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"Michael Fischer"
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Appropriateness of outpatient antibiotic prescribing among privately insured US patients: ICD-10-CM based cross sectional study
To assess the appropriateness of outpatient antibiotic prescribing for privately insured children and non-elderly adults in the US using a comprehensive classification scheme of diagnosis codes in ICD-10-CM (international classification of diseases-clinical modification, 10th revision), which replaced ICD-9-CM in the US on 1 October 2015.
Cross sectional study.
MarketScan Commercial Claims and Encounters database, 2016.
19.2 million enrollees aged 0-64 years.
A classification scheme was developed that determined whether each of the 91 738 ICD-10-CM diagnosis codes \"always,\" \"sometimes,\" or \"never\" justified antibiotics. For each antibiotic prescription fill, this scheme was used to classify all diagnosis codes in claims during a look back period that began three days before antibiotic prescription fills and ended on the day fills occurred. The main outcome was the proportion of fills in each of four mutually exclusive categories: \"appropriate\" (associated with at least one \"always\" code during the look back period, \"potentially appropriate\" (associated with at least one \"sometimes\" but no \"always\" codes), \"inappropriate\" (associated only with \"never\" codes), and \"not associated with a recent diagnosis code\" (no codes during the look back period).
The cohort (n=19 203 264) comprised 14 571 944 (75.9%) adult and 9 935 791 (51.7%) female enrollees. Among 15 455 834 outpatient antibiotic prescription fills by the cohort, the most common antibiotics were azithromycin (2 931 242, 19.0%), amoxicillin (2 818 939, 18.2%), and amoxicillin-clavulanate (1 784 921, 11.6%). Among these 15 455 834 fills, 1 973 873 (12.8%) were appropriate, 5 487 003 (35.5%) were potentially appropriate, 3 592 183 (23.2%) were inappropriate, and 4 402 775 (28.5%) were not associated with a recent diagnosis code. Among the 3 592 183 inappropriate fills, 2 541 125 (70.7%) were written in office based settings, 222 804 (6.2%) in urgent care centers, and 168 396 (4.7%) in emergency departments. In 2016, 2 697 918 (14.1%) of the 19 203 264 enrollees filled at least one inappropriate antibiotic prescription, including 490 475 out of 4 631 320 children (10.6%) and 2 207 173 out of 14 571 944 adults (15.2%).
Among all outpatient antibiotic prescription fills by 19 203 264 privately insured US children and non-elderly adults in 2016, 23.2% were inappropriate, 35.5% were potentially appropriate, and 28.5% were not associated with a recent diagnosis code. Approximately 1 in 7 enrollees filled at least one inappropriate antibiotic prescription in 2016. The classification scheme could facilitate future efforts to comprehensively measure outpatient antibiotic appropriateness in the US, and it could be adapted for use in other countries that use ICD-10 codes.
Journal Article
Handbook of critical policy studies
Critical policy studies, as illustrated in this handbook, challenges the conventional approaches of public policy inquiry. But it offers important innovations as well, in particular its focus on discursive politics, policy argumentation and deliberation and interpretive modes of analysis. This volume offers a compilation of critical work that assesses past developments and appraises emerging issues.
Book
Nobel somatosensations and pain
The Nobel prices 2021 for Physiology and Medicine have been awarded to David Julius and Ardem Patapoutian \"for their discoveries of receptors for temperature and touch\", TRPV1 and PIEZO1/2. The present review tells the past history of the capsaicin receptor, covers further selected TRP channels, TRPA1 in particular, and deals with mechanosensitivity in general and mechanical hyperalgesia in particular. Other achievements of the laureates and translational aspects of their work are shortly treated.
Journal Article
Sensitization of TRPA1 by Protein Kinase A
The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.
Journal Article
First-Principles Study of AlPO4-H3, a Hydrated Aluminophosphate Zeotype Containing Two Different Types of Adsorbed Water Molecules
Porous aluminophosphate zeotypes (AlPOs) are promising materials for heat transformation applications using water as a working fluid. Two “types” of adsorbed water molecules can be distinguished in hydrated AlPOs: Water molecules adsorbed in the direct proximity of framework aluminium atoms form bonds to these Al atoms, with the coordination number of Al increasing from four to five or six. The remaining water molecules that are adsorbed in other parts of the accessible pore space are not strongly bonded to any framework atom, they interact with their environment exclusively through hydrogen bonds. The APC-type small-pore aluminophosphate AlPO4-H3 contains both types of H2O molecules. In the present work, this prototypical hydrated AlPO is studied using dispersion-corrected density functional theory (DFT) calculations. After validating the computations against experimental crystal structure and Raman spectroscopy data, three interrelated aspects are addressed: First, calculations for various partially hydrated models are used to establish that such partially hydrated phases are not thermodynamically stable, as the interaction with the adsorbed water molecules is distinctly weaker than in fully hydrated AlPO4-H3. Second, IR and Raman spectra are computed and compared to those of the dehydrated analogue AlPO4-C, leading to the identification of a few “fingerprint” modes that could be used as indicators for the presence of Al-coordinated water molecules. Finally, DFT-based molecular dynamics calculations are employed to study the dynamics of the adsorbed water molecules. All in all, this in-depth computational study of AlPO4-H3 contributes to the fundamental understanding of hydrated AlPOs, and should therefore provide valuable information for future computational and experimental studies of these systems.
Journal Article
Cultured rat aortic vascular smooth muscle cells do not express a functional TRPV1
We showed previously that capsaicin, an active compound of chili peppers, can inhibit platelet-derived growth factor-induced proliferation in primary rat vascular smooth muscle cells (VSMCs). The inhibition of BrdU incorporation by capsaicin in these cells was revoked by BCTC, which might be explained by a role of TRPV1 in VSMCs proliferation. To further pursue the hypothesis of a TRPV1-dependent effect of capsaicin, we investigated TRPV1 expression and function. Commercially available antibodies against two different TRPV1 epitopes (N-terminus and C-terminus) were rendered invalid in detecting TRPV1, as shown: i) in western blot experiments using control lysates of TRPV1-expressing (PC-12 and hTRPV1 transfected HEK293T) and TRPV1-downregulated (CRISPR/Cas gene edited A10) cells, and ii) by substantial differences in staining patterns between the applied antibodies using fluorescence confocal microscopy. The TRPV1 agonists capsaicin, resiniferatoxin, piperine and evodiamine did not increase intracellular calcium levels in primary VSMCs and in A10 cells. Using RT qPCR, we could detect a rather low TRPV1 expression in VSMCs at the mRNA level (Cp value around 30), after validating the primer pair in NGF-stimulated PC-12 cells. We conclude that rat vascular smooth muscle cells do not possess canonical TRPV1 channel activity, which could explain the observed antiproliferative effect of capsaicin.
Journal Article
Th2 Modulation of Transient Receptor Potential Channels: An Unmet Therapeutic Intervention for Atopic Dermatitis
Atopic dermatitis (AD) is a multifaceted, chronic relapsing inflammatory skin disease that affects people of all ages. It is characterized by chronic eczema, constant pruritus, and severe discomfort. AD often progresses from mild annoyance to intractable pruritic inflammatory lesions associated with exacerbated skin sensitivity. The T helper-2 (Th2) response is mainly linked to the acute and subacute phase, whereas Th1 response has been associated in addition with the chronic phase. IL-17, IL-22, TSLP, and IL-31 also play a role in AD. Transient receptor potential (TRP) cation channels play a significant role in neuroinflammation, itch and pain, indicating neuroimmune circuits in AD. However, the Th2-driven cutaneous sensitization of TRP channels is underappreciated. Emerging findings suggest that critical Th2-related cytokines cause potentiation of TRP channels, thereby exaggerating inflammation and itch sensation. Evidence involves the following: (i) IL-13 enhances TRPV1 and TRPA1 transcription levels; (ii) IL-31 sensitizes TRPV1 via transcriptional and channel modulation, and indirectly modulates TRPV3 in keratinocytes; (iii) The Th2-cytokine TSLP increases TRPA1 synthesis in sensory neurons. These changes could be further enhanced by other Th2 cytokines, including IL-4, IL-25, and IL-33, which are inducers for IL-13, IL-31, or TSLP in skin. Taken together, this review highlights that Th2 cytokines potentiate TRP channels through diverse mechanisms under different inflammatory and pruritic conditions, and link this effect to distinct signaling cascades in AD. This review strengthens the notion that interrupting Th2-driven modulation of TRP channels will inhibit transition from acute to chronic AD, thereby aiding the development of effective therapeutics and treatment optimization.
Journal Article
Artificial Intelligence in Medicine: Cross-Sectional Study Among Medical Students on Application, Education, and Ethical Aspects
The use of artificial intelligence (AI) in medicine not only directly impacts the medical profession but is also increasingly associated with various potential ethical aspects. In addition, the expanding use of AI and AI-based applications such as ChatGPT demands a corresponding shift in medical education to adequately prepare future practitioners for the effective use of these tools and address the associated ethical challenges they present.
This study aims to explore how medical students from Germany, Austria, and Switzerland perceive the use of AI in medicine and the teaching of AI and AI ethics in medical education in accordance with their use of AI-based chat applications, such as ChatGPT.
This cross-sectional study, conducted from June 15 to July 15, 2023, surveyed medical students across Germany, Austria, and Switzerland using a web-based survey. This study aimed to assess students' perceptions of AI in medicine and the integration of AI and AI ethics into medical education. The survey, which included 53 items across 6 sections, was developed and pretested. Data analysis used descriptive statistics (median, mode, IQR, total number, and percentages) and either the chi-square or Mann-Whitney U tests, as appropriate.
Surveying 487 medical students across Germany, Austria, and Switzerland revealed limited formal education on AI or AI ethics within medical curricula, although 38.8% (189/487) had prior experience with AI-based chat applications, such as ChatGPT. Despite varied prior exposures, 71.7% (349/487) anticipated a positive impact of AI on medicine. There was widespread consensus (385/487, 74.9%) on the need for AI and AI ethics instruction in medical education, although the current offerings were deemed inadequate. Regarding the AI ethics education content, all proposed topics were rated as highly relevant.
This study revealed a pronounced discrepancy between the use of AI-based (chat) applications, such as ChatGPT, among medical students in Germany, Austria, and Switzerland and the teaching of AI in medical education. To adequately prepare future medical professionals, there is an urgent need to integrate the teaching of AI and AI ethics into the medical curricula.
Journal Article
M2 Polarization of Human Macrophages Favors Survival of the Intracellular Pathogen Chlamydia pneumoniae
Intracellular pathogens have developed various strategies to escape immunity to enable their survival in host cells, and many bacterial pathogens preferentially reside inside macrophages, using diverse mechanisms to penetrate their defenses and to exploit their high degree of metabolic diversity and plasticity. Here, we characterized the interactions of the intracellular pathogen Chlamydia pneumoniae with polarized human macrophages. Primary human monocytes were pre-differentiated with granulocyte macrophage colony-stimulating factor or macrophage colony-stimulating factor for 7 days to yield M1-like and M2-like macrophages, which were further treated with interferon-γ and lipopolysaccharide or with interleukin-4 for 48 h to obtain fully polarized M1 and M2 macrophages. M1 and M2 cells exhibited distinct morphology with round or spindle-shaped appearance for M1 and M2, respectively, distinct surface marker profiles, as well as different cytokine and chemokine secretion. Macrophage polarization did not influence uptake of C. pneumoniae, since comparable copy numbers of chlamydial DNA were detected in M1 and M2 at 6 h post infection, but an increase in chlamydial DNA over time indicating proliferation was only observed in M2. Accordingly, 72±5% of M2 vs. 48±7% of M1 stained positive for chlamydial lipopolysaccharide, with large perinuclear inclusions in M2 and less clearly bordered inclusions for M1. Viable C. pneumoniae was present in lysates from M2, but not from M1 macrophages. The ability of M1 to restrict chlamydial replication was not observed in M1-like macrophages, since chlamydial load showed an equal increase over time for M1-like and M2-like macrophages. Our findings support the importance of macrophage polarization for the control of intracellular infection, and show that M2 are the preferred survival niche for C. pneumoniae. M1 did not allow for chlamydial proliferation, but failed to completely eliminate chlamydial infection, giving further evidence for the ability of C. pneumoniae to evade cellular defense and to persist in human macrophages.
Journal Article