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Anne L Meulenbroek,1 Miriam C Faes,2 Stefanie R van Mil,1 MG Buimer,1 Hans GW de Groot,1 Eelco J Veen,1 Gwan H Ho,1 Leandra JM Boonman-de Winter,3,4 Jolanda de Vries,5,6 Rebecca van Gorkom,1 Fleur Toonders,1 Rene van Alphen,7 Karolien van Overveld,8 Nathalie Verbogt,1 Ewout W Steyerberg,9 Lijckle van der Laan1,10 1Department of Surgery, Amphia Hospital, Breda, the Netherlands; 2Department of Geriatrics, Amphia Hospital, Breda, the Netherlands; 3Department of Scientific Research, Amphia Hospital, Breda, the Netherlands; 4Admiraal de Ruyter Ziekenhuis, Goes, the Netherlands; 5Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands; 6Board, Admiraal de Ruyter Hospital, Goes, the Netherlands; 7Department of Physical Therapy, Amphia Hospital, Breda, the Netherlands; 8Department of Dieticians, Amphia Hospital, Breda, the Netherlands; 9Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, the Netherlands; 10Department of Cardiovascular Science, University Hospitals Leuven, Leuven, BelgiumCorrespondence: Anne L Meulenbroek, Department of Surgery, Amphia Hospital, Molengracht 21, Breda, 4818 CK, the Netherlands, Tel +31 76 595 3157, Fax +31 76 595 3818, Email AMeulenbroek1@amphia.nlObjective: Chronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥ 65 years.Design: A prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program.Methods: Chronic limb threatening ischemia patients ≥ 65 years that require revascularization will participate in the program. This program focuses on optimizing the patient’s overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group.Discussion: This study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient’s preoperative mental and physical condition to prevent postoperative complications, including delirium.Trial: This protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.Keywords: chronic limb threatening ischemia, vascular surgical procedures, delirium, delirium/prevention and control, prehabilitation

Building on a plethora of conjectured emendations for IOϒΔAIAN, this article approaches the issue once again to test the viability of a quantitative tool and to establish the possibility of palaeographical confusion of IOϒΔAIAN with an alternative topo- or demonym. The article starts with an experiment using Greek topo- and demonyms derived from contemporary Christian, Jewish, and Classical sources to establish a palaeographical confusion score. Next the likeliness of the “closest” alternatives in the geographical arrangement of Acts 2:9–11 is explored. The article ends with an evaluation of the possible implications for the text in Acts 2:9 as well as a critical appraisal of the method for conjectural criticism.

Sandra AS van den Heuvel,1 Selina EI van der Wal,1 Ewald M Bronkhorst,2 Michiel C Warlé,3 May Ronday,4 Judith Plat,4 Nens van Alfen,5 Leo AB Joosten,6 Jos GC Lerou,1 Kris CP Vissers,1 Monique AH Steegers7 1Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands; 2Department of Health Evidence, Radboud University Medical Centre, Nijmegen, the Netherlands; 3Division of Vascular and Transplant Surgery, Department of Surgery, Radboud University Medical Centre, Nijmegen, the Netherlands; 4Department of Anesthesiology, Alexander Monro Breast Cancer Hospital, Bilthoven, the Netherlands; 5Donders Institute for Brain Cognition and Behavior, Department of Neurology, Radboud University Medical Centre, Nijmegen, the Netherlands; 6Department of Internal Medicine and Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, the Netherlands; 7Department of Anesthesiology, Pain and Palliative Medicine, Amsterdam University Medical Centre, Amsterdam, the NetherlandsCorrespondence: Sandra AS van den HeuvelDepartment of Anesthesiology, Pain and Palliative Medicine, Radboud University Nijmegen Medical Center, Internal mail 630, P.O. Box 9101, Nijmegen 6525 GA, the NetherlandsTel +31 243615244Email Sandra.vandenHeuvel@radboudumc.nlPurpose: An imbalance in perioperative cytokine response may cause acute pain and postoperative complications. Anesthetic drugs modulate this cytokine response, but their role in non-major breast cancer surgery is unclear. In an exploratory study, we investigated whether intravenous lidocaine and dexamethasone could modulate the cytokine response into an anti-inflammatory direction. We also evaluated interrelationships between cytokine levels, pain scores and postoperative complications. Our goal is to develop multimodal analgesia regimens optimizing outcome after breast cancer surgery.Patients and Methods: Forty-eight patients undergoing a lumpectomy were randomly assigned to placebo or lidocaine (1.5 mg⋅kg− 1 followed by 2 mg⋅kg− 1⋅hour− 1) supplemented by dexamethasone zero, 4 or 8 mg, yielding six groups of eight patients. Interleukin (IL)-1β, IL-1Ra, IL-6, IL-10 levels and pain scores were measured at baseline and four hours postoperatively. We assessed postoperative complications occurring within 30 days. We noted persistent pain and infections as potential immune-related complications (PIRC). We used multiple regression to disentangle the effects of the individual study drugs (given by their partial regression coefficients (b)). Odds ratios (OR) estimated the link between pain scores and complications.Results: Dexamethasone 8 mg increased IL-10 (b=12.70 (95% CI=8.06– 17.34), P< 0.001). Dexamethasone 4 mg and 8 mg decreased the ratio IL-6/IL-10 (b=− 2.60 (− 3.93 to − 1.26), P< 0.001 and b=− 3.59 (− 5.04 to − 2.13), P< 0.001, respectively). We could not show modulatory effects of lidocaine on cytokines. High pain scores were linked to the occurrence of PIRC’s (OR=2.028 (1.134– 3.628), P=0.017). Cytokine levels were not related either to acute pain or PIRC.Conclusion: Dexamethasone modulated the perioperative cytokine response into an anti-inflammatory direction. An overall lidocaine effect was not found. Patients with higher pain scores suffered from more 30-day PIRCs. Cytokine levels were not associated with pain or more postoperative complications, even not with PIRC. Larger studies in breast cancer surgery are needed to confirm these explorative results.Keywords: acute pain, anesthetic agents, immune response, lumpectomy, perioperative outcomes

Before the interpretation of any text can start, the original wording of the text itself must be critically established. Conventionally, this is done following qualitative criteria. This article, however, explores the application of spatial analyses to New Testament textual criticism by demonstrating how the Levenshtein edit distance could be adapted to calculate confusion distances for variant readings in New Testament manuscripts, i.e. the possibility that a (combination of) letter(s) is confused by another (combination of) letter(s). Subsequently the outcomes are translated to Euclidian space using classical Multi-Dimensional Scaling, which enables visualisation and spatial analyses (in this case not related to geographical space). The article focuses on the data preparation and algorithm to make the data suitable for spatial analyses, thus providing the New Testament textual critic with new analytical tools.

BackgroundHealth behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are leading risk factors for noncommunicable chronic diseases and play a central role in limiting health and life satisfaction. To date, however, health behaviors tend to be considered separately from one another, resulting in guidelines and interventions for healthy aging siloed by specific behaviors and often focused only on a given health behavior without considering the co-occurrence of family, social, work, and other behaviors of everyday life. ObjectiveThe aim of this study is to understand how behaviors cluster and how such clusters are associated with physical and mental health, life satisfaction, and health care utilization may provide opportunities to leverage this co-occurrence to develop and evaluate interventions to promote multiple health behavior changes. MethodsUsing cross-sectional baseline data from the Canadian Longitudinal Study on Aging, we will perform a predefined set of exploratory and hypothesis-generating analyses to examine the co-occurrence of health and everyday life behaviors. We will use agglomerative hierarchical cluster analysis to cluster individuals based on their behavioral tendencies. Multinomial logistic regression will then be used to model the relationships between clusters and demographic indicators, health care utilization, and general health and life satisfaction, and assess whether sex and age moderate these relationships. In addition, we will conduct network community detection analysis using the clique percolation algorithm to detect overlapping communities of behaviors based on the strength of relationships between variables. ResultsBaseline data for the Canadian Longitudinal Study on Aging were collected from 51,338 participants aged between 45 and 85 years. Data were collected between 2010 and 2015. Secondary data analysis for this project was approved by the Ottawa Health Science Network Research Ethics Board (protocol ID #20190506-01H). ConclusionsThis study will help to inform the development of interventions tailored to subpopulations of adults (eg, physically inactive smokers) defined by the multiple behaviors that describe their everyday life experiences. International Registered Report Identifier (IRRID)DERR1-10.2196/24887

BackgroundAtrial fibrillation (AF), sternal wound infection, and cardiac decompensation are complications that can occur after cardiac surgery. Early detection of these complications is clinically relevant, as early treatment is associated with better clinical outcomes. Remote monitoring with the use of a smartphone (mobile health [mHealth]) might improve the early detection of complications after cardiac surgery. ObjectiveThe primary aim of this study is to compare the detection rate of AF diagnosed with an mHealth solution to the detection rate of AF diagnosed with standard care. Secondary objectives include detection of sternal wound infection and cardiac decompensation, as well as assessment of quality of life, patient satisfaction, and cost-effectiveness. MethodsThe Box 2.0 is a study with a prospective intervention group and a historical control group for comparison. Patients undergoing cardiac surgery at Leiden University Medical Center are eligible for enrollment. In this study, 365 historical patients will be used as controls and 365 other participants will be asked to receive either The Box 2.0 intervention consisting of seven home measurement devices along with a video consultation 2 weeks after discharge or standard cardiac care for 3 months. Patient information will be analyzed according to the intention-to-treat principle. The Box 2.0 devices include a blood pressure monitor, thermometer, weight scale, step count watch, single-lead electrocardiogram (ECG) device, 12-lead ECG device, and pulse oximeter. ResultsThe study started in November 2018. The primary outcome of this study is the detection rate of AF in both groups. Quality of life is measured with the five-level EuroQol five-dimension (EQ-5D-5L) questionnaire. Cost-effectiveness is calculated from a society perspective using prices from Dutch costing guidelines and quality of life data from the study. In the historical cohort, 93.9% (336/358) completed the EQ-5D-5L and patient satisfaction questionnaires 3 months after cardiac surgery. ConclusionsThe rationale and design of a study to investigate mHealth devices in postoperative cardiac surgery patients are presented. The first results are expected in September 2020. Trial RegistrationClinicalTrials.gov NCT03690492; http://clinicaltrials.gov/show/NCT03690492 International Registered Report Identifier (IRRID)DERR1-10.2196/16326

The driving force behind our internet economy is demand-side economies of scale, also known as network effects. These arise when users create value for other users and are enhanced by technologies that create efficiencies in social networking. While resource control and supply side efficiency used to be key success factors in the past, building platforms, orchestrating networks and managing relationships determine success in an increasingly digital world. Successful platforms seek to maximize the overall value of the whole system in a circular, revolving and feedback-driven process. By attracting more platform participants they are able to offer a higher value. The larger the network, the better the matches between supply and demand and the richer the data that can be used to find matches. Successful platforms put companies that use traditional business models at risk. Many companies are still highly competitive, but when platforms enter the same marketplace, the platforms usually win. Companies that fail to create platforms on their own or to integrate their business into existing platforms will be unable to compete for long.

BackgroundImmigrants to Canada belonging to ethnocultural minority groups are at increased risk of developing diabetes and complications, including diabetic retinopathy, and they are also less likely to be screened and treated. Improved attendance to retinopathy screening (eye tests) has the potential to reduce permanent complications, including blindness. ObjectiveThis study aims to identify the barriers and enablers of attending diabetic retinopathy screening among ethnocultural minority immigrants living with diabetes in Quebec and Ontario, Canada, to inform the development of a behavior change intervention to improve diabetic retinopathy screening attendance. MethodsThe research question draws on the needs of patients and clinicians. Using an integrated knowledge translation approach, the research team includes clinicians, researchers, and patient partners who will contribute throughout the study to developing and reviewing materials and procedures, helping to recruit participants, and disseminating findings. Using a convenience snowball strategy, we will recruit participants from three target groups: South Asian and Chinese people, and French-speaking people of African descent. To better facilitate reaching these groups and support participant recruitment, we will partner with community organizations and clinics serving our target populations in Ontario and Quebec. Data will be collected using semistructured interviews, using topic guides developed in English and translated into French, Mandarin, Hindi, and Urdu, and conducted in those languages. Data collection and analysis will be structured according to the Theoretical Domains Framework (TDF), which synthesizes predominant theories of behavior change into 14 domains covering key modifiable factors that may operate as barriers or enablers to attending eye screening. We will use directed content analysis to code barriers and enablers to TDF domains, then thematic analysis to define key themes within domains. ResultsThis study was approved for funding in December 2017, and the research ethics board approved the conduct of the study as of January 13, 2018. Data collection then began in April 2018. As of August 28, 2018, we have recruited 22 participants, and analysis is ongoing, with results expected to be published in 2020. ConclusionsFindings from this study will inform the codevelopment of theory-informed, culturally- and linguistically-tailored interventions to support patients in attending retinopathy screening. International Registered Report Identifier (IRRID)DERR1-10.2196/15109