Assessing prescription of antibiotics after vaccination against pneumococcal pneumonia; using prescription sequence symmetry analysis.

OBJECTIVES: Prescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients. METHODS: We studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs. RESULTS: Amoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705-0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658-0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls. DISCUSSION: The lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption.

Remote Assistance for Home Care Workers: Concept and Technical Implementation at a Glance.

BACKGROUND: Long-term care faces severe challenges on the supply (shortages of formal and informal carers) as well as on the demand side (increasing number of care-dependent people). To cope with these challenges, new forms of support for the professional care network are needed. OBJECTIVES: This paper describes the concept and implementation of a Remote Care Assist (RCA) service, consisting of a web-application for the Care Expert Center (CXC) and Remote Support (RS) applications for the HoloLens 2 as well as for Android and iOS smartphones. METHODS: Using the evidence-based and user-centred innovation process (EUIP), a Remote Care Assist service was conceptualized and implemented for home care service settings in three European countries. RESULTS: After five iterations within two phases of the EUIP, the final feature set of the RCA-service was determined and implemented. CONCLUSION: By working closely with the target group, it was possible to identify potential hurdles and additional requirements such as a well-thought-out interaction concept for the HoloLens or a good organizational embedding of the service.

Coaching Robots for Older Seniors: Do They Get What They Expect? Insights from an Austrian Study.

To support the increasing number of older people, new (assistive) technologies are constantly being developed. For these technologies to be used successfully, future users need to be trained. Due to demographic change, this will become difficult in the future, as the resources for training will no longer be available. In this respect, coaching robots could have great potential to support younger seniors in particular. However, there is little evidence in the literature about the perceptions and potential impact of this technology on the well-being of older people. This paper provides insights into the use of a robot coach (robo-coach) to train younger seniors in the use of a new technology. The study was carried out in Austria in autumn 2020, involving 34 participants equally distributed among employees in their last three years of service and retirees in their first three years of retirement (23 female; 11 male). The aim was to assess participants' expectations and perceptions by examining the perceived ease of use and user experience of the robot in providing assistance during a learning session. The findings reveal a positive impression of the participants and promising results for using the robot as a coaching assistant in daily tasks.

Decellularization of Articular Cartilage: A Hydrochloric Acid-Based Strategy.

Removing cellular material from a tissue, a process called decellularization, reduces the risk of adverse host reactions, allows for efficient decontamination, and extends the shelf-life of the matrix. It facilitates the use of cartilage tissue as human-derived allograft, thus providing the field of cartilage regeneration with a biomaterial unmatched in its similarity to native cartilage in terms of structure, composition, and mechanical properties.The dense extracellular matrix of articular cartilage requires a particularly thorough process to achieve the removal of cells, cell debris, and reagents used in the process. In our studies (Nürnberger et al., EBioMedicine 64:103196, 2021; Schneider et al., Tissue Eng Part C Methods 22(12):1095-1107, 2016), we have successfully developed a protocol for achieving decellularization via physical, chemical, and enzymatic steps. Combining freeze-thaw cycles for devitalization, hydrochloric acid as decellularization agent and the enzymatic removal of glycosaminoglycans, results in an acellular scaffold that is fully biocompatible and promotes cellular attachment. The structure and sophisticated architecture of collagen type II is left intact.This chapter provides a comprehensive guide to the steps and reagents needed to decellularize articular cartilage. In addition to the standard decell-deGAG protocol, a fast option is given which is suitable for thin specimen. Histological evaluation is presented to illustrate treatment success.

Utilization of Drugs with Pharmacogenetic Dosing Recommendations in Switzerland: A Descriptive Study Using the Helsana Database.

Purpose: In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland. Methods: We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana). Results: Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes (CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MT-RNR1, and VKORC1) were responsible for over 95% of all potential drug-gene interactions. Conclusion: The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit.

[Peptic ulcer disease and H. pylori gastritis: key advances in clinical management]. / Gastroduodenale Ulkuskrankheit und Helicobacter pylori.

Helicobacter pylori (H. pylori) gastritis and non-steroidal anti-inflammatory drug (NSAID) intake are the most important risk factors for peptic ulcer disease (PUD) and ulcer bleeding. H. pylori infection was shown to increase the risk of ulcer bleeding in patients with PUD who are taking NSAID, aspirin, or another antiplatelet drug. H. pylori-positive patients on combined platelet aggregation inhibition are at the highest risk of bleeding. Evidence-based interdisciplinary treatment recommendations for the safe use of NSAID have been released. For patients with a moderate risk of PUD, the combination of NSAID and a proton pump inhibitor (PPI) or a monotherapy with a selective cyclooxygenase-2 (COX-2) inhibitor is recommended, whereas patients with a high risk of bleeding should receive a combination of a selective COX-2 inhibitor and a PPI. According to a recent randomized trial, hemodynamically stable patients with signs of upper gastrointestinal bleeding and an increased risk of death (Glasgow-Blatchford Score ≥ 12) undergoing endoscopy 6-24 after consultation do not have any disadvantage in terms of 30-day mortality compared to patients receiving endoscopy within 6 hours. After successful endoscopic hemostasis, additional prophylactic angiographic embolization does not reduce the risk of recurrent bleeding. Successful H. pylori eradication reduces the risk of developing gastric cancer (GC) in first-degree relatives of patients with GC by 73 %. In patients with successful endoscopic treatment of early GC, H. pylori testing with subsequent eradication also halves the rate of metachronous GC. Clarithromycin-based triple therapy for H. pylori eradication shows a decreasing effectiveness due to increasing antibiotic resistance, especially against macrolides. Accordingly, bismuth-containing quadruple therapy is widely recommended as the standard empiric first-line therapy.

Characterization of the deterioration of diabetes control in patients with a subsequent diagnosis of pancreatic cancer: A descriptive study.

BACKGROUND: Deterioration of diabetes control can be the first harbinger of pancreatic cancer. However, little is known about how to distinguish patients with pancreatic cancer-related diabetes deterioration from those with type 2 diabetes progression. We aimed to characterize the glycated hemoglobin (HbA1c) and body weight profile of pancreatic cancer patients with deteriorating diabetes before the cancer diagnosis. METHODS: Using data from the UK-based Clinical Practice Research Datalink (CPRD) GOLD, we established a study population including pancreatic cancer patients with diabetes deterioration in the >0.5-3 years before the cancer diagnosis and non-cancer patients with deterioration of type 2 diabetes (comparison group). Patients were considered to have diabetes deterioration if their glucose-lowering treatment was intensified. We characterized the longitudinal trajectories of HbA1c and body weight in pancreatic cancer patients compared with non-cancer patients before and after treatment intensification. RESULTS: The mean absolute increase in HbA1c from the pre-deterioration period, i.e. the time >1-2 years before treatment intensification, to the time of treatment intensification, was 1.5% ± 1.6% in pancreatic cancer patients vs. 0.9% ± 1.4% in non-cancer patients. After treatment intensification, mean HbA1c remained elevated in pancreatic cancer patients, while it returned to the pre-deterioration level in non-cancer patients. Body weight decreased by 1.9% ± 6.4% in cancer patients and increased by 0.3% ± 5.2% in non-cancer patients between the pre-deterioration period and treatment intensification, on average. CONCLUSIONS: Pancreatic cancer-related diabetes deterioration may frequently be characterized by pronounced increases in HbA1c, persistent elevation of HbA1c after treatment intensification, and concomitant weight loss.

Exploring the effectiveness of a fitness-app prototype for home care service users in Austria and Italy.

An infinite number of fitness apps are available on various app stores. However, hardly any of them are fitted to the needs and requirements of care-dependent people. This paper investigates the effectiveness of a customised fitness-app prototype for increasing physical activity in home care service users. Home care service users from Austria and Italy were randomly assigned to two groups. In total, 216 participants were involved in the field trial, 104 received a tablet with the fitness app and an activity tracker (treatment group), 112 did not (control group). Regularity of physical activity, frequency of fitness exercises and walking behaviour were self-reported by participants at baseline, after 4 months and after 8 months. In addition, the frequency of using the prototype was assessed based on the fitness app's logged usage data. We estimated multilevel mixed-effects ordered logistic models to examine the effects of the intervention. After 4 months, the intervention increased the home care users' probability of agreeing strongly with being physically active on a regular basis by 28 percentage points (p < 0.001; 95% CI: 0.20, 0.36) and their probability of reporting to exercise more than once a week by 45 percentage points (p < 0.001; 95% CI: 0.32, 0.57). Walking behaviour was not affected on group-level but improved for frequent users of the activity tracker. Frequent and regular users of the fitness app benefited most and effects persisted until the end of the 8 months controlled trial. Tailoring a fitness-app prototype to the needs of care-dependent people has the potential to support people with functional limitations to engage in a more active lifestyle. Future research is encouraged to seek further insights into how new technologies can support physical activities in people with long-term care needs.

User Requirements Analysis of an Embodied Conversational Agent for Coaching Older Adults to Choose Active and Healthy Ageing Behaviors during the Transition to Retirement: A Cross-National User Centered Design Study.

BACKGROUND: Retirement is recognized as a factor influencing the ageing process. Today, virtual health coaching systems can play a pivotal role in supporting older adults' active and healthy ageing. This study wants to answer two research questions: (1) What are the user requirements of a virtual coach (VC) based on an Embodied Conversational Agent (ECA) for motivating older adults in transition to retirement to adopt a healthy lifestyle? (2) How could a VC address the active and healthy ageing dimensions, even during COVID-19 times? METHODS: Two-wave focus-groups with 60 end-users aged 55 and over and 27 follow-up telephone interviews were carried out in Austria, Italy and the Netherlands in 2019-2020. Qualitative data were analysed by way of framework analysis. RESULTS: End-users suggest the VC should motivate older workers and retirees to practice physical activity, maintain social contacts and emotional well-being. The ECA should be reactive, customizable, expressive, sympathetic, not directive nor patronizing, with a pleasant and motivating language. The COVID-19 outbreak increased the users' need for functions boosting community relationships and promoting emotional well-being. CONCLUSIONS: the VC can address the active and healthy ageing paradigm by increasing the chances of doing low-cost healthy activities at any time and in any place.

Effects of an Information and Communication Technology-Based Fitness Program on Strength and Balance in Female Home Care Service Users.

There is evidence that training for strength and balance prevents decline in physical function in old age when the training is personally instructed. It is an open question whether interventions that deliver training via up-to-date technologies can achieve long-term effects. This study examined the effects of an 8-month fitness training program delivered via information and communication technology (ICT) on lower-body strength and balance in female home care users (n = 72) aged 75 years on average. For statistical analysis, the test group was divided into two subgroups, one who used the program at least 8 times per month (n = 26) and another one who used the program less often (n = 17) compared with a control group that received no exercise program (n = 29). It was found that regular ICT-exercisers exhibited positive effects over time on lower-body strength and balance compared to a decrease in both indicators in irregular exercisers and the control group. The authors see potential in offering exercise programs to people of advanced age via ICT to counteract physical decline in old age.

The Risk of Muscular Events Among New Users of Hydrophilic and Lipophilic Statins: an Observational Cohort Study.

BACKGROUND: Statins are effective lipid-lowering drugs for the prevention of cardiovascular disease, but muscular adverse events can limit their use. Hydrophilic statins (pravastatin, rosuvastatin) may cause less muscular events than lipophilic statins (e.g. simvastatin, atorvastatin) due to lower passive diffusion into muscle cells. OBJECTIVE: To compare the risk of muscular events between statins at comparable lipid-lowering doses and to evaluate if hydrophilic statins are associated with a lower muscular risk than lipophilic statins. DESIGN/SETTING: Propensity score-matched cohort study using data from the United Kingdom-based Clinical Practice Research Datalink (CPRD) GOLD. PATIENTS: New statin users. Cohort 1: pravastatin 20-40 mg (hydrophilic) vs simvastatin 10-20 mg (lipophilic), cohort 2: rosuvastatin 5-40 mg (hydrophilic) vs atorvastatin 10-80 mg (lipophilic), and cohort 3: simvastatin 40-80 mg vs atorvastatin 10-20 mg. MAIN MEASURES: The outcome was a first record of a muscular event (myopathy, myalgia, myositis, rhabdomyolysis) during a maximum follow-up of 1 year. KEY RESULTS: The propensity score-matched cohorts consisted of 1) 9,703, 2) 7,032, and 3) 37,743 pairs of statin users. Comparing the risk of muscular events between low-intensity pravastatin vs low-intensity simvastatin yielded a HR of 0.86 (95% CI 0.64-1.16). In the comparison of moderate- to high-intensity rosuvastatin vs equivalent doses of atorvastatin, we observed a HR of 1.17 (95% CI 0.88-1.56). Moderate- to high-intensity simvastatin was associated with a HR of 1.33 (95% CI 1.16-1.53), when compared with atorvastatin at equivalent doses. LIMITATIONS: We could not conduct other pairwise comparisons of statins due to small sample size. In the absence of a uniform definition on the comparability of statin doses, the applied dose ratios may not fully match with all literature sources. CONCLUSIONS: Our results do not suggest a systematically lower risk of muscular events for hydrophilic statins when compared to lipophilic statins at comparable lipid-lowering doses.

Effect of Diphenyleneiodonium Chloride on Intracellular Reactive Oxygen Species Metabolism with Emphasis on NADPH Oxidase and Mitochondria in Two Therapeutically Relevant Human Cell Types.

Reactive oxygen species (ROS) have recently been recognized as important signal transducers, particularly regulating proliferation and differentiation of cells. Diphenyleneiodonium (DPI) is known as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) and is also affecting mitochondrial function. The aim of this study was to investigate the effect of DPI on ROS metabolism and mitochondrial function in human amniotic membrane mesenchymal stromal cells (hAMSCs), human bone marrow mesenchymal stromal cells (hBMSCs), hBMSCs induced into osteoblast-like cells, and osteosarcoma cell line MG-63. Our data suggested a combination of a membrane potential sensitive fluorescent dye, tetramethylrhodamine methyl ester (TMRM), and a ROS-sensitive dye, CM-H2DCFDA, combined with a pretreatment with mitochondria-targeted ROS scavenger MitoTEMPO as a good tool to examine effects of DPI. We observed critical differences in ROS metabolism between hAMSCs, hBMSCs, osteoblast-like cells, and MG-63 cells, which were linked to energy metabolism. In cell types using predominantly glycolysis as the energy source, such as hAMSCs, DPI predominantly interacted with NOX, and it was not toxic for the cells. In hBMSCs, the ROS turnover was influenced by NOX activity rather than by the mitochondria. In cells with aerobic metabolism, such as MG 63, the mitochondria became an additional target for DPI, and these cells were prone to the toxic effects of DPI. In summary, our data suggest that undifferentiated cells rather than differentiated parenchymal cells should be considered as potential targets for DPI.

A Digital Health Coach for Younger Seniors - User Centred Requirements Collection.

BACKGROUND: Based on socio-economic and medical improvements as well as healthier lifestyles, a majority of baby boomer pensioners still feel fit and active and thus may struggle with transitioning into retirement. They could benefit from an ICT system to ease their transition into retirement and support general well- being. OBJECTIVES: The aim of this paper was to gain insights into the requirements for a digital coach to support their transition into retirement. METHODS: Two rounds of focus groups with older employees close to retirement, people just retired and relatives of retired were conducted. Outcomes were then identified through a framework analysis and integrated into the design of a digital coach. RESULTS: Four functional groups (i) physical activity, (ii) cognitive support, (iii) emotional support and (iv) social support were identified.

High-Resolution Analysis of Small Silver Clusters by Analytical Ultracentrifugation.

Although silver particles are used in various applications and a countless amount of synthesis routes exists, their formation mechanism is still poorly understood. Especially the first species formed directly after nucleation challenge analysis methods with their small size and transient nature. Analytical ultracentrifugation (AUC) has already proven to provide high size resolution and therefore enables the characterization of early nucleation species. Herein, we present an experiment of multiwavelength (MWL)-AUC of silver clusters, which revealed seven different cluster species. They consist of less than 10 atoms and therefore represent the first species formed after nucleation. Using MWL-AUC, UV/vis spectra could be allocated to each of them, which is shown for the first time. These findings establish MWL-AUC as a high-resolution tool to investigate a nucleation mechanism for silver and other metal nanoparticles.

Iodine-Enhanced Micro-CT Imaging of Soft Tissue on the Example of Peripheral Nerve Regeneration.

Microcomputed tomography (µCT) is widely used for the study of mineralized tissues, but a similar use for soft tissues is hindered by their low X-ray attenuation. This limitation can be overcome by the recent development of different staining techniques. Staining with Lugol's solution, a mixture of one part iodine and two parts potassium iodide in water, stands out among these techniques for its low complexity and cost. Currently, Lugol staining is mostly used for anatomical examination of tissues. In the present study, we seek to optimize the quality and reproducibility of the staining for ex vivo visualization of soft tissues in the context of a peripheral nerve regeneration model in the rat. We show that the staining result not only depends on the concentration of the staining solution but also on the amount of stain in relation to the tissue volume and composition, necessitating careful adaptation of the staining protocol to the respective specimen tissue. This optimization can be simplified by a stepwise staining which we show to yield a similar result compared to staining in a single step. Lugol staining solution results in concentration-dependent tissue shrinkage which can be minimized but not eliminated. We compared the shrinkage of tendon, nerve, skeletal muscle, heart, brain, and kidney with six iterations of Lugol staining. 60 ml of 0.3% Lugol's solution per cm3 of tissue for 24 h yielded good results on the example of a peripheral nerve regeneration model, and we were able to show that the regenerating nerve inside a silk fibroin tube can be visualized in 3D using this staining technique. This information helps in deciding the region of interest for histological imaging and provides a 3D context to histological findings. Correlating both imaging modalities has the potential to improve the understanding of the regenerative process.

Weight change and blood glucose concentration as markers for pancreatic cancer in subjects with new-onset diabetes mellitus: A matched case-control study.

OBJECTIVES: To evaluate the potential of blood glucose levels and weight change before the onset of diabetes as predictors of pancreatic cancer among subjects with new-onset diabetes, that is, cancer-related diabetes versus normal type 2 diabetes. METHODS: We conducted a case-control study among subjects with new diabetes in the United Kingdom-based Clinical Practice Research Datalink. Cases were pancreatic cancer subjects with diabetes for ≤2 years before the cancer diagnosis (i.e., cancer-related diabetes). Controls were cancer-free, type 2 diabetic subjects matched to cases on age, sex, and diabetes duration. We calculated adjusted odds ratios (aORs) for pancreatic cancer as a function of both weight change and blood glucose before the onset of diabetes. RESULTS: Weight loss of 10.0%-14.9% at diabetes onset was associated with an aOR for pancreatic cancer of 3.58 (95% CI 2.31-5.54), loss of ≥15.0%, with an aOR of 4.56 (95% CI 2.82-7.36), compared with stable weight. Blood glucose levels of ≤5.1 mmol/L or 5.2-5.6 mmol/L before diabetes onset were associated with an increased risk of a pancreatic cancer diagnosis, with aORs of 2.42 (95% CI 1.60-3.66) and 2.20 (95% CI 1.45-3.35), respectively, when compared with blood glucose levels ≥6.3 mmol/L within >2-3 years before cancer detection. CONCLUSIONS: Weight loss as well as blood glucose levels in the normal range (and thus rapid development of hyperglycemia) before diabetes onset may be predictive of pancreatic cancer-related diabetes and may help target which subjects with new diabetes to refer for pancreatic cancer screening examinations.

Dental care behaviour in Switzerland

Improvements in oral health are changing the requirements for oral health care provision. This study assessed the frequency and major reason of dental visits and personal oral hygiene measures in Switzerland, and temporal trends in visit frequency. The number of dental visits in the previous twelve months, the reason for these visits, and the prevalence of oral hygiene measures were quantified from weighted data from the 2012 Swiss Health Survey. The frequency of dental visits in 2012 was compared with previous surveys (1992­2007). Almost two thirds of subjects reported visiting a dentist and almost half had visited a dental hygienist in the previous twelve months. Voluntary (33%) or recall check-ups (25%) were the most common reasons for the last dental visit across age groups. Treatment needs including caries/filling/endodontic treatment (10%), crowns/FDP/RDP/implants (8%), toothache (5%), extraction (5%), periodontal complaints (2%), or orthodontic appliances (2%) were more heterogeneously distributed across age groups. One in ten subjects had dental implants; prevalence increased with increasing age as did the number of missing teeth. Use of interdental cleaning devices and frequent tooth brushing were more common among subjects with few or no missing teeth and among subjects with higher versus lower income or education. Oral health awareness varied with a higher awareness in women than in men and in subjects with higher versus lower income or education. The prevalence of dental implants and dental hygienist's visits has increased in Switzerland since 2002, but oral hygiene measures remained stable.

Association Between Glycemic Control and Risk of Fracture in Diabetic Patients: A Nested Case-Control Study.

CONTEXT: Diabetes mellitus (DM) has been associated with an increased risk of fractures. However, the effect of glycemic control on the risk of fracture is not well understood. OBJECTIVE: To evaluate the association between glycemic control and the risk of low-trauma fractures in patients with type 1 DM (T1DM) and type 2 DM (T2DM). DESIGN: Nested case-control analysis. SETTING: UK-based Clinical Practice Research Datalink. PATIENTS OR OTHER PARTICIPANTS: The study population was patients whose T1DM or T2DM had been newly diagnosed between 1995 and 2015. The cases were patients with a low-trauma fracture after DM onset. We matched four controls to each case by age, sex, general practice, fracture date, and DM type and duration. STATISTICAL ANALYSIS: Conditional logistic regression analyses were performed, adjusted for covariates, including body mass index, smoking, DM complications and medications. RESULTS: The study population included 3329 patients with T1DM and 44,275 patients with T2DM. The median duration between DM onset and fracture date was 4.5 years for both T1DM and T2DM. The risk of fracture was increased in the patients with T1DM with a mean hemoglobin A1c >8.0% (adjusted OR, 1.39; 95% CI, 1.06 to 1.83) compared with those patients with T1DM and a mean hemoglobin A1c ≤7.0%. No such effect was found in the patients with T2DM. Independently of glycemic control, the risk of fracture was elevated in patients with T2DM and the current use of rosiglitazone and pioglitazone. CONCLUSIONS: The effect of glycemic control on the risk of low-trauma fracture differs between patients with T1DM and T2DM. Poor glycemic control increased the risk of fractures in patients with T1DM but not in those with T2DM.

Traditional and Digital Biomarkers: Two Worlds Apart?

The identification and application of biomarkers in the clinical and medical fields has an enormous impact on society. The increase of digital devices and the rise in popularity of health-related mobile apps has produced a new trove of biomarkers in large, diverse, and complex data. However, the unclear definition of digital biomarkers, population groups, and their intersection with traditional biomarkers hinders their discovery and validation. We have identified current issues in the field of digital biomarkers and put forth suggestions to address them during the DayOne Workshop with participants from academia and industry. We have found similarities and differences between traditional and digital biomarkers in order to synchronize semantics, define unique features, review current regulatory procedures, and describe novel applications that enable precision medicine.

Band Sedimentation Experiment in Analytical Ultracentrifugation Revisited.

The band sedimentation experiment in analytical ultracentrifugation (AUC) allows for the performance of a chemical reaction inside the AUC and also offers separation of individual pure components in a sedimentation velocity experiment. Although this experiment offers exciting possibilities for application, it is barely used. This is related to the bad definition of the initial conditions. Both the duration and the time of the solution overlay during rotor acceleration are not known. In this study, we investigate these conditions under the variation of the overlay volume using recording of interference patterns in a continuous mode during the acceleration of the rotor. It was found that the overlay occurs at rotor speeds between 770 and 2000 rpm, which is very low compared to typical experimental rotor speeds from 3 000 to 60 000 rpm and therefore elucidates that the generated reaction products, respectively, overlaid species are subject to the centrifugal force almost from the beginning. Also, the duration of the overlay is less than 1.2 s, which is very fast compared to hours of centrifugation time for an experiment and we demonstrated that the overlay compartment is completely emptied during overlay allowing for the precise calculation of the meniscus using the known sample sector geometry. Our results show that the initial conditions of the experiment are defined and should make an adapted analysis possible if the interdiffusion of the two solvents is taken into account, which lead to a dynamic density gradient.