Evaluation of Eligibility Criteria Relevance for the Purpose of IT-Supported Trial Recruitment: Descriptive Quantitative Analysis.

BACKGROUND: Clinical trials (CTs) are crucial for medical research; however, they frequently fall short of the requisite number of participants who meet all eligibility criteria (EC). A clinical trial recruitment support system (CTRSS) is developed to help identify potential participants by performing a search on a specific data pool. The accuracy of the search results is directly related to the quality of the data used for comparison. Data accessibility can present challenges, making it crucial to identify the necessary data for a CTRSS to query. Prior research has examined the data elements frequently used in CT EC but has not evaluated which criteria are actually used to search for participants. Although all EC must be met to enroll a person in a CT, not all criteria have the same importance when searching for potential participants in an existing data pool, such as an electronic health record, because some of the criteria are only relevant at the time of enrollment. OBJECTIVE: In this study, we investigated which groups of data elements are relevant in practice for finding suitable participants and whether there are typical elements that are not relevant and can therefore be omitted. METHODS: We asked trial experts and CTRSS developers to first categorize the EC of their CTs according to data element groups and then to classify them into 1 of 3 categories: necessary, complementary, and irrelevant. In addition, the experts assessed whether a criterion was documented (on paper or digitally) or whether it was information known only to the treating physicians or patients. RESULTS: We reviewed 82 CTs with 1132 unique EC. Of these 1132 EC, 350 (30.9%) were considered necessary, 224 (19.8%) complementary, and 341 (30.1%) total irrelevant. To identify the most relevant data elements, we introduced the data element relevance index (DERI). This describes the percentage of studies in which the corresponding data element occurs and is also classified as necessary or supplementary. We found that the query of "diagnosis" was relevant for finding participants in 79 (96.3%) of the CTs. This group was followed by "date of birth/age" with a DERI of 85.4% (n=70) and "procedure" with a DERI of 35.4% (n=29). CONCLUSIONS: The distribution of data element groups in CTs has been heterogeneously described in previous works. Therefore, we recommend identifying the percentage of CTs in which data element groups can be found as a more reliable way to determine the relevance of EC. Only necessary and complementary criteria should be included in this DERI.

Implementation of inclusion and exclusion criteria in clinical studies in OHDSI ATLAS software.

Clinical trials are essential parts of a medical study process, but studies are often cancelled due to a lack of participants. Clinical Trial Recruitment Support Systems are systems that help to increase the number of participants by seeking more suitable subjects. The software ATLAS (developed by Observational Health Data Sciences and Informatics) can support the launch of a clinical trial by building cohorts of patients who fulfill certain criteria. The correct use of medical classification systems aiming at clearly defined inclusion and exclusion criteria in the studies is an important pillar of this software. The aim of this investigation was to determine whether ATLAS can be used in a Clinical Trial Recruitment Support System to portray the eligibility criteria of clinical studies. Our analysis considered the number of criteria feasible for integration with ATLAS and identified its strengths and weaknesses. Additionally, we investigated whether nonrepresentable criteria were associated with the utilized terminology systems. We analyzed ATLAS using 223 objective eligibility criteria from 30 randomly selected trials conducted in the last 10 years. In the next step, we selected appropriate ICD, OPS, LOINC, or ATC codes to feed the software. We classified each criterion and study based on its implementation capability in the software, ensuring a clear and logical progression of information. Based on our observations, 51% of the analyzed inclusion criteria were fully implemented in ATLAS. Within our selected example set, 10% of the studies were classified as fully portrayable, and 73% were portrayed to some extent. Additionally, we conducted an evaluation of the software regarding its technical limitations and interaction with medical classification systems. To improve and expand the scope of criteria within a cohort definition in a practical setting, it is recommended to work closely with personnel involved in the study to define the criteria precisely and to carefully select terminology systems. The chosen criteria should be combined according to the specific setting. Additional work is needed to specify the significance and amount of the extracted criteria.

Fluctuations in Oxygen Saturation during Synchronized Nasal Intermittent Positive Pressure Ventilation and Nasal High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants: A Randomized Crossover Trial.

BACKGROUND: Very low birth weight (VLBW) infants on noninvasive ventilation (NIV) experience frequent fluctuations in oxygen saturation (SpO2) that are associated with an increased risk for mortality and severe morbidities. METHODS: In this randomized crossover trial, VLBW infants (n = 22) born 22+3 to 28+0 weeks on NIV with supplemental oxygen were allocated on two consecutive days in random order to synchronized nasal intermittent positive pressure ventilation (sNIPPV) and nasal high-frequency oscillatory ventilation (nHFOV) for 8 h. nHFOV and sNIPPV were set to equivalent mean airway pressure and transcutaneous pCO2. Primary outcome was the time spent within the SpO2 target (88-95%). RESULTS: During sNIPPV, VLBW infants spent significantly more time within the SpO2 target (59.9%) than during nHFOV (54.6%). The proportion of time spent in hypoxemia (22.3% vs. 27.1%) and the mean fraction of supplemental oxygen (FiO2) (29.4% vs. 32.8%) were significantly reduced during sNIPPV, while the respiratory rate (50.1 vs. 42.6) was significantly higher. Mean SpO2, SpO2 above the target, number of prolonged (>1 min) and severe (SpO2 <80%) hypoxemic episodes, parameters of cerebral tissue oxygenation using NIRS, number of FiO2 adjustments, heart rate, number of bradycardias, abdominal distension and transcutaneous pCO2 did not differ between both interventions. CONCLUSIONS: In VLBW infants with frequent fluctuations in SpO2, sNIPPV is more efficient than nHFOV to retain the SpO2 target and to reduce FiO2 exposure. These results demand more detailed investigations into cumulative oxygen toxicities during different modes of NIV over the weaning period, particularly with regard to consequences for long-term outcomes.

Interventional Treatment of Recurrent Ventricular Septal Defect Planed by 3D-Printed Reconstruction of the Heart.

We report a complex case of a 53-year-old male patient with recurrent ischemic ventricular septal defect that had been occluded by a surgical patch. Treatment was accomplished utilizing a 3-dimensional-printed model for preprocedural planning. In the future, printing of 3-dimensional models could offer new therapeutic strategies on an individual level. (Level of Difficulty: Intermediate.).

[Why you should know the "nose cycle" as a pneumologist and sleep medicine specialist]. / Warum man auch als Pneumologe und Schlafmediziner den "Nasenzyklus" kennen sollte.

The nasal cycle refers to the anticyclic swelling and decongestion of the two nasal cavities that occur during the day and during sleep, while the overall nasal flow remains constant. The nasal cycle was first described by R. Kayser in 1895. Each cycle consists of a working phase and a subsequent resting phase, the purpose of which is the rehydration and regeneration of the mucosa. A nasal cycle occurs in about 70-90% of people. The duration of the phase is affected by age, body position, physical activity, mucociliary clearance and time of day. Typically, the cycle lengthens during sleep. Long-term rhinoflowmetry enables assessment of the circadian course of the alternating cyclic changes of the nasal mucosa.

Significant advantages for first line treatment with TNF-alpha inhibitors in pediatric patients with inflammatory bowel disease - Data from the multicenter CEDATA-GPGE registry study.

Background and aims: In recent years, biological agents, such as anti-TNF-α blockers, have been introduced and have shown efficacy in pediatric patients with inflammatory bowel disease (IBD). Here, the prescription mode differentiated into a first/second line application, and efficacy and side effects are evaluated beginning from 2004 until today. Methods: Statistical analyses of the prospective and ongoing CEDATA multicenter registry data from the Society of Pediatric Gastroenterology and Nutrition (GPGE) were performed for patients receiving a biological agent at least once during the period from June 2004 until November 2020 (n = 487). The analyzed parameters were patient demographics, disease extent and behavior, prior or concurrent therapies, duration and outcome of biological therapy, disease-associated complications, drug-related complications, laboratory parameters and treatment response as determined by the Physician's Global Assessment. Results: Crohn's disease (CD) was present in 71.5% of patients, and 52% were boys. Patients showed high disease activity when receiving a first-line TNF-α blocker. After 2016, patients who failed to respond to anti-TNF-α induction therapy were treated with off-label biologics (vedolizumab 4.3% and ustekinumab 2.1%). Propensity score matching indicated that patients with CD and higher disease activity benefitted significantly more from early anti-TNF-α therapy. This assessment was based on a clinical evaluation and lab parameters related to inflammation compared to delayed second-line treatment. Additionally, first-line treatment resulted in less treatment failure and fewer extraintestinal manifestations during TNF-α blockade. Conclusion: First-line treatment with anti-TNF-α drugs is effective and safe. An earlier start significantly reduces the risk of treatment failure and is associated with fewer extraintestinal manifestations during longitudinal follow-up.

Evaluation of a Regulatory Orientation Guide for Young Entrepreneurs in the Field of Digital Health.

BACKGROUND: The number of software products in the field of health and medicine increases excessively. Self-tracking, fitness, dose calculation, and analysis of physiological data - apps are popular and commonly used. For young entrepreneurs, it is difficult to recognize and understand the distinction between software as medical product and health software products. A product-related orientation guide was developed to help start-ups to understand the difference and to find the right strategy for placing their product on the market. OBJECTIVES: An initial evaluation of this orientation guide to improve the comprehensibility, the simplicity, and to validate the benefit. METHODS: The evaluation was performed using a questionnaire. In total, 15 employees from start-ups or those in foundation phase and in regulatory affairs positions or comparable were interviewed. RESULTS: the orientation guide was rated as very helpful and comprehensible. 80 % would highly recommend it to others. CONCLUSION: The orientation guide was positively evaluated and can be used in field. Nevertheless, further investigations must be performed, and a post-market surveillance will be necessary.

Development of a Multidimensional Assessment Tool for the Evaluation of Holistic Quality of Life in Parkinson's Disease.

BACKGROUND: Parkinsonian syndromes are heterogeneous chronic neurodegenerative disorders associated with both motor and non-motor symptoms. The symptoms have major psychosocial effects on the quality of life of patients and can be a burden for caregivers. So far, several questionnaires have been developed to assess quality of life in Parkinsonism, but none of these include the positive sides on well-being such as personal and social resilience factors. OBJECTIVE: The aim of this study is to develop a digital framework for a longitudinal assessment of quality of life during the progression of Parkinson's disease. METHODS: The CHAPO model (Challenges and Potentials) has been established in a vast study by Wagner et al. to assess the quality of life of older people. This model includes environmental and individual factors, life chances, and life results, such as individual life evaluation, from a subjective as well as an objective point of view. Therefore, it has been adapted in several development steps to include the specific aspects that affect quality of life in Parkinsonian syndromes. The development process included 6 steps: definition, refinement, operationalization, piloting/debriefing, adjustment, and integration. RESULTS: The development of the CHAPO-PD model has been completed and it represents the first main result of this study. CONCLUSION: By taking a holistic understanding of quality of life into account, we expect to detect previously unrecognized factors, which correlate to the subjective well-being of Parkinson's disease patients, and aim to use these findings to improve the health care structures for patients with Parkinson's disease and related disorders.

Pilot study on nocturnal monitoring of crackles in children with pneumonia.

BACKGROUND: The clinical diagnosis of pneumonia is usually based on crackles at auscultation, but it is not yet clear what kind of crackles are the characteristic features of pneumonia in children. Lung sound monitoring can be used as a "longtime stethoscope". Therefore, it was the aim of this pilot study to use a lung sound monitor system to detect crackles and to differentiate between fine and coarse crackles in children with acute pneumonia. The change of crackles during the course of the disease shall be investigated in a follow-up study. PATIENTS AND METHODS: Crackles were recorded overnight from 22:00 to 06:00 h in 30 children with radiographically confirmed pneumonia. The data for a total of 28 800 recorded 30-s epochs were audiovisually analysed for fine and coarse crackles. RESULTS: Fine crackles and coarse crackles were recognised in every patient with pneumonia, but the number of epochs with and without crackles varied widely among the different patients: fine crackles were detected in 40±22% (mean±sd), coarse crackles in 76±20%. The predominant localisation of crackles as recorded during overnight monitoring was in accordance with the radiographic infiltrates and the classical auscultation in most patients. The distribution of crackles was fairly equal throughout the night. However, there were time periods without any crackle in the single patients so that the diagnosis of pneumonia might be missed at sporadic auscultation. CONCLUSION: Nocturnal monitoring can be beneficial to reliably detect fine and coarse crackles in children with pneumonia.

Confirmation of Calcium Phosphate Cement Biodegradation after Jawbone Augmentation around Dental Implants Using Three-Dimensional Visualization and Segmentation Software.

The use of autologous bone graft for oral rehabilitation of bone atrophy is considered the gold standard. However, the available grafts do not allow a fast loading of dental implants, as they require a long healing time before full functionality. Innovative bioactive materials provide an easy-to-use solution to this problem. The current study shows the feasibility of calcium phosphate cement paste (Paste-CPC) in the sinus. Long implants were placed simultaneously with the cement paste, and provisional prosthetics were also mounted in the same sessions. Final prosthetics and the full loading took place within the same week. Furthermore, the study shows for the first time the possibility to monitor not only healing progression using Cone Beam Computer tomography (CBCT) but also material retention, over two years, on a case study example. The segmented images showed a 30% reduction of the cement size and an increased mineralized tissue in the sinus. Mechanical testing was performed qualitatively using reverse torque after insertion and cement solidification to indicate clinical feasibility. Both functional and esthetic satisfaction remain unchanged after one year. This flowable paste encourages the augmentation procedure with less invasive measure through socket of removed implants. However, this limitation can be addressed in future studies.

Automatic detection and monitoring of abnormal skull shape in children with deformational plagiocephaly using deep learning.

Craniofacial anomaly including deformational plagiocephaly as a result of deformities in head and facial bones evolution is a serious health problem in newbies. The impact of such condition on the affected infants is profound from both medical and social viewpoint. Indeed, timely diagnosing through different medical examinations like anthropometric measurements of the skull or even Computer Tomography (CT) image modality followed by a periodical screening and monitoring plays a vital role in treatment phase. In this paper, a classification model for detecting and monitoring deformational plagiocephaly in affected infants is presented. The presented model is based on a deep learning network architecture. The given model achieves high accuracy of 99.01% with other classification parameters. The input to the model are the images captured by commonly used smartphone cameras which waives the requirement to sophisticated medical imaging modalities. The method is deployed into a mobile application which enables the parents/caregivers and non-clinical experts to monitor and report the treatment progress at home.

Running Behind "POPO"-Impact of Predictors of Poor Outcome for Treatment Stratification in Pediatric Crohn's Disease.

Background and Aims: Intensifying therapy for Paediatric Crohn's Disease (CD) by early use of immunomodulators and biologics has been proposed for cases in which predictors of poor outcome (POPO) were present. We investigated therapy stratifying potential comparing POPO-positive and -negative CD patients from CEDATA-GPGE®, a German-Austrian Registry for Paediatric Inflammatory Bowel disease. Methods: CD patients (1-18 years) registered in CEDATA-GPGE® (2004-2018) within 3 months of diagnosis and at least two follow-up visits were included. Disease course and treatments over time were analysed regarding positivity of POPO criteria and test statistical properties. Results: 709/1084 patients included had at least one POPO criterion (65.4%): 177 patients (16.3%) had persistent disease (POPO2), 581 (53.6%) extensive disease (POPO3), 21 (1.9%) severe growth retardation POPO4, 47 (4.3%) stricturing/penetrating disease (POPO6) and 122 (11.3%) perianal disease (POPO7). Patients with persistent disease differed significantly in lack of sustained remission >1 year (Odd Ratio (OR) 1.49 [1.07-2.07], p = 0.02), patients with initial growth failure in growth failure at end of observation (OR 51.16 [19.89-131.62], p < 0.0001), patients with stricturing and penetrating disease as well as perianal disease in need for surgery (OR 17.76 [9.39-33.58], p < 0.001; OR 2.56 [1.58-4.15], p < 0.001, respectively). Positive Predictive Value for lack of sustained remission was >60% for patients with initial growth failure, persistent or stricturing/penetrating disease. Conclusion: Predictors of poor outcome with complicated courses of disease were common in CEDATA-GPGE®. An early intensified approach for paediatric CD patients with POPO-positivity (POPO2-4, 6-7) should be considered, because they have an increased risk to fare poorly.

Machine Learning Classification of Inflammatory Bowel Disease in Children Based on a Large Real-World Pediatric Cohort CEDATA-GPGE® Registry.

Introduction: The rising incidence of pediatric inflammatory bowel diseases (PIBD) facilitates the need for new methods of improving diagnosis latency, quality of care and documentation. Machine learning models have shown to be applicable to classifying PIBD when using histological data or extensive serology. This study aims to evaluate the performance of algorithms based on promptly available data more suited to clinical applications. Methods: Data of inflammatory locations of the bowels from initial and follow-up visitations is extracted from the CEDATA-GPGE registry and two follow-up sets are split off containing only input from 2017 and 2018. Pre-processing excludes patients in remission and encodes the categorical data numerically. For classification of PIBD diagnosis, a support vector machine (SVM), a random forest algorithm (RF), extreme gradient boosting (XGBoost), a dense neural network (DNN) and a convolutional neural network (CNN) are employed. As best performer, a convolutional neural network is further improved using grid optimization. Results: The achieved accuracy of the optimized neural network reaches up to 90.57% on data inserted into the registry in 2018. Less performant methods reach 88.78% for the DNN down to 83.94% for the XGBoost. The accuracy of prediction for the 2018 follow-up dataset is higher than those for older datasets. Neural networks yield a higher standard deviation with 3.45 for the CNN compared to 0.83-0.86 of the support vector machine and ensemble methods. Discussion: The displayed accuracy of the convolutional neural network proofs the viability of machine learning classification in PIBD diagnostics using only timely available data.

Methods for Adventitious Respiratory Sound Analyzing Applications Based on Smartphones: A Survey.

Detection and classification of adventitious acoustic lung sounds plays an important role in diagnosing, monitoring, controlling and, caring the patients with lung diseases. Such systems can be presented as different platforms like medical devices, standalone software or smartphone application. Ubiquity of smartphones and widespread use of the corresponding applications make such a device an attractive platform for hosting the detection and classification systems for adventitious lung sounds. In this paper, the smartphone-based systems for automatic detection and classification of the adventitious lung sounds are surveyed. Such adventitious sounds include cough, wheeze, crackle and, snore. Relevant sounds related to abnormal respiratory activities are considered as well. The methods are shortly described and the analyzing algorithms are explained. The analysis includes detection and/or classification of the sound events. A summary of the main surveyed methods together with the classification parameters and used features for the sake of comparison is given. Existing challenges, open issues and future trends will be discussed as well.

Reprint of "The detection of knee joint sounds at defined loads by means of vibroarthrography".

BACKGROUND: Crepitus of the knee may mirror structural and functional changes in the joint during motion. Although the magnitude of these sounds increases with greater cartilage damage, it is unclear whether knee joint sounds also reflect joint loading. METHODS: Twelve healthy volunteers (mean 26 (SD 3.6) years, 7 females) participated in the randomized-balanced crossover study. Knee joint sounds were recorded (linear sampling, 5512 Hz) by means of two microphones, one placed on the medial tibial plateau and one on the patella. Two activities of daily living (standing up from/sitting down on a bench; descending stairs) and three open kinetic chain knee extension-flexion cycles (passive movement, 10% and 40% loading of the individual one repetition maximum) were performed. Each participant carried out three sets of five repetitions and three sets of 15 steps downwards (stairs), respectively. For data analysis, the mean sound amplitude and the median power frequency for each loading condition were determined. Friedman test and Bonferroni-Holm adjusted post-hoc test were performed to detect differences between conditions. FINDINGS: We obtained significant differences between joint sound amplitudes for all movements, both measured at the medial tibial plateau (Chi2 = 20.7, p < 0.001) and at the patella (Chi2 = 27.6, p < 0.001). We showed a significant difference in the median power frequency of the patella between all movements (Chi2 = 17.8, p < 0.5). INTERPRETATION: Overall, the larger the supposed knee joint loading was, the louder was the recorded knee crepitus. Consequently, vibroarthrographically assessed knee joint sounds can differ across knee joint loading conditions.

Disease control in patients with asthma and respiratory symptoms (wheezing, cough) during sleep.

INTRODUCTION: The Global Initiative for Asthma (GINA)-defined criteria for asthma control include questions about daytime symptoms, limitation of activity, nocturnal symptoms, need for reliever treatment and patients' satisfaction. Patients with nocturnal symptoms like wheezing and cough often suffer from lower sleep quality and impaired daytime performance. The lack of an appropriate method for standardized and objective monitoring of respiratory symptoms leads to difficulties in asthma management. The aim of this study is to present a new method for automated wheeze and cough detection during sleep and to assess the actual level of asthma control by the Asthma Control Test (ACT). METHODS: Respiratory symptoms like wheezing and cough were recorded with the LEOSound-Monitor for one night in 55 asthmatic patients in their individual domestic setting. Patients were asked to assess their level of asthma subjectively with the ACT. The study consisted of 37 women and 18 men, with a mean age of 41 years, and a mean BMI of 27 kg/m2. Most of the patients had been taking an ICS/LABA combination and would resort to a SABA as their rescue medication. RESULTS: 60% of the participants were classed as having controlled, and 40% were classed as having partially- or uncontrolled asthma. During sleep wheezing was found in 8 of the 55 asthma patients (14.5%) and coughing was found in 30 patients (54.5%). The median ACT score in wheezing-patients was 14, while in non-wheezing patients it was 21. Uncontrolled asthma was found in 6 of the 8 wheezing-patients. Coughing versus non-coughing patients did not show a significant difference in the ACT-score (20, 22 respectively). CONCLUSION: Wheezing is a sign of uncontrolled asthma. The ACT-score in wheezing patients is worse compared to patients without wheezing. LEOSound proofed to be a useful tool in providing an objective evaluation of respiratory symptoms, like coughing and wheezing. In clinical practice, this may allow an improvement in asthma therapy.

Comparison of Formative Evaluation Methods in the Usability Process on the Example of a Medical App.

BACKGROUND: The process of developing a medical device has become increasingly complex, not least because of the Medical Device Regulation. Some of the associated changes affect in particular the software development companies. One of the challenges to provide safe software products is the usability engineering process. Adequate methods must be identified to find severe usability issues effectively and efficiently. OBJECTIVES: The aim of this study was a comparison of normative recommended formative evaluation methods. METHODS: Two expert-based methods and two user-based methods were compared regarding effectiveness in finding issues, the level of detail and the temporal effort. RESULTS: The heuristics and the isometrics, both showed a significant advantage regarding the effectiveness and similarity in level of detail and temporal effort. CONCLUSION: Based on this paper, the heuristics and the isometrics, both can be recommended, but further studies are necessary to consolidate this statement. Also, further methods should be considered, and more test persons must be involved to give an overall comparison of formative evaluation methods in the usability process of medical apps.

Reliability of Vibroarthrography to Assess Knee Joint Sounds in Motion.

Knee acoustic emissions provide information about joint health and loading in motion. As the reproducibility of knee acoustic emissions by vibroarthrography is yet unknown, we evaluated the intrasession and interday reliability of knee joint sounds. In 19 volunteers (25.6 ± 2.0 years, 11 female), knee joint sounds were recorded by two acoustic sensors (16,000 Hz; medial tibial plateau, patella). All participants performed four sets standing up/sitting down (five repetitions each). For measuring intrasession reliability, we used a washout phase of 30 min between the first three sets, and for interday reliability we used a washout phase of one week between sets 3 and 4. The mean amplitude (dB) and median power frequency (Hz, MPF) were analyzed for each set. Intraclass correlation coefficients (ICCs (2,1)), standard errors of measurement (SEMs), and coefficients of variability (CVs) were calculated. The intrasession ICCs ranged from 0.85 to 0.95 (tibia) and from 0.73 to 0.87 (patella). The corresponding SEMs for the amplitude were ≤1.44 dB (tibia) and ≤2.38 dB (patella); for the MPF, SEMs were ≤13.78 Hz (tibia) and ≤14.47 Hz (patella). The intrasession CVs were ≤0.06 (tibia) and ≤0.07 (patella) (p < 0.05). The interday ICCs ranged from 0.24 to 0.33 (tibia) and from 0 to 0.82 (patella) for both the MPF and amplitude. The interday SEMs were ≤4.39 dB (tibia) and ≤6.85 dB (patella) for the amplitude and ≤35.39 Hz (tibia) and ≤15.64 Hz (patella) for the MPF. The CVs were ≤0.14 (tibia) and ≤0.08 (patella). Knee joint sounds were highly repeatable within a single session but yielded inconsistent results for the interday reliability.

The detection of knee joint sounds at defined loads by means of vibroarthrography.

BACKGROUND: Crepitus of the knee may mirror structural and functional changes in the joint during motion. Although the magnitude of these sounds increases with greater cartilage damage, it is unclear whether knee joint sounds also reflect joint loading. METHODS: Twelve healthy volunteers (mean 26 (SD 3.6) years, 7 females) participated in the randomized-balanced crossover study. Knee joint sounds were recorded (linear sampling, 5512 Hz) by means of two microphones, one placed on the medial tibial plateau and one on the patella. Two activities of daily living (standing up from/sitting down on a bench; descending stairs) and three open kinetic chain knee extension-flexion cycles (passive movement, 10% and 40% loading of the individual one repetition maximum) were performed. Each participant carried out three sets of five repetitions and three sets of 15 steps downwards (stairs), respectively. For data analysis, the mean sound amplitude and the median power frequency for each loading condition were determined. Friedman test and Bonferroni-Holm adjusted post-hoc test were performed to detect differences between conditions. FINDINGS: We obtained significant differences between joint sound amplitudes for all movements, both measured at the medial tibial plateau (Chi2 = 20.7, p < 0.001) and at the patella (Chi2 = 27.6, p < 0.001). We showed a significant difference in the median power frequency of the patella between all movements (Chi2 = 17.8, p < 0.5). INTERPRETATION: Overall, the larger the supposed knee joint loading was, the louder was the recorded knee crepitus. Consequently, vibroarthrographically assessed knee joint sounds can differ across knee joint loading conditions.