Viral Load Dynamics in SARS-CoV-2 Omicron Breakthrough Infections.

To determine viral dynamics in Omicron breakthrough infections, we measured severe acute respiratory syndrome coronavirus 2 RNA in 206 double-vaccinated or boostered individuals. During the first 3 days following the onset of symptoms, viral loads were significantly higher (cycle threshold [Ct], 21.76) in vaccinated compared to boostered (Ct, 23.14) individuals (P = .029). However, by performing a longitudinal analysis on 32 individuals over 14 days, no difference in the viral load trajectory was observed between double-vaccinated and boostered patients. Our results indicate that booster immunization results in a reduction in detectable viral loads without significantly changing viral load dynamics over time.

Digital Competencies and Attitudes Toward Digital Adherence Solutions Among Elderly Patients Treated With Novel Anticoagulants: Qualitative Study.

BACKGROUND: Nonadherence to medication is a driver of morbidity and mortality, and complex medication regimens in patients with chronic diseases foster the problem. Digital technology might help, but despite numerous solutions being developed, none are currently widely used, and acceptance rates remain low, especially among the elderly. OBJECTIVE: This study aimed to better understand and operationalize how new digital solutions can be evaluated. Particularly, the goal was to identify factors that help digital approaches targeting adherence to become more widely accepted. METHODS: A qualitative study using a conceptual grounded theory approach was conducted. We included patients aged 65 years and older who routinely took new oral anticoagulants. To generate theses about the digital competencies of the target group with daily medication intake, face-to-face interviews were conducted, recorded, and anonymized. After coding the interviews, categories were generated, discussed, and combined with several theses until saturation of the statements was reached. RESULTS: The methodological approach led to the finding that after interviews in 20 of 77 potentially available patients, a saturation of statements was reached. The average patient's age was 75 years, and 50% (10/20) of the subjects were female. The data identified five main coding categories-Diseases and medicine, Technology, Autonomy, Patient narrative, and Attitude toward technologies-each including positive and negative subcategories. Main categories and subcategories were summarized as Adherence Radar, which can be considered as a framework to assess the potential of adherence solutions in the process of prototyping and can be applied to all adherence tools in a holistic manner. CONCLUSIONS: The Adherence Radar can be used to increase the acceptance rate of digital solutions targeting adherence. For a patient-centric design, an app should be adapted to the individual patient's needs. According to our results, this application should be based on gender and educational background as well as the individual physician-patient relationship. If used in a proper, individualized manner, digital adherence solutions could become a new cornerstone for the treatment of chronically ill individuals.

Perception of the Progressing Digitization and Transformation of the German Health Care System Among Experts and the Public: Mixed Methods Study.

BACKGROUND: Health care systems worldwide are struggling to keep rising costs at bay with only modest outcome improvement among many diseases. Digitization with technologies like Artificial Intelligence or Machine Learning algorithms might address this. Although digital technologies have been successfully applied in clinical studies the effect on the overall health care system so far was limited. The regulatory ecosystem or data privacy might be responsible, but other reasons may also predominate. OBJECTIVE: We analyzed how the digitization of the German health care market is currently perceived among different stakeholders and investigated reasons for its slow adaption. METHODS: This was a mixed methods study split into a qualitative Part A using the conceptual approach of the Grounded Theory and a quantitative Part B using the Delphi method. For Part A we interviewed experts in the health care system and converted the results into 17 hypotheses. The Delphi method consisted of an online survey which was sent to the participants via email and was available for three months. For the assessment of the 17 hypotheses, the participants were given a six-point Likert scale. The participants were grouped into patients, physicians, and providers of services within the German health care market. RESULTS: There was a strong alignment of opinions on the hypotheses between experts (N=21) and survey participants (N=733), with 70.5% overall agreement on 12/17 hypotheses. Physicians demonstrated the lowest level of agreement with the expert panel at 88% (15/17) disagreement, with the hypotheses "H8: Digitization in the health care system will free up jobs," and "H6: Digitization in the health care system will empower the patients," perceived to be in profound disagreement (P=.036 and P<.001, respectively). CONCLUSIONS: Despite the firm agreement among participants and experts regarding the impact of digitization on the health care system, physicians demonstrated a more negative attitude. We assume that this might be a factor contributing to the slow adoption of digitization in practice. Physicians might be struggling with changing power structures, so future measures to transform the market should involve them to a larger degree.

How soon will digital endpoints become a cornerstone for future drug development?

Digital technologies are transforming healthcare and will provide the basis for more patient-centric innovation in the pharmaceutical industry. Digital endpoints in clinical studies have the potential to drive innovation and reduce costly late-stage failures. This is also currently under consideration by regulatory agencies, such as the US Food and Drug Administration (FDA). The academic-industrial collaboration MOBILISED-D aims to implement and validate real-world walking speed (RWS) as a digital endpoint accepted by regulatory authorities as a first of its class. Previous work has shown that loss of mobility driven by chronic illness and frailty in older patients can be a relevant readout or effect of different diseases and various organ systems.

Digital Transformation and Disruption of the Health Care Sector: Internet-Based Observational Study.

BACKGROUND: Digital innovation, introduced across many industries, is a strong force of transformation. Some industries have seen faster transformation, whereas the health care sector only recently came into focus. A context where digital corporations move into health care, payers strive to keep rising costs at bay, and longer-living patients desire continuously improved quality of care points to a digital and value-based transformation with drastic implications for the health care sector. OBJECTIVE: We tried to operationalize the discussion within the health care sector around digital and disruptive innovation to identify what type of technological enablers, business models, and value networks seem to be emerging from different groups of innovators with respect to their digital transformational efforts. METHODS: From the Forbes 2000 and CBinsights databases, we identified 100 leading technology, life science, and start-up companies active in the health care sector. Further analysis identified projects from these companies within a digital context that were subsequently evaluated using the following criteria: delivery of patient value, presence of a comprehensive and distinctive underlying business model, solutions provided, and customer needs addressed. RESULTS: Our methodological approach recorded more than 400 projects and collaborations. We identified patterns that show established corporations rely more on incremental innovation that supports their current business models, while start-ups engage their flexibility to explore new market segments with notable transformations of established business models. Thereby, start-ups offer higher promises of disruptive innovation. Additionally, start-ups offer more diversified value propositions addressing broader areas of the health care sector. CONCLUSIONS: Digital transformation is an opportunity to accelerate health care performance by lowering cost and improving quality of care. At an economic scale, business models can be strengthened and disruptive innovation models enabled. Corporations should look for collaborations with start-up companies to keep investment costs at bay and off the balance sheet. At the same time, the regulatory knowledge of established corporations might help start-ups to kick off digital disruption in the health care sector.

New digital adherence devices could prevent millions of strokes from atrial fibrillation by the end of the next century.

The effectiveness and safety of a pharmacologic intervention is highly dependent on patient's capability to follow the recommended treatment regimen. Non-adherence to pharmacologic treatments is associated with worsening conditions including hospitalization and death. This is a significant burden to healthcare systems on a global scale with non-adherence rates being as high (or higher) as 50% in the first treatment year. The most common causes for non-adherence are forgetfulness, busy lifestyle or complexity and changes in therapeutic schedules. In conditions like atrial fibrillation (AFib) this leads to a drastic increase in event rates, e.g. strokes. Patients diagnosed with AFib are strongly recommended to receive anticoagulant treatments for stroke prevention. Treatments with Vitamin K antagonists or novel oral anticoagulants (NOACs) can dramatically lower the risk of ischemic strokes in the presence of AFib. Non-adherence can expose the patients to an increased stroke risk. This is especially true for NOACs, due to their short half-life. Patients have to take these medications once or twice daily for adequate stroke prevention, i.e., single non-use of the medication can already diminish or reset the anticoagulative effect. Adherence devices could help improve patient's compliance by reminder or feedback function. They have shown to be successful in a number of clinical trails. Especially, newer devices that make use of digital technologies show promising results but are not used broadly in clinical practice. Here we provide evidence for our hypothesis that newly available adherence devices might increase adherence rates and thereby reduce the number of strokes in patients with AFib.

Demanding response time requirements on coherent receivers due to fast polarization rotations caused by lightning events.

Lightning events can cause fast polarization rotations and phase changes in optical transmission fibers due to strong electrical currents and magnetic fields. Whereas these are unlikely to affect legacy transmission systems with direct detection, different mechanisms have to be considered in systems with local oscillator based coherent receivers and digital signal processing. A theoretical analysis reveals that lightning events can result in polarization rotations with speeds as fast as a few hundred kRad/s. We discuss possible mechanisms how such lightning events can affect coherent receivers with digital signal processing. In experimental investigations with a high current pulse generator and transponder prototypes, we observed post FEC errors after polarization rotation events which can be expected from lightning strikes.

A frequency comb in the extreme ultraviolet.

Since 1998, the interaction of precision spectroscopy and ultrafast laser science has led to several notable accomplishments. Femtosecond laser optical frequency 'combs' (evenly spaced spectral lines) have revolutionized the measurement of optical frequencies and enabled optical atomic clocks. The same comb techniques have been used to control the waveform of ultrafast laser pulses, which permitted the generation of single attosecond pulses, and have been used in a recently demonstrated 'oscilloscope' for light waves. Here we demonstrate intra-cavity high harmonic generation in the extreme ultraviolet, which promises to lead to another joint frontier of precision spectroscopy and ultrafast science. We have generated coherent extreme ultraviolet radiation at a repetition frequency of more than 100 MHz, a 1,000-fold improvement over previous experiments. At such a repetition rate, the mode spacing of the frequency comb, which is expected to survive the high harmonic generation process, is large enough for high resolution spectroscopy. Additionally, there may be many other applications of such a quasi-continuous compact and coherent extreme ultraviolet source, including extreme ultraviolet holography, microscopy, nanolithography and X-ray atomic clocks.