Epidemiology of healthcare-associated Pseudomonas aeruginosa in intensive care units: are sink drains to blame?

BACKGROUND: Pseudomonas aeruginosa (PA) is a common cause of healthcare-associated infection (PA-HAI) in the intensive care unit (ICU). AIM: To describe the epidemiology of PA-HAI in ICUs in Ontario, Canada, and to identify episodes of sink-to-patient PA transmission. METHODS: This was a prospective cohort study of patients in six ICUs from 2018 to 2019, with retrieval of PA clinical isolates, and PA-screening of antimicrobial-resistant organism surveillance rectal swabs, and of sink drain, air, and faucet samples. All PA isolates underwent whole-genome sequencing. PA-HAI was defined using US National Healthcare Safety Network criteria. ICU-acquired PA was defined as PA isolated from specimens obtained ≥48 h after ICU admission in those with prior negative rectal swabs. Sink-to-patient PA transmission was defined as ICU-acquired PA with close genomic relationship to isolate(s) previously recovered from sinks in a room/bedspace occupied 3-14 days prior to collection date of the relevant patient specimen. FINDINGS: Over ten months, 72 PA-HAIs occurred among 60/4263 admissions. The rate of PA-HAI was 2.40 per 1000 patient-ICU-days; higher in patients who were PA-colonized on admission. PA-HAI was associated with longer stay (median: 26 vs 3 days uninfected; P < 0.001) and contributed to death in 22/60 cases (36.7%). Fifty-eight admissions with ICU-acquired PA were identified, contributing 35/72 (48.6%) PA-HAIs. Four patients with five PA-HAIs (6.9%) had closely related isolates previously recovered from their room/bedspace sinks. CONCLUSION: Nearly half of PA causing HAI appeared to be acquired in ICUs, and 7% of PA-HAIs were associated with sink-to-patient transmission. Sinks may be an under-recognized reservoir for HAIs.

Difficulties and challenges experienced by nurses in eldercare institutions in Albania: A qualitative content analysis.

INTRODUCTION: The global and Albanian populations of elderly people are steadily increasing. It is estimated that the number of elderly adults requiring care in Albania will rise from 90.9 thousand to 130.4 thousand by 2030. Despite the envisaged increase in the number and life expectancy of the elderly population in Albania, which will result in an increased demand for nursing care, little is known about the difficulties and challenges that nurses face while providing care for elderly Albanian individuals. AIM: To explore the difficulties and challenges nurses experience while caring for elderly people in Albanian eldercare institutions. METHODS: The study employed a qualitative design using purposive sampling of 20 nurses in 8 eldercare institutions who participated in face-to-face semi-structured interviews. The audio-recorded interviews were transcribed and subsequently subjected to analysis using Graneheim and Lundman's qualitative conventional content analysis. Data analysis was supported by the qualitative data analysis software MAXQDA 2020. The reporting of this study followed the consolidated criteria for reporting qualitative research (COREQ) checklist. RESULTS: Five key categories emerged from data analysis: (1) professional difficulties, (2) educational difficulties, (3) relationship challenges, (4) increased mental stress, and (5) participation in advocacy. This study showed that nursing staff experienced many barriers, challenges, and unmet needs when implementing care for elderly people in long-term care facilities. CONCLUSION: The findings indicate that nurses working in eldercare institutions faced significant challenges in caring for elderly people. Nurses need more legal, financial, educational, and emotional support. The study indicates that more organizational and national support is necessary for nursing staff to care for elderly people in eldercare Albanian institutions properly. Eldercare institution leaders need to recognize the importance of their role in overcoming the barriers and providing adequate support for their staff in caring for elderly people.

Avapritinib-based SAR studies unveil a binding pocket in KIT and PDGFRA.

Avapritinib is the only potent and selective inhibitor approved for the treatment of D842V-mutant gastrointestinal stromal tumors (GIST), the most common primary mutation of the platelet-derived growth factor receptor α (PDGFRA). The approval was based on the NAVIGATOR trial, which revealed overall response rates of more than 90%. Despite this transformational activity, patients eventually progress, mostly due to acquired resistance mutations or following discontinuation due to neuro-cognitive side effects. These patients have no therapeutic alternative and face a dismal prognosis. Notable, little is known about this drug's binding mode and its medicinal chemistry development, which is instrumental for the development of the next generation of drugs. Against this background, we solve the crystal structures of avapritinib in complex with wild-type and mutant PDGFRA and stem cell factor receptor (KIT), which provide evidence and understanding of inhibitor binding and lead to the identification of a sub-pocket (Gα-pocket). We utilize this information to design, synthesize and characterize avapritinib derivatives for the determination of key pharmacophoric features to overcome drug resistance and limit potential blood-brain barrier penetration.

Prospective monitoring of adverse events following vaccination with Modified vaccinia Ankara - Bavarian Nordic (MVA-BN) administered to a Canadian population at risk of Mpox: A Canadian Immunization Research Network study.

MVA-BN is an orthopoxvirus vaccine that provides protection against both smallpox and mpox. In June 2022, Canada launched a publicly-funded vaccination campaign to offer MVA-BN to at-risk populations including men who have sex with men (MSM) and sex workers. The safety of MVA-BN has not been assessed in this context. To address this, the Canadian National Vaccine Safety Network (CANVAS) conducted prospective safety surveillance during public health vaccination campaigns in Toronto, Ontario and in Vancouver, British Columbia. Vaccinated participants received a survey 7 and 30 days after each MVA-BN dose to elicit adverse health events. Unvaccinated individuals from a concurrent vaccine safety project evaluating COVID-19 vaccine safety were used as controls. Vaccinated and unvaccinated participants that reported a medically attended visit on their 7-day survey were interviewed. Vaccinated participants and unvaccinated controls were matched 1:1 based on age group, gender, sex and provincial study site. Overall, 1,173 vaccinated participants completed a 7-day survey, of whom 75 % (n = 878) also completed a 30-day survey. Mild to moderate injection site pain was reported by 60 % of vaccinated participants. Among vaccinated participants 8.4 % were HIV positive and when compared to HIV negative vaccinated individuals, local injection sites were less frequent in those with HIV (48 % vs 61 %, p = 0.021), but health events preventing work/school or requiring medical assessment were more frequent (7.1 % vs 3.1 %, p = 0.040). Health events interfering with work/school, or requiring medical assessment were less common in the vaccinated group than controls (3.3 % vs. 7.1 %, p < 0.010). No participants were hospitalized within 7 or 30 days of vaccination. No cases of severe neurological disease, skin disease, or myocarditis were identified. Our results demonstrate that the MVA-BN vaccine appears safe when used for mpox prevention, with a low frequency of severe adverse events and no hospitalizations observed.

The value of sonographic microvascular imaging in the diagnosis of lipedema.

BACKGROUND: Lipedema is a chronic disease marked by symmetric enlargement of painful nodular and fibrotic adipose tissue, predominantly affecting the limbs. Since there is no specific test or biomarker for this condition, years often pass before the diagnosis of lipedema is established for the first time, thereby causing psychosocial distress, including depression, eating disorders, and social isolation. Over the last few years several advanced Doppler-based technologies have been developed to visualize slow flow blood vessels and superficial microvascular architecture undetectable by traditional color Doppler flow imaging (CDFI). OBJECTIVE: The aim of this study was to evaluate the superficial microvascular anatomy in lipedema patients compared to healthy controls and investigate the clinical significance of the Ultra Micro Angiography (UMA) technology in the diagnosis of lipedema. This new technique may contribute to reduce the diagnostic delay and, eventually, establish and guide treatment strategies toward a better therapeutic outcome in lipedema patients. METHODS: 25 patients with lipedema and ten healthy controls with no history of lipedema were included in this study. All ultrasound examinations were performed on a novel high-performance ultrasound system (Resona R9/Mindray) using CDFI and the UMA technique. RESULTS: In all of the patients, Ultra Micro Angiography achieved the excellent visualization of microvascular structures, revealing that most lipedema patients showed grade 3 (n = 13) or grade 2 (n = 8) flow. UMA was superior to CDFI for depicting the microvascular structures. CONCLUSIONS: Here we show that UMA imaging characterizes the subcutaneous microvasculature with an unprecedented accuracy. The method has the advantage of being sensitive to small, slow-flowing vessels. This allows for the assessment of the course of vessels and vascular pathologies in great detail. Thus, UMA as a non-invasive diagnostic method can improve diagnostic accuracy in lipedema.

Designing the stripe-ordered cuprate phase diagram through uniaxial-stress.

The ability to efficiently control charge and spin in the cuprate high-temperature superconductors is crucial for fundamental research and underpins technological development. Here, we explore the tunability of magnetism, superconductivity, and crystal structure in the stripe phase of the cuprate La[Formula: see text]Ba[Formula: see text]CuO[Formula: see text], with [Formula: see text] = 0.115 and 0.135, by employing temperature-dependent (down to 400 mK) muon-spin rotation and AC susceptibility, as well as X-ray scattering experiments under compressive uniaxial stress in the CuO[Formula: see text] plane. A sixfold increase of the three-dimensional (3D) superconducting critical temperature [Formula: see text] and a full recovery of the 3D phase coherence is observed in both samples with the application of extremely low uniaxial stress of [Formula: see text]0.1 GPa. This finding demonstrates the removal of the well-known 1/8-anomaly of cuprates by uniaxial stress. On the other hand, the spin-stripe order temperature as well as the magnetic fraction at 400 mK show only a modest decrease under stress. Moreover, the onset temperatures of 3D superconductivity and spin-stripe order are very similar in the large stress regime. However, strain produces an inhomogeneous suppression of the spin-stripe order at elevated temperatures. Namely, a substantial decrease of the magnetic volume fraction and a full suppression of the low-temperature tetragonal structure is found under stress, which is a necessary condition for the development of the 3D superconducting phase with optimal [Formula: see text]. Our results evidence a remarkable cooperation between the long-range static spin-stripe order and the underlying crystalline order with the three-dimensional fully coherent superconductivity. Overall, these results suggest that the stripe- and the SC order may have a common physical mechanism.

Reporting standard for describing first responder systems, smartphone alerting systems, and AED networks.

Standardized reporting of data is crucial for out-of-hospital cardiac arrest (OHCA) research. While the implementation of first responder systems dispatching volunteers to OHCA is encouraged, there is currently no uniform reporting standard for describing these systems. A steering committee established a literature search to identify experts in smartphone alerting systems. These international experts were invited to a conference held in Hinterzarten, Germany, with 40 researchers from 13 countries in attendance. Prior to the conference, participants submitted proposals for parameters to be included in the reporting standard. The conference comprised five workshops covering different aspects of smartphone alerting systems. Proposed parameters were discussed, clarified, and consensus was achieved using the Nominal Group Technique. Participants voted in a modified Delphi approach on including each category as a core or supplementary element in the reporting standard. Results were presented, and a writing group developed definitions for all categories and items, which were sent to participants for revision and final voting using LimeSurvey web-based software. The resulting reporting standard consists of 68 core items and 21 supplementary items grouped into five topics (first responder system, first responder network, technology/algorithm/strategies, reporting data, and automated external defibrillators (AED)). This proposed reporting standard generated by an expert opinion group fills the gap in describing first responder systems. Its adoption in future research will facilitate comparison of systems and research outcomes, enhancing the transfer of scientific findings to clinical practice.

Further Evidence for Shape Coexistence in

Isomers close to doubly magic _{28}^{78}Ni_{50} provide essential information on the shell evolution and shape coexistence near the Z=28 and N=50 double shell closure. We report the excitation energy measurement of the 1/2^{+} isomer in _{30}^{79}Zn_{49} through independent high-precision mass measurements with the JYFLTRAP double Penning trap and with the ISOLTRAP multi-reflection time-of-flight mass spectrometer. We unambiguously place the 1/2^{+} isomer at 942(10) keV, slightly below the 5/2^{+} state at 983(3) keV. With the use of state-of-the-art shell-model diagonalizations, complemented with discrete nonorthogonal shell-model calculations which are used here for the first time to interpret shape coexistence, we find low-lying deformed intruder states, similar to other N=49 isotones. The 1/2^{+} isomer is interpreted as the bandhead of a low-lying deformed structure akin to a predicted low-lying deformed band in ^{80}Zn, and points to shape coexistence in ^{79,80}Zn similar to the one observed in ^{78}Ni. The results make a strong case for confirming the claim of shape coexistence in this key region of the nuclear chart.

The added value of daily diary data in 1- and 3-year prediction of psychopathology and psychotic experiences in individuals at risk for psychosis.

This study aimed to assess whether adding information on psychological experiences derived from a daily diary to baseline cross-sectional data could improve short- (1-year) and long-term (3-years) prediction of psychopathology and positive psychotic experiences (PEs). We used 90-day daily diary data from 96 individuals in early subclinical risk stages for psychosis. Stepwise linear regression models were built for psychopathology and PEs at 1- and 3-years follow-up, adding: (1) baseline questionnaires, (2) the mean and variance of daily psychological experiences, and (3) individual symptom network density. We assessed whether similar results could be achieved with a subset of the data (7-14- and 30-days). The mean and variance of the diary improved model prediction of short- and long-term psychopathology and PEs, compared to prediction based on baseline questionnaires solely. Similar results were achieved with 7-14- and 30-day subsets. Symptom network density did not improve model prediction except for short-term prediction of PEs. Simple metrics, i.e., the mean and variance from 7 to 14 days of daily psychological experiences assessments, can improve short- and long-term prediction of both psychopathology and PEs in individuals in early subclinical stages for psychosis. Diary data could be a valuable addition to clinical risk prediction models for psychopathology development.

[Clavicle fractures: practical approach in clinical routine]. / Klavikulafrakturen ­ praktisches Vorgehen im klinischen Alltag.

Fractures of the clavicle are among the most common fractures. They typically result from a fall onto the lateral shoulder or the extended arm and are often related to sports and bicycle accidents. Obtaining the exact trauma mechanism, proper clinical findings and adequate X­rays usually lead to the correct diagnosis. Non-displacement fractures can be treated conservatively with good results. Unstable and displaced fractures should be treated operatively. Open fractures or looming penetration are emergencies und should be treated immediately. In addition to fracture classification and morphology, other factors such as additional injuries and patient-related factors need to be considered in order to make an individualized therapy decision. In operative treatment, angular stable plating is the therapy of choice, and in most cases early functional aftercare is possible.

Impact of Anxiety During Hospitalization on the Clinical Outcome of Patients With Osteoporotic Thoracolumbar Vertebral Fracture.

STUDY DESIGN: Multicenter prospective cohort study. OBJECTIVES: Anxiety in combination with osteoporotic vertebral compression fractures (OVCFs) of the spine remains understudied. The purpose of this study was to analyze whether anxiety has an impact on the short-term functional outcome of patients with an OVCF. Furthermore, a direct impact of the fracture on the patient's anxiety during hospitalization should be recognized. METHODS: All inpatients with an OVCF of the thoracolumbar spine from 2017 to 2020 were included. Trauma mechanism, analgetic medication, anti-osteoporotic therapy, timed-up-and-go test (TuG), mobility, Barthel index, Oswestry-Disability Index (ODI) and EQ5D-5L were documented.For statistical analysis, the U test, chi-square independence test, Spearman correlation, General Linear Model for repeated measures, Bonferroni analysis and Wilcoxon test were used. The item anxiety/depression of the EQ5D-5L was analyzed to describe the patients' anxiousness. RESULTS: Data from 518 patients from 17 different hospitals were evaluated. Fracture severity showed a significant correlation (r = .087, P = .0496) with anxiety. During the hospital stay, pain medication (P < .001), anti-osteoporotic medication (P < .001), and initiation of surgical therapy (P < .001) were associated with less anxiety. The anxiety of a patient at discharge was negatively related to the functional outcomes at the individual follow-up: TuG (P < .001), Barthel index (P < .001), ODI (P < .001) and EQ5D-5L (P < .001). CONCLUSIONS: Higher anxiety is associated with lower functional outcome after OVCF. The item anxiety/depression of the EQ5D-5L provides an easily accessible, quick and simple tool that can be used to screen for poor outcomes and may also offer the opportunity for a specific anxiety intervention.

Universal magnetic proximity effect in ferromagnet-semiconductor quantum well hybrid structures.

Hybrid ferromagnet-semiconductor systems possess new outstanding properties, which emerge when bringing magnetic and semiconductor materials into contact. In such structures, the long-range magnetic proximity effect couples the spin systems of the ferromagnet and semiconductor on distances exceeding the carrier wave function overlap. The effect is due to the effective p-d exchange interaction of acceptor-bound holes in the quantum well with d-electrons of the ferromagnet. This indirect interaction is established via the phononic Stark effect mediated by the chiral phonons. Here, we demonstrate that the long-range magnetic proximity effect is universal and observed in hybrid structures with diverse magnetic components and potential barriers of various thicknesses and compositions. We study hybrid structures consisting of a semimetal (magnetite Fe3O4) or dielectric (spinel NiFe2O4) ferromagnet and a CdTe quantum well separated by a nonmagnetic (Cd,Mg)Te barrier. The proximity effect is manifested in the circular polarization of the photoluminescence corresponding to the recombination of photoexcited electrons with holes bound to shallow acceptors in the quantum well induced by magnetite or spinel itself, in contrast to interface ferromagnet in case of metal-based hybrid systems. A nontrivial dynamics of the proximity effect is observed in the studied structures due to recombination-induced dynamic polarization of electrons in the quantum well. It enables the determination of the exchange constant Δexch ≈ 70 µeV in a magnetite-based structure. The universal origin of the long-range exchange interaction along with the possibility of its electrical control offers prospects for the development of low-voltage spintronic devices compatible with existing solid-state electronics.

Atypical presentations and pitfalls of achalasia.

Achalasia is a rare disease with significant diagnostic delay and association with false diagnoses and unnecessary interventions. It remains unclear, whether atypical presentations, misinterpreted symptoms or inconclusive diagnostics are the cause. The aim of this study was the characterization of typical and atypical features of achalasia and their impact on delays, misinterpretations or false diagnoses. A retrospective analysis of prospective database over a period of 30 years was performed. Data about symptoms, delays and false diagnoses were obtained and correlated with manometric, endoscopic and radiologic findings. Totally, 300 patients with achalasia were included. Typical symptoms (dysphagia, regurgitation, weight loss and retrosternal pain) were present in 98.7%, 88%, 58.4% and 52.4%. The mean diagnostic delay was 4.7 years. Atypical symptoms were found in 61.7% and led to a delay of 6 months. Atypical gastrointestinal symptoms were common (43%), mostly 'heartburn' (16.3%), 'vomiting' (15.3%) or belching (7.7%). A single false diagnosis occurred in 26%, multiple in 16%. Major gastrointestinal misdiagnoses were GERD in 16.7% and eosinophilic esophagitis in 4%. Other false diagnosis affected ENT-, psychiatric, neurologic, cardiologic or thyroid diseases. Pitfalls were the description of 'heartburn' or 'nausea'. Tertiary contractions at barium swallows, hiatal hernias and 'reflux-like' changes at endoscopy or eosinophils in the biopsies were misleading. Atypical symptoms are common in achalasia, but they are not the sole source for diagnostic delays. Misleading descriptions of typical symptoms or misinterpretation of diagnostic studies contribute to false diagnoses and delays.

Can elderly patients regain their preoperative functional level after distal radius fracture type A? Results from a fracture register study using PROM.

Introduction: Although distal radius fractures (DRFs) are the most common fractures of the human body, there are still ongoing debates concerning the treatment for type A fractures, especially in elderly patients. In spite of good clinical outcomes, it remains unclear whether elderly patients, especially, could regain the preoperative functional level of the wrist. Therefore, we have quantified wrist function within a retrospective study design using patient-reported outcome measures (PROM) and we have analyzed the influence of age between control and patient collective and young vs. old, respectively. Patients and methods: The retrospective study included all patients with a surgically treated DRF type A and a control group of healthy patients, age and gender matched. The function of the wrist was examined by using a self-assessment questionnaire called the Munich Wrist Questionnaire (MWQ) according to the patient-related outcome measurements PROM. Results: We could enroll 110 patients and controls, and the average follow-up was 66 months. Subgroup matching induced similar age group distribution: in both groups, 7 individuals <30 years, 67 between 31 and 64 years, 29 between 65 and 79 years, and 7 individuals >80 years, were enrolled, respectively. In the fracture group, women were significantly older than men (59 ± 15 vs. 47 ± 17 (M ± SD). There was no significant difference between the control and the patient groups (96 ± 6 vs. 95 ± 7). The function was significantly different between controls and patients <30 years (100 ± 1 vs. 98 ± 2). In the control group, there was a functional difference in the age group <30 compared with 65-79 and >80 and in the age group 30-64 compared with 65-79 and >80. In the control group, the function was found to be significantly decreasing with advancing age, whereas in the patient group, this influence was absent. A correlation analysis showed a worse function with increasing age in the control group and therefore a negative correlation. In the fracture group, a similar result could not be obtained. Discussion: Age has a relevant influence on wrist function. Although the wrist function decreases significantly with aging, in the patient group, this influence is absent, and the functional results after surgery are excellent. Even elderly patients can regain their preoperative functional level.

[Use of regional anesthesia for preoperative analgesia for proximal femoral fractures in the emergency department : A survey on current practice in German-speaking countries and the United Kingdom]. / Anwendung regionalanästhesiologischer Verfahren zur präoperativen Analgesie bei proximalen Femurfrakturen in der Notaufnahme : Eine Umfrage zur Praxis im deutschsprachigen Raum und in Großbritannien.

BACKGROUND: Regional anesthesia (RA) techniques such as femoral nerve block (FNB) or fascia iliaca compartment block (FICB) are effective analgesia techniques in the treatment of pain from proximal femoral fractures (PFF). While in Great Britain (GB) these are already frequently used in the emergency department for preoperative analgesia, in the German-speaking D­A-CH area (Germany, Austria, Switzerland) this seems to occur much less frequently. Therefore, the aim of this study was to survey the type and frequency of RA procedures used and to compare international practice. MATERIAL AND METHODS: In the D­A-CH area as well as in GB, registered emergency departments were contacted and invited to participate in an online survey. The survey included questions on the frequency and type of RA procedures, reasons for non-use, equipment used, person performing the procedure and medications used. RESULTS: The participation rate was 17.4% (142/818 emergency departments). RA procedures for preoperative analgesia in PFF were used in 18.3% (21/115) of hospitals in the D­A-CH region and in 96.3% (26/27) in GB. The most commonly used block was the FICB in GB at 96.2% (25/26) and the FNB in Germany at 66.7% (14/21). In the D­A-CH area, RA procedures are primarily performed by anesthesiology specialists 71.4% (15/21), and in GB by emergency department residents 65.4% (17/26). DISCUSSION: RA procedures are still performed too rarely following PFF in emergency departments in the D­A-CH area. In international comparison with GB there is potential for improvement.

Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons.

Pathogenic heterozygous variants in SCN2A, which encodes the neuronal sodium channel NaV1.2, cause different types of epilepsy or intellectual disability (ID)/autism without seizures. Previous studies using mouse models or heterologous systems suggest that NaV1.2 channel gain-of-function typically causes epilepsy, whereas loss-of-function leads to ID/autism. How altered channel biophysics translate into patient neurons remains unknown. Here, we investigated iPSC-derived early-stage cortical neurons from ID patients harboring diverse pathogenic SCN2A variants [p.(Leu611Valfs*35); p.(Arg937Cys); p.(Trp1716*)] and compared them with neurons from an epileptic encephalopathy (EE) patient [p.(Glu1803Gly)] and controls. ID neurons consistently expressed lower NaV1.2 protein levels. In neurons with the frameshift variant, NaV1.2 mRNA and protein levels were reduced by ~ 50%, suggesting nonsense-mediated decay and haploinsufficiency. In other ID neurons, only protein levels were reduced implying NaV1.2 instability. Electrophysiological analysis revealed decreased sodium current density and impaired action potential (AP) firing in ID neurons, consistent with reduced NaV1.2 levels. In contrast, epilepsy neurons displayed no change in NaV1.2 levels or sodium current density, but impaired sodium channel inactivation. Single-cell transcriptomics identified dysregulation of distinct molecular pathways including inhibition of oxidative phosphorylation in neurons with SCN2A haploinsufficiency and activation of calcium signaling and neurotransmission in epilepsy neurons. Together, our patient iPSC-derived neurons reveal characteristic sodium channel dysfunction consistent with biophysical changes previously observed in heterologous systems. Additionally, our model links the channel dysfunction in ID to reduced NaV1.2 levels and uncovers impaired AP firing in early-stage neurons. The altered molecular pathways may reflect a homeostatic response to NaV1.2 dysfunction and can guide further investigations.