Attributes, Methods, and Frameworks Used to Evaluate Wearables and Their Companion mHealth Apps: Scoping Review.

BACKGROUND: Wearable devices, mobile technologies, and their combination have been accepted into clinical use to better assess the physical fitness and quality of life of patients and as preventive measures. Usability is pivotal for overcoming constraints and gaining users' acceptance of technology such as wearables and their companion mobile health (mHealth) apps. However, owing to limitations in design and evaluation, interactive wearables and mHealth apps have often been restricted from their full potential. OBJECTIVE: This study aims to identify studies that have incorporated wearable devices and determine their frequency of use in conjunction with mHealth apps or their combination. Specifically, this study aims to understand the attributes and evaluation techniques used to evaluate usability in the health care domain for these technologies and their combinations. METHODS: We conducted an extensive search across 4 electronic databases, spanning the last 30 years up to December 2021. Studies including the keywords "wearable devices," "mobile apps," "mHealth apps," "physiological data," "usability," "user experience," and "user evaluation" were considered for inclusion. A team of 5 reviewers screened the collected publications and charted the features based on the research questions. Subsequently, we categorized these characteristics following existing usability and wearable taxonomies. We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. RESULTS: A total of 382 reports were identified from the search strategy, and 68 articles were included. Most of the studies (57/68, 84%) involved the simultaneous use of wearables and connected mobile apps. Wrist-worn commercial consumer devices such as wristbands were the most prevalent, accounting for 66% (45/68) of the wearables identified in our review. Approximately half of the data from the medical domain (32/68, 47%) focused on studies involving participants with chronic illnesses or disorders. Overall, 29 usability attributes were identified, and 5 attributes were frequently used for evaluation: satisfaction (34/68, 50%), ease of use (27/68, 40%), user experience (16/68, 24%), perceived usefulness (18/68, 26%), and effectiveness (15/68, 22%). Only 10% (7/68) of the studies used a user- or human-centered design paradigm for usability evaluation. CONCLUSIONS: Our scoping review identified the types and categories of wearable devices and mHealth apps, their frequency of use in studies, and their implementation in the medical context. In addition, we examined the usability evaluation of these technologies: methods, attributes, and frameworks. Within the array of available wearables and mHealth apps, health care providers encounter the challenge of selecting devices and companion apps that are effective, user-friendly, and compatible with user interactions. The current gap in usability and user experience in health care research limits our understanding of the strengths and limitations of wearable technologies and their companion apps. Additional research is necessary to overcome these limitations.

Usability and User Experience of an mHealth App for Therapy Support of Patients With Breast Cancer: Mixed Methods Study Using Eye Tracking.

BACKGROUND: Early identification of quality of life (QoL) loss and side effects is a key challenge in breast cancer therapy. Digital tools can be helpful components of therapeutic support. Enable, a smartphone app, was used in a multicenter, prospective randomized controlled trial in 3 breast cancer centers. The app simultaneously serves as a therapy companion (eg, by displaying appointments), a tool for documenting QoL (eg, by enabling data collection for QoL questionnaires), and documentation of patient-reported side effects. The need for digital tools is continually rising. However, evidence of the effects of long-term use of mobile health (mHealth) apps in aftercare for patients with breast cancer is limited. Therefore, evaluating the usability and understanding the user experience of this mHealth app could potentially contribute valuable insights in this field. OBJECTIVE: A usability study was conducted to explore how patients with breast cancer receiving neoadjuvant, adjuvant, or palliative outpatient treatment rated their engagement with the app , the user experience, and the benefits of using the app. METHODS: A mixed methods approach was chosen to combine subjective and objective measures, including an eye-tracking procedure, a standardized usability questionnaire (mHealth App Usability Questionnaire), and semistructured interviews. Participants were surveyed twice during the study period. Interviews were transcribed verbatim and analyzed using thematic analysis. Analysis of the eye-tracking data was carried out using the tracker-integrated software. Descriptive analysis was conducted for the quantitative data. RESULTS: The mHealth App Usability Questionnaire results (n=105) indicated good overall usability for 2 different time points (4 wk: mean 89.15, SD 9.65; 20 wk: mean 85.57, SD 12.88). The qualitative analysis of the eye-tracking recordings (n=10) and interviews (n=16) showed that users found the Enable app easy to use. The design of the app, information about therapies and side effects, and usefulness of the app as a therapy companion were rated positively. Additionally, participants contributed requests for additional app features and suggestions for improving the content and usability of the app. Relevant themes included optimization of the appointment feature, updating the app's content regularly, and self-administration. In contrast to the app's current passive method of operation, participants expressed a desire for more active engagement through messaging, alarms, or emails. CONCLUSIONS: The results of this study demonstrate the good usability of the Enable app as well as the potential for further development. We concluded from patients' feedback and requests that mHealth apps could benefit from giving patients a more active role (eg, being able to actively document side effects as they occur). Additionally, regular updates of app content could further contribute to encouraging continued use of mHealth apps. Our findings may also assist other researchers in tailoring their mHealth apps to the actual needs of patients undergoing breast cancer therapy.

Isolation and Quantification of Bacterial Membrane Vesicles for Quantitative Metabolic Studies Using Mammalian Cell Cultures.

Bacterial membrane vesicles (BMVs) are produced by most bacteria and participate in various cellular processes, such as intercellular communication, nutrient exchange, and pathogenesis. Notably, these vesicles can contain virulence factors, including toxic proteins, DNA, and RNA. Such factors can contribute to the harmful effects of bacterial pathogens on host cells and tissues. Although the general effects of BMVs on host cellular physiology are well known, the underlying molecular mechanisms are less understood. In this study, we introduce a vesicle quantification method, leveraging the membrane dye FM4-64. We utilize a linear regression model to analyze the fluorescence emitted by stained vesicle membranes to ensure consistent and reproducible vesicle-host interaction studies using cultured cells. This method is particularly valuable for identifying host cellular processes impacted by vesicles and their specific cargo. Moreover, it outcompetes unreliable protein concentration-based methods. We (1) show a linear correlation between the number of vesicles and the fluorescence signal emitted from the FM4-64 dye; (2) introduce the "vesicle load" as a new semi-quantitative unit, facilitating more reproducible vesicle-cell culture interaction experiments; (3) show that a stable vesicle load yields consistent host responses when studying vesicles from Pseudomonas aeruginosa mutants; (4) demonstrate that typical vesicle isolation contaminants, such as flagella, do not significantly skew the metabolic response of lung epithelial cells to P. aeruginosa vesicles; and (5) identify inositol monophosphatase 1 (SuhB) as a pivotal regulator in the vesicle-mediated pathogenesis of P. aeruginosa.

TGF-ß Activated Kinase 1 (TAK1) Is Activated in Microglia After Experimental Epilepsy and Contributes to Epileptogenesis.

Increasing evidence suggests that inflammation promotes epileptogenesis. TAK1 is a central enzyme in the upstream pathway of NF-κB and is known to play a central role in promoting neuroinflammation in neurodegenerative diseases. Here, we investigated the cellular role of TAK1 in experimental epilepsy. C57Bl6 and transgenic mice with inducible and microglia-specific deletion of Tak1 (Cx3cr1CreER:Tak1fl/fl) were subjected to the unilateral intracortical kainate mouse model of temporal lobe epilepsy (TLE). Immunohistochemical staining was performed to quantify different cell populations. The epileptic activity was monitored by continuous telemetric electroencephalogram (EEG) recordings over a period of 4 weeks. The results show that TAK1 was activated predominantly in microglia at an early stage of kainate-induced epileptogenesis. Tak1 deletion in microglia resulted in reduced hippocampal reactive microgliosis and a significant decrease in chronic epileptic activity. Overall, our data suggest that TAK1-dependent microglial activation contributes to the pathogenesis of chronic epilepsy.

Associations between the implementation of telework strategies and job performance: Moderating influences of boundary management preferences and telework experience.

Boosted by the COVID-19 pandemic, more than ever, an organization's success depends on its teleworkers' performance. However, little attention has been paid to the individual strategies implemented by teleworkers to achieve goals such as drawing boundaries between work- and private-life, working task-oriented and productively, and keeping social contact. We collected quantitative survey data of 548 teleworkers indicating their implementation of 85 telework strategies derived from scientific literature and popular media (e.g., working in a separate room, wearing work clothes at home), self-reported job performance, boundary management preferences, and telework experience. We identified (a) the implementation of telework strategies, (b) associations with job performance, (c) divergences between the implementation and the performance association, and (d) moderating influences of boundary management preferences and telework experience. The results suggest that the most implemented telework strategies tend to be the ones most positively associated with job performance. These telework strategies serve goals related to working task-oriented and productively by adopting a conducive work attitude as well as keeping social contact by using modern communication technology rather than goals related to drawing boundaries between work- and private-life. The findings underscore the benefits of expanding a narrow focus on telework strategies stemming from boundary theory to unravel telework strategies' puzzling impacts on (tele-) work outcomes. Also, taking a person-environment fit perspective appeared to be a promising approach to tailor evidence-based best practice telework strategies to teleworkers' individual preferences and needs (boundary management preferences and telework experience).

Effects of talking about side effects versus not talking about side effects on the therapeutic alliance: A controlled clinical trial.

INTRODUCTION: Side effects of psychotherapy are common. Therapists and patients must recognize negative developments to take countermeasure. Therapists can be reluctant to talk about problems of their own treatment. The hypothesis could be that talking about side effects can impair the therapeutic relationship. METHODS: We examined whether a systematic monitoring and discussion of side effects has a negative effect on therapeutic alliance. Intervention group (IG) therapists and patients filled in the UE-PT scale (unwanted events in the view of patient and therapists scale) and discussed their mutual ratings (IG, n = 20). As unwanted events can be independent of therapy, but also be treatment-related side effects, the UE-PT-scale first asks for UE and then for their relation to the ongoing treatment. In the control group (CG, n = 16) treatment was done without any special side effect monitoring. Both groups filled in the Scale for Therapeutic Alliance (STA-R). RESULTS: IG-therapists reported various unwanted events in 100% and patients in 85% of cases: complexity of problems, burdensome or overdemanding therapy, problems with work, and symptom deterioration. Any side effect was reported in 90% by therapists and in 65% by patients. Most frequent side effects were demoralization and worsening of symptoms. IG therapists observed an improvement of global therapeutic alliance in STA-R (M = 3.08 to M = 3.31, p = 0.024, interaction effect in ANOVA with two groups and measurement repetition), and reduced patient fear (M = 1.21 to M = 0.91, p = 0.012). IG patients perceived improvement in bond (M = 3.45 to M = 3.70, p = 0.045). In the CG no comparable changes were seen (alliance M = 2.97 to M = 3.00; patient fear M = 1.20 to M = 1.36; patient-perceived bond M = 3.41 to M = 3.36). CONCLUSION: The initial hypothesis must be rejected. The results suggest that monitoring, and discussion of side effects can even improve the therapeutic alliance. Therapists must not be afraid that this will endanger the therapeutic process. The use of a standardized instrument like the UE-PT-scale seems helpful.

Reactive microglia are the major source of tumor necrosis factor alpha and contribute to astrocyte dysfunction and acute seizures in experimental temporal lobe epilepsy.

Extensive microglia reactivity has been well described in human and experimental temporal lobe epilepsy (TLE). To date, however, it is not clear whether and based on which molecular mechanisms microglia contribute to the development and progression of focal epilepsy. Astroglial gap junction coupled networks play an important role in regulating neuronal activity and loss of interastrocytic coupling causally contributes to TLE. Here, we show in the unilateral intracortical kainate (KA) mouse model of TLE that reactive microglia are primary producers of tumor necrosis factor (TNF)α and contribute to astrocyte dysfunction and severity of status epilepticus (SE). Immunohistochemical analyses revealed pronounced and persistent microglia reactivity, which already started 4 h after KA-induced SE. Partial depletion of microglia using a colony stimulating factor 1 receptor inhibitor prevented early astrocyte uncoupling and attenuated the severity of SE, but increased the mortality of epileptic mice following surgery. Using microglia-specific inducible TNFα knockout mice we identified microglia as the major source of TNFα during early epileptogenesis. Importantly, microglia-specific TNFα knockout prevented SE-induced gap junction uncoupling in astrocytes. Continuous telemetric EEG recordings revealed that during the first 4 weeks after SE induction, microglial TNFα did not significantly contribute to spontaneous generalized seizure activity. Moreover, the absence of microglial TNFα did not affect the development of hippocampal sclerosis but attenuated gliosis. Taken together, these data implicate reactive microglia in astrocyte dysfunction and network hyperexcitability after an epileptogenic insult.

Nociceptive two-point discrimination acuity and body representation failure in polyneuropathy.

OBJECTIVES: Although patients' complaints suggest polyneuropathy (PNP) and neuropathic pain, routine investigations do not always support the diagnosis. Assessing two-point-pain discrimination thresholds (2ptDT) and quantify body representation disturbances might be useful to close this diagnostic gap. METHODS: Pinprick pain and laser-heat pain perception thresholds and 2ptDT on hands, forearms, lower legs and feet were obtained in 20 PNP patients (mean age: 57.6 ± 13.9) and 20 healthy subjects (mean age: 50.6 ± 4.7 years). Body representation disturbances were assessed by self-estimating feet size and the Bath CRPS body perception disturbances questionnaire adapted for PNP. RESULTS: Pain perception thresholds and laser-heat pain 2ptDT were unaltered, but patients had higher pinprick pain 2ptDT then the healthy subjects. The 2ptDT for pinprick at the hands discriminate best between groups (U-test; p=0.001). Furthermore, patients estimated their feet longer than they are. In subsequent multivariate discriminant analyses, 2ptDT for pinprick pain at the hands, 2ptDT for laser-heat pain and the perception thresholds for laser-heat pain at the feet classified 85% of PNP vs. HC correctly. The combination of 2ptDT for pinprick pain at the hands, pinprick pain perception thresholds at the calves and foot length estimation differentiates painful vs. non-painful PNPs correctly in 90% of the cases. CONCLUSIONS: Testing 2ptDT for painful pinprick stimuli at the hands and asking for foot length estimation might add to diagnostic accuracy in painful PNP.

Effect of shape and size of supraspinatus tears on rotator cuff strain distribution: an in vitro study.

BACKGROUND: The impact of the size and shape of a supraspinatus tear on the strain of the intact rotator cuff and the kinematics of the shoulder is still unknown. This, however, can be relevant when deciding whether surgical reconstruction is required to prevent an increase in a tendon defect. In this study, the effect of tear width and shape on rotator cuff strain and glenohumeral kinematics was evaluated during active abduction. METHODS: Twelve fresh-frozen cadaveric shoulders with intact rotator cuffs were used in this study. We created 50% and 100% wide (full-thickness) crescent-shaped (CS) tears (n = 6) and reverse L-shaped (rLS) tears (n = 6) in the supraspinatus tendon and measured strain and kinematics during active humeral elevation until 30°. RESULTS: Both tear shapes and sizes led to an increase in internal rotation, supraspinatus loading force, and superior translation of the humerus. For the 100% wide tear size, anterior translation was observed in the CS tear group, whereas in the rLS tear group, this translation occurred mainly in the posterior direction. Strain was higher in the infraspinatus during the first 25° of abduction in comparison with the supraspinatus tendon in both tear shape groups. An analysis of the anterior and posterior tear borders showed a higher strain concentration on the same side of the tear in the CS tear group with 50% and 100% wide tears. CONCLUSIONS: The influence of different tear shapes on translation in the anterior-posterior direction was evident as both CS and rLS tears led to an oppositely directed translation of the humeral head. The strain analysis showed a stress-shielding effect of the infraspinatus at the beginning of abduction. Therefore, special attention must be paid to correctly identify the tear extension and adequately reconstruct the rotator cuff footprint. Moreover, the constant location of maximum strain in the CS tear group may lead to an earlier progression than in the rLS tear group.

Eigenvalue productivity: Measurement of individual contributions in teams.

While the output of a team is evident, the productivity of each team member is typically not readily identifiable. In this paper we consider the problem of measuring the productivity of team members. We propose a new concept of coworker productivity, which we refer to as eigenvalue productivity (EVP). We demonstrate the existence and uniqueness of our concept and show that it possesses several desirable properties. Also, we suggest a procedure for specifying the required productivity matrix of a team, and illustrate the operational practicability of EVP by means of three examples representing different types of available data.

Mobile Access to Medical Records in Heart Transplantation Aftercare: Mixed-Methods Study Assessing Usability, Feasibility and Effects of a Mobile Application.

BACKGROUND: Patient access to medical records can improve quality of care. The phellow application (app) was developed to provide patients access to selected content of their medical record. It was tested at a heart transplantation (HTx) outpatient clinic. The aims of this study were (1) to assess usability of phellow, (2) to determine feasibility of implementation in routine care, and (3) to study the effects app use had on patients' self-management. METHODS: Usability was measured quantitatively through the System Usability Scale (SUS). Furthermore, usability, feasibility, and effects on self-management were qualitatively assessed through interviews with users, non-users, and health care providers. RESULTS: The SUS rating (n = 31) was 79.9, indicating good usability. Twenty-three interviews were conducted. Although appreciation and willingness-to-use were high, usability problems such as incompleteness of record, technical issues, and complex registration procedures were reported. Improved technical support infrastructure, clearly defined responsibilities, and app-specific trainings were suggested for further implementation. Patients described positive effects on their self-management. CONCLUSIONS: To be feasible for implementation in routine care, usability problems should be addressed. Feedback on the effect of app use was encouraging. Accompanying research is crucial to monitor usability improvements and to further assess effects of app use on patients.

Perspective of Information Technology Decision Makers on Factors Influencing Adoption and Implementation of Artificial Intelligence Technologies in 40 German Hospitals: Descriptive Analysis.

BACKGROUND: New artificial intelligence (AI) tools are being developed at a high speed. However, strategies and practical experiences surrounding the adoption and implementation of AI in health care are lacking. This is likely because of the high implementation complexity of AI, legacy IT infrastructure, and unclear business cases, thus complicating AI adoption. Research has recently started to identify the factors influencing AI readiness of organizations. OBJECTIVE: This study aimed to investigate the factors influencing AI readiness as well as possible barriers to AI adoption and implementation in German hospitals. We also assessed the status quo regarding the dissemination of AI tools in hospitals. We focused on IT decision makers, a seldom studied but highly relevant group. METHODS: We created a web-based survey based on recent AI readiness and implementation literature. Participants were identified through a publicly accessible database and contacted via email or invitational leaflets sent by mail, in some cases accompanied by a telephonic prenotification. The survey responses were analyzed using descriptive statistics. RESULTS: We contacted 609 possible participants, and our database recorded 40 completed surveys. Most participants agreed or rather agreed with the statement that AI would be relevant in the future, both in Germany (37/40, 93%) and in their own hospital (36/40, 90%). Participants were asked whether their hospitals used or planned to use AI technologies. Of the 40 participants, 26 (65%) answered "yes." Most AI technologies were used or planned for patient care, followed by biomedical research, administration, and logistics and central purchasing. The most important barriers to AI were lack of resources (staff, knowledge, and financial). Relevant possible opportunities for using AI were increase in efficiency owing to time-saving effects, competitive advantages, and increase in quality of care. Most AI tools in use or in planning have been developed with external partners. CONCLUSIONS: Few tools have been implemented in routine care, and many hospitals do not use or plan to use AI in the future. This can likely be explained by missing or unclear business cases or the need for a modern IT infrastructure to integrate AI tools in a usable manner. These shortcomings complicate decision-making and resource attribution. As most AI technologies already in use were developed in cooperation with external partners, these relationships should be fostered. IT decision makers should assess their hospitals' readiness for AI individually with a focus on resources. Further research should continue to monitor the dissemination of AI tools and readiness factors to determine whether improvements can be made over time. This monitoring is especially important with regard to government-supported investments in AI technologies that could alleviate financial burdens. Qualitative studies with hospital IT decision makers should be conducted to further explore the reasons for slow AI.

Bacterial Growth, Communication, and Guided Chemotaxis in 3D-Bioprinted Hydrogel Environments.

Bioprinting of engineered bacteria is of great interest for applications of synthetic biology in the context of living biomaterials, but so far, only a few viable approaches are available for the printing of gels hosting live Escherichia coli bacteria. Here, we develop a gentle extrusion-based bioprinting method based on an inexpensive alginate/agarose ink mixture that enables printing of E. coli into three-dimensional hydrogel structures up to 10 mm in height. We first characterize the rheological properties of the gel ink and then study the growth of the bacteria inside printed structures. We show that the maturation of fluorescent proteins deep within the printed structures can be facilitated by the addition of a calcium peroxide-based oxygen generation system. We then utilize the bioprinter to control different types of interactions between bacteria that depend on their spatial position. We next show quorum-sensing-based chemical communication between the engineered sender and receiver bacteria placed at different positions inside the bioprinted structure and finally demonstrate the fabrication of barrier structures defined by nonmotile bacteria that can guide the movement of chemotactic bacteria inside a gel. We anticipate that a combination of 3D bioprinting and synthetic biological approaches will lead to the development of living biomaterials containing engineered bacteria as dynamic functional units.

Experimental study of an implantable fiber-optic microphone on human cadavers.

In this paper, we present the results of an experimental study about a novel fiber optical vibrometer, aimed to be used as a totally implantable fiber-optic microphone for hearing aids. The sensor head, implanted inside the human cadaver middle ear, detects the amplitude of the incus vibrations, which are produced by an external acoustical source. The probe beam of coherent vertical cavity surface emitting laser (VCSEL) radiation is directed to the incus and the phase-modulated reflected beam is captured and demodulated. The problem of interferometric fading was solved using two quasi-quadrature signals, passively produced by the 3 × 3 single-mode fiber-optic coupler, processed by a special embedded algorithm. The implanted optoelectronic module works with very low-power consumption, performs real-time signal processing and outputs an analogue signal proportional to the incus vibration. The amplitude of the incus vibrations at different sound pressure levels (SPL) from 40 to 90 dB and at frequencies from 100 Hz to 10 kHz were measured by the implanted system. The system was evaluated on five cadaver skulls. The measured amplitudes were in the range of 1 pm to 5 nm, depending on the subjected skull and the applied sound pressure.

Perhexiline treatment improves toxic effects of ß-adrenergic receptor stimulation in experimental peripartum cardiomyopathy.

AIMS: Peripartum cardiomyopathy (PPCM) is a pregnancy-associated cardiomyopathy that occurs in previously heart-healthy women towards the end of pregnancy or in the first months after delivery and is characterized by heart failure due to systolic dysfunction. The clinical course of PPCM differs between mild symptoms and severe forms with acute heart failure complicated by cardiogenic shock (CS). Treatment of CS complicating PPCM is challenging, as ß-adrenergic receptor (ß-AR) stimulation seems to be associated with progression of heart failure and adverse outcome. This experimental study aims to examine whether postpartum treatment with the glucose uptake-promoting drug perhexiline alone or as co-treatment with ß-AR stimulation prevents heart failure in the experimental PPCM mouse model. METHODS AND RESULTS: Postpartum (PP) female PPCM-prone mice with a cardiomyocyte-restricted STAT3-deficiency (αMHC-Cretg/+ ;Stat3fl/fl ; CKO) were treated with perhexiline over two to three pregnancies and nursing periods (2/3PP) or were co-treated with perhexiline after one pregnancy (1PP) under chronic ß-AR stimulation using isoproterenol (Iso) infusion. Perhexiline was not able to prevent onset of PPCM in CKO mice (FS: CKO Pexsig-2/3PP: 25 ± 12% vs. CKO Ctrl-2/3PP: 24 ± 9%, n.s.) but attenuated worsening of left ventricular function in response to treatment with the ß-AR agonist Iso (FS: CKO Pexsig-Iso-1PP: 19 ± 4% vs. CKO Ctrl-Iso-1PP: 11 ± 5%, P < 0.05). CONCLUSIONS: Treatment of PPCM patients with ß-AR agonists should be avoided whenever possible. In cases with CS complicating PPCM, when treatment with ß-AR agonists cannot be prevented, co-medication with perhexiline might help to reduce the cardiotoxic side effects of ß-AR stimulation. Clinical data are necessary to further validate this therapeutic approach.

Circulation of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli of Pandemic Sequence Types 131, 648, and 410 Among Hospitalized Patients, Caregivers, and the Community in Rwanda.

Multi-drug resistant (MDR), gram-negative Enterobacteriaceae, such as Escherichia coli (E. coli) limit therapeutic options and increase morbidity, mortality, and treatment costs worldwide. They pose a serious burden on healthcare systems, especially in developing countries like Rwanda. Several studies have shown the effects caused by the global spread of extended-spectrum beta-lactamase (ESBL)-producing E. coli. However, limited data is available on transmission dynamics of these pathogens and the mobile elements they carry in the context of clinical and community locations in Sub-Saharan Africa. Here, we examined 120 ESBL-producing E. coli strains from patients hospitalized in the University Teaching Hospital of Butare (Rwanda), their attending caregivers as well as associated community members and livestock. Based on whole-genome analysis, the genetic diversification and phylogenetics were assessed. Moreover, the content of carried plasmids was characterized and investigated for putative transmission among strains, and for their potential role as drivers for the spread of antibiotic resistance. We show that among the 30 different sequence types (ST) detected were the pandemic clonal lineages ST131, ST648 and ST410, which combine high-level antimicrobial resistance with virulence. In addition to the frequently found resistance genes bla CTX-M-15 , tet(34), and aph(6)-Id, we identified csg genes, which are required for curli fiber synthesis and thus biofilm formation. Numerous strains harbored multiple virulence-associated genes (VAGs) including pap (P fimbriae adhesion cluster), fim (type I fimbriae) and chu (Chu heme uptake system). Furthermore, we found phylogenetic relationships among strains from patients and their caregivers or related community members and animals, which indicates transmission of pathogens. Also, we demonstrated the presence and potential transfer of identical/similar ESBL-plasmids in different strains from the Rwandan setting and when compared to an external plasmid. This study highlights the circulation of clinically relevant, pathogenic ESBL-producing E. coli among patients, caregivers and the community in Rwanda. Combining antimicrobial resistance with virulence in addition to the putative exchange of mobile genetic elements among bacterial pathogens poses a significant risk around the world.

Intensified lipid-lowering treatment with alirocumab in patients with coronary heart disease.

BACKGROUND: Atherosclerotic cardiovascular disease is the leading cause of death and disability in the Western world. OBJECTIVE: To characterise adults with confirmed coronary heart disease (CHD) and primary heterozygous familial or non-familial hypercholesterolaemia or mixed dyslipidaemia who received alirocumab in a real-world setting. METHODS: This open, prospective, multicentre, non-interventional study, conducted in Germany, enroled patients with confirmed CHD who were treated with alirocumab according to its summary of product characteristics. Prescription was at the physician's discretion and independent of study participation. Patients were followed for 12 weeks after alirocumab initiation. RESULTS: In total, 245 patients (mean age 62.2 years; 34.0% female) were documented at 90 sites. Overall, 47.7% had familial hypercholesterolaemia, 48.9% non-familial hypercholesterolaemia and 43.8% mixed dyslipidaemia; 74.6% had hypertension and 29.2% diabetes mellitus. The most common lipid-lowering therapy in the 12 months preceding alirocumab was a statin, often in combination with ezetimibe (73.5%). Statin contraindications were documented for 46.2% patients and statin intolerance for 63.8%. The mean low-density lipoprotein cholesterol (LDL-C)-level prior to alirocumab was 150.5±51.6 mg/dL. Alirocumab prescription was in compliance with German national recommendations and/or European guidelines. The most common starting dose was 75 mg every other week. Overall, 57% patients reached target LDL-C levels (<70 mg/dL) after 12 weeks of treatment. Alirocumab was generally well tolerated. CONCLUSION: In a real-world setting in Germany, alirocumab was prescribed for patients with atherosclerotic cardiovascular disease who had high baseline LDL-C levels with or without statin intolerance. Efficacy and safety were consistent with findings observed in the ODYSSEY Phase III programme.

DNA methylation profiles of bronchoscopic biopsies for the diagnosis of lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in most western countries in both, males and females, accounting for roughly 20-25% of all cancer deaths. For choosing the most appropriate therapy regimen a definite diagnosis is a prerequisite. However, histological characterization of bronchoscopic biopsies particularly with low tumor cell content is often challenging. Therefore, this study aims at (a) determining the value of DNA methylation analysis applied to specimens obtained by bronchoscopic biopsy for the diagnosis of lung cancer and (b) at comparing aberrantly CpG loci identified in bronchoscopic biopsy with those identified by analyzing surgical specimens. RESULTS: We report the HumanMethylation450-based DNA methylation analysis of paired samples of bronchoscopic biopsy specimens either from the tumor side or from the contralateral tumor-free bronchus in 37 patients with definite lung cancer diagnosis and 18 patients with suspicious diagnosis. A differential DNA methylation analysis between both biopsy sites of patients with definite diagnosis identified 1303 loci. Even those samples were separated by the set of 1303 loci in which histopathological analysis could not unambiguously define the dignity. Further differential DNA methylation analyses distinguished between SCLC and NSCLC. We validated our results in an independent cohort of 40 primary lung cancers obtained by open surgical resection and their corresponding controls from the same patient as well as in publically available DNA methylation data from a TCGA cohort which could also be classified with high accuracy. CONCLUSIONS: Considering that the prognosis correlates with tumor stage at time of diagnosis, early detection of lung cancer is vital and DNA methylation analysis might add valuable information to reliably characterize lung cancer even in histologically ambiguous sample material.

Beyond Known Barriers-Assessing Physician Perspectives and Attitudes Toward Introducing Open Health Records in Germany: Qualitative Study.

BACKGROUND: Giving patients access to their medical records (ie, open health records) can support doctor-patient communication and patient-centered care and can improve quality of care, patients' health literacy, self-care, and treatment adherence. In Germany, patients are entitled by law to have access to their medical records. However, in practice doing so remains an exception in Germany. So far, research has been focused on organizational implementation barriers. Little is known about physicians' attitudes and perspectives toward opening records in German primary care. OBJECTIVE: This qualitative study aims to provide a better understanding of physicians' attitudes toward opening records in primary care in Germany. To expand the knowledge base that future implementation programs could draw from, this study focuses on professional self-conception as an influencing factor regarding the approval for open health records. Perspectives of practicing primary care physicians and advanced medical students were explored. METHODS: Data were collected through semistructured guide-based interviews with general practitioners (GPs) and advanced medical students. Participants were asked to share their perspectives on open health records in German general practices, as well as perceived implications, their expectations for future medical records, and the conditions for a potential implementation. Data were pseudonymized, audiotaped, and transcribed verbatim. Themes and subthemes were identified through thematic analysis. RESULTS: Barriers and potential advantages were reported by 7 GPs and 7 medical students (N=14). The following barriers were identified: (1) data security, (2) increased workload, (3) costs, (4) the patients' limited capabilities, and (5) the physicians' concerns. The following advantages were reported: (1) patient education and empowerment, (2) positive impact on the practice, and (3) improved quality of care. GPs' professional self-conception influenced their approval for open records: GPs considered their aspiration for professional autonomy and freedom from external control to be threatened and their knowledge-based support of patients to be obstructed by open records. Medical students emphasized the chance to achieve shared decision making through open records and expected the implementation to be realistic in the near future. GPs were more hesitant and voiced a strong resistance toward sharing notes on perceptions that go beyond clinical data. Reliable technical conditions, the participants' consent, and a joint development of the implementation project to meet the GPs' interests were requested. CONCLUSIONS: Open health record concepts can be seen as a chance to increase transparency in health care. For a potential future implementation in Germany, thorough consideration regarding the compatibility of GPs' professional values would be warranted. However, the medical students' positive attitude provides an optimistic perspective. Further research and a broad support from decision makers would be crucial to establish open records in Germany.