths and Long-term Outcomes Within the Dutch health care system: study protocol of a multicenter prospective cohort study following patients 2 years after hospital discharge.

BACKGROUND: First studies indicate that up to 6 months after hospital discharge, coronavirus disease 2019 (COVID-19) causes severe physical, cognitive, and psychological impairments, which may affect participation and health-related quality of life (HRQoL). After hospitalization for COVID-19, a number of patients are referred to medical rehabilitation centers or skilled nursing facilities for further treatment, while others go home with or without aftercare. The aftercare paths include 1] community-based rehabilitation; 2] in- and outpatient medical rehabilitation; 3] inpatient rehabilitation in skilled nursing facilities; and 4] sheltered care (inpatient). These aftercare paths and the trajectories of recovery after COVID-19 urgently need long-term in-depth evaluation to optimize and personalize treatment. CO-FLOW aims, by following the outcomes and aftercare paths of all COVID-19 patients after hospital discharge, to systematically study over a 2-year period: 1] trajectories of physical, cognitive, and psychological recovery; 2] patient flows, healthcare utilization, patient satisfaction with aftercare, and barriers/facilitators regarding aftercare as experienced by healthcare professionals; 3] effects of physical, cognitive, and psychological outcomes on participation and HRQoL; and 4] predictors for long-term recovery, health care utilization, and patient satisfaction with aftercare. METHODS: CO-FLOW is a multicenter prospective cohort study in the mid-west of the Netherlands with a 2-year follow-up period. Measurements comprise non-invasive clinical tests and patient reported outcome measures from a combined rehabilitation, pulmonary, and intensive care perspective. Measurements are performed at 3, 6, 12, and 24 months after hospital discharge and, if applicable, at rehabilitation discharge. CO-FLOW aims to include at least 500 patients who survived hospitalization for COVID-19, aged ≥18 years. DISCUSSION: CO-FLOW will provide in-depth knowledge on the long-term sequelae of COVID-19 and the quality of current aftercare paths for patients who survived hospitalization. This knowledge is a prerequisite to facilitate the right care in the right place for COVID-19 and comparable future infectious diseases. TRIAL REGISTRATION: The Netherlands Trial Register (NTR), https://www.trialregister.nl . Registered: 12-06-2020, CO-FLOW trialregister no. NL8710.