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Patient expectations of receiving antibiotics for common symptoms can trigger unnecessary use. We conducted a survey (n = 564) between January 2020 to June 2021 in public and private primary care clinics in Texas to study the prevalence and predictors of patients' antibiotic expectations for common symptoms/illnesses. We surveyed Black patients (33%) and Hispanic/Latine patients (47%), and over 93% expected to receive an antibiotic for at least 1 of the 5 pre-defined symptoms/illnesses. Public clinic patients were nearly twice as likely to expect antibiotics for sore throat, diarrhea, and cold/flu than private clinic patients. Lack of knowledge of potential risks of antibiotic use was associated with increased antibiotic expectations for diarrhea (odds ratio [OR] = 1.6; 95% CI, 1.1-2.4) and cold/flu symptoms (OR = 2.9; 95% CI, 2.0-4.4). Lower education and inadequate health literacy were predictors of antibiotic expectations for diarrhea. Future antibiotic stewardship interventions should tailor patient education materials to include information on antibiotic risks and guidance on appropriate antibiotic indications. Key words: antibiotic use; antimicrobial stewardship; primary care; antibiotic risks; patient expectations, https://doi.org/10.1370/afm.3161 INTRODUCTION Patients often receive antibiotic prescriptions to treat common viral symptoms/ illnesses, such as respiratory tract infection, (1-6) cold/flu, (7,8) and diarrhea, (9,10) despite guidelines recommending against these practices. [...]

This study examines hydrophobic surface coatings for stimulation electrodes to mitigate foreign body reactions and encapsulation. Electrospinning of polydimethylsiloxane (PDMS) resin is explored to create fiber structures for electrode coatings. PDMS resin is succesfully processed into fiber mats. Electrospun PDMS fiber structures showed an increased water contact angle (124 °/125 °) in comparison to a cast flat film (102 °). To further increase hydrophobicity, the fabrication process of Slippery Liquid-Infused Porous Surface (SLIPS) systems with a polyurethane substrate and different natural lubricants is assessed with promising results in an increase in water contact angles up to 11°. The findings suggest the potential of these surface coatings to enhance the performance and safety of stimulation electrodes.

This article examines Gjellestad as one of many archaeological sites containing ship burials. These burial sites are our most important source of information about boats and ships in the Late Iron Age. They also shed light on religious practices and reveal past power distribution and the political dynamics of their contemporary society. Instead of focusing solely on Gjellestad as an example of such an archaeological context, the article goes through the entire inventory of ship burials from the Nordic countries, as well as relevant examples from beyond this core region. The focus here is on ship mounds as political messengers; the chapter demonstrates that ship burials were primarily a phenomenon of the Viking Age and clearly indicate a burial practice associated with the elite and ruling class of society. Ship burials were placed in local centres of power, areas that must have held central functions in terms of long-distance trade, political administration, and the exercise of power.

The spark that ignited this research project was the discovery of the Gjellestad ship in the autumn of 2018 by the Norwegian Institute for Cultural Heritage Research (NIKU). The surveying was initiated by Østfold County Council (ØCC) after a landowner planned to drain farmland (Figure 1). Archaeologists Lars Gustavsen and Erich Nau, both associated with NIKU, conducted the geophysical surveys that led to the uncovering of this amazing archaeological find. The discovery attracted massive international interest, partly because in this particular landscape in Østfold County no one had ever found any evidence to suggest that a ship could be hidden below the ground – this “ship” was considered something of an anomaly. In 2019 the Directorate for Cultural Heritage (Riksantikvaren) funded the verification project to investigate the degree of preservation of the ship anomaly using Ground Penetrating Radar (GPR), as well as to collect material for radiocarbon-dating of other features detected with the GPR. The Museum of Cultural History (MCH) at the University of Oslo led investigations of the ship anomaly, while ØCC led the remaining part of the surveying, mainly through trial trenching and sampling. MCH’s investigations showed that the ship’s state of preservation was poor, with the remaining wood both fragile and prone to attacks from soft rot bacteria, causing uncontrolled deterioration. On the advice of the cultural heritage authorities, the government decided to cover the full cost of the excavation of the ship burial. This excavation was conducted in 2020-21 under the leadership of archaeologist Christian Løchsen Rødsrud.

IntroductionEustachian tube dysfunction can cause inadequate ventilation of the middle ear and is therefore one of the main reasons for the development of chronic middle ear infections. This can significantly impact the quality of life. There is a variety of treatment options, but in most cases long-term success is limited. For this reason, stenting the Eustachian tube (ET) may be a safe and effective alternative. Biodegradable stents have been developed that support the impaired ET function until natural ventilation of the middle ear via the ET is restored, and dissolve after their function has been fulfilled.ObjectiveThe purpose of the current study was to investigate feasibility of implantation and degradation kinetics of biodegradable polymer stents in the ET.Study designThe study was set up as an orientation study.MethodsBiodegradable stents (diameter: 3.5 mm; length: 15 mm) were made from Poly-L-lactic acid (PLLA) in a dip-coating process and subsequent laser cutting and were crimped on a balloon catheter. Stent implantation into the ET was performed unilaterally in nine healthy female blackface sheep under endoscopic control with a dedicated insertion tool and an inflation pressure of 10 bar for 2 min. Ventilation of the middle ear was controlled by tympanometry weekly throughout the observation period of 3, 6, or 12 months (three animals each). After the final examination, cone beam computed tomography scans and histological examinations of the ETs were performed.ResultsAll stents could be inserted as planned. Pharyngeal orifices of all sheep were closed at half-time and final follow-up inspections. After 3 months, all stents were functional, but already showed first fragment formation. Six months after insertion, the stents had largely collapsed but still held open a residual lumen and after 12 months, the ETs were completely collapsed close to their natural shape. Fragments of various sizes were found distributed in the tissue beneath an epithelialized ET.ConclusionThe polymeric ET stent can be reliably positioned without generating a patulous ET. It seems to support ET function for about 3 months before functionality is lost.

Two randomized controlled trials demonstrated no clinical benefit of hydroxychloroquine (HCQ) for either postexposure prophylaxis or early treatment of SARS-CoV-2 infection. Using data from these studies, we calculated the time-weighted average change from baseline SARS-CoV-2 viral load and demonstrated that HCQ did not affect viral clearance.

Cochlear implants are well established devices for treating severe hearing loss. However, due to the trauma caused by the insertion of the electrode and the subsequent formation of connective tissue, their clinical effectiveness varies. The aim of the current study was to achieve a long-term reduction in connective tissue growth and impedance by combining surface patterns on the electrode array with a poly-L-lactide coating containing 20% diclofenac. Three groups of six guinea pigs each (control, structure, structure with diclofenac in the coating) were implanted for four weeks. The hearing thresholds were measured before implantation and after 28 days, and impedances were monitored over time. After histological preparation, connective tissue growth and spiral ganglion neuron (SGN) survival were quantified. The hearing thresholds and impedances increased over time in all groups, showing no significant differences. The treatment groups showed increased damage in the cochlea, which appeared to be caused by the elevated parts of the microstructures. This seems to be amplified by the trauma model used in the current study. The impedances correlated with connective tissue growth near the electrode contacts. In addition, SGN survival was negatively correlated with the presence of connective tissue, both of which highlight the importance of successfully reducing connective tissue formation after cochlear implantation.

Background: Using antibiotics without medical guidance (non-prescription use) is a potential safety threat to individual and public health. Patients' situations can impact their intentions to use non-prescription antibiotics in the future (intended use). This survey (1) explores the dimensionality of 13 predefined situations to identify ‘summary factor,’ which include conceptually similar situations that influence patients’ intended use of non-prescription antibiotics, and (2) identifies the sociodemographic predictors associated with these summary factors. Methods: A cross-sectional survey was conducted from January 2020–June 2021 in the waiting rooms of six safety-net primary care clinics and two private emergency departments. We used principal component analysis as a data reduction technique and confirmed the factor structure of the situations (identifying three situational summary factors). Multivariate linear regression identified the sociodemographic predictors (e.g., age, gender, race, education, insurance, healthcare system, language preference, birth country, and health literacy) associated with each summary factor. Results: Of the 564 patients surveyed, the majority were female (72%), Hispanic or Latinx (47%), college-educated (44%), and received public health insurance (e.g., Medicaid or County Financial Assistance) (56%). The largest proportion of patients endorsed intended non-prescription antibiotic use for situations involving high doctor visit costs (29.8%), having leftover prescription antibiotics (50.4%), and experiencing symptom relief with prior use of antibiotics (47.5%) (Figure 1). We identified three situational summary factors: (1) perceived barriers to a doctor visit and receiving a prescription (Cronbach’s alpha [α]=0.96), (2) convenience and accessibility of non-prescription antibiotics (α=0.81), and (3) previous symptom relief with antibiotics (α=0.95). After controlling for gender, race, education, insurance, language preference, birth country, and health literacy, our multivariate regression results revealed that younger patients (P < 0 .04) and patients attending the safety-net health system (P < 0 .001) had more intended use of non-prescription antibiotics for all three summary factors (Figure 2). Conclusions: Our study revealed that younger patients and individuals receiving care from the safety-net clinics had an increased risk of intended non-prescription antibiotic use across all summary factors. Future stewardship interventions should consider the types of situations that drive patients' decisions to use antibiotics without a prescription. Interventions aimed at reducing barriers to healthcare (e.g., high costs and long waits associated with doctor appointments) and educating individuals on the risks associated with inappropriate antibiotic use while providing alternative (non-antibiotic) treatment options may reduce antibiotic use and antimicrobial resistance. Acknowledgments: This work is supported by grant number R01HS026901 from AHRQ and NRSA T-32 (6T32HC10031).

Coronavirus disease 2019 symptom definitions rarely include symptom severity. We collected daily nasal swab samples and symptom diaries from contacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case patients. Requiring ≥1 moderate or severe symptom reduced sensitivity to predict SARS-CoV-2 shedding from 60.0% (95% confidence interval [CI], 52.9%-66.7%) to 31.5% (95% CI, 25.7%- 38.0%) but increased specificity from 77.5% (95% CI, 75.3%-79.5%) to 93.8% (95% CI, 92.7%-94.8%).

Unmet needs in the treatment of chronic otitis media and Eustachian tube dysfunction (ETD) triggered the development of stents for the Eustachian tube (ET). In this study, for the first time, stents were placed in an artificially blocked ET to evaluate stent function. Eight adult female sheep were injected with stabilized hyaluronic acid (HA) on both sides to induce ETD. Subsequently, a tapered nitinol ET stent was inserted on one side, and animals were examined bilaterally by endoscopy, tympanometry, cone beam computed tomography, and final histology. Seven of the stents were placed in the desired cartilaginous portion of the ET. At the end of the study, one stented side appeared slightly open; all other ET orifices were closed. Tympanometry revealed re-ventilation of the middle ear in four out of seven correctly stented animals within 3 to 6 weeks after stent insertion. The major amount of HA was found at the pharyngeal orifice of the ET anterior to the stent. Thus, the stent position did not completely align with the HA position. While a functional analysis will require refinement of the experimental setup, this study provides first promising results for stent insertion in a sheep model of ETD.

Abstract Background Circulating extracellular vesicles (EVs) are increased in preeclampsia (PE) and are associated with severity and progression. We examined in this exploratory cohort study if the mRNAs and long noncoding RNAs (lncRNAs) in plasma-derived EVs were dysregulated in PE compared to normal pregnancy and display different temporal patterns during gestation. Methods We isolated EVs from plasma at weeks 22–24 and 36–38 in women with and without PE (n=7 in each group) and performed RNA-seq, focusing on mRNAs and lncRNAs. We validated highly expressed mitochondrial and platelet-derived RNAs discovered from central pathways in 60 women with/without PE. We examined further one of the regulated RNAs, noncoding mitochondrially encoded tRNA alanine (MT-TA), in leukocytes and plasma to investigate its biomarker potential and association with clinical markers of PE. Results We found abundant levels of platelet-derived and mitochondrial RNAs in EVs. Expression of these RNAs were decreased and lncRNAs increased in EVs from PE compared to without PE. These findings were further validated by qPCR for mitochondrial RNAs MT-TA, MT-ND2, MT-CYB and platelet-derived RNAs PPBP, PF4, CLU in EVs. Decreased expression of mitochondrial tRNA MT-TA in leukocytes at 22–24 weeks was strongly associated with the subsequent development of PE. Conclusions Platelet-derived and mitochondrial RNA were highly expressed in plasma EVs and were decreased in EVs isolated from women with PE compared to without PE. LncRNAs were mostly increased in PE. The MT-TA in leukocytes may be a useful biomarker for prediction and/or early detection of PE. Graphical Abstract

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to a global pandemic of coronavirus disease 2019 (COVID-19). Early in the pandemic, efforts were made to test the SARS-CoV-2 antiviral efficacy of repurposed medications that were already approved and available for other indications, including hydroxychloroquine (HCQ) and azithromycin (AZI). To reduce the risk of SARS-CoV-2 exposure for clinical-trial study participants and to conform with lockdowns and social distancing guidelines, biospecimen collection for HCQ and AZI included at-home dried blood spot (DBS) collection rather than standard venipuncture by trained clinicians. In this study, we developed and validated the first sensitive and selective simultaneous LC–MS/MS method to accurately quantitate the concentration of HCQ, HCQ metabolites (Desethylchloroquine [DCQ], Bisdesethylchloroquine [BDCQ], Monodesethylhydroxychloroquine [DHCQ]) and AZI extracted from DBS. The validated method was successfully applied for the quantification of over 2000 DBS specimens to evaluate the pharmacokinetic profile of AZI, HQC, and its metabolites. This new method has a small sample volume requirement (~ 10 µL), results in high sensitivity (1 ng/mL), and would facilitate remotely conducted therapeutic drug monitoring.

BackgroundElectrocardiographic (ECG) features of left bundle branch (LBB) block (LBBB) can be observed in up to 20%–30% of patients suffering from heart failure with reduced ejection fraction. However, predicting which LBBB patients will benefit from cardiac resynchronization therapy (CRT) or conduction system pacing remains challenging. This study aimed to establish a translational model of LBBB to enhance our understanding of its pathophysiology and improve therapeutic approaches.MethodsFourteen male pigs underwent radiofrequency catheter ablation of the proximal LBB under fluoroscopy and ECG guidance. Comprehensive clinical assessments (12-lead ECG, bloodsampling, echocardiography, electroanatomical mapping) were conducted before LBBB induction, after 7, and 21 days. Three pigs received CRT pacemakers 7 days after LBB ablation to assess resynchronization feasibility.ResultsFollowing proximal LBB ablation, ECGs displayed characteristic LBBB features, including QRS widening, slurring in left lateral leads, and QRS axis changes. QRS duration increased from 64.2 ± 4.2 ms to 86.6 ± 12.1 ms, and R wave peak time in V6 extended from 21.3 ± 3.6 ms to 45.7 ± 12.6 ms. Echocardiography confirmed cardiac electromechanical dyssynchrony, with septal flash appearance, prolonged septal-to-posterior-wall motion delay, and extended ventricular electromechanical delays. Electroanatomical mapping revealed a left ventricular breakthrough site shift and significantly prolonged left ventricular activation times. RF-induced LBBB persisted for 3 weeks. CRT reduced QRS duration to 75.9 ± 8.6 ms, demonstrating successful resynchronization.ConclusionThis porcine model accurately replicates the electrical and electromechanical characteristics of LBBB observed in patients. It provides a practical, cost-effective, and reproducible platform to investigate molecular and translational aspects of cardiac electromechanical dyssynchrony in a controlled and clinically relevant setting.

Abstract Hydroxychloroquine (HCQ) is Food and Drug Administration (FDA)‐approved for malaria, systemic and chronic discoid lupus erythematosus, and rheumatoid arthritis. Because HCQ has a proposed multimodal mechanism of action and a well‐established safety profile, it is often investigated as a repurposed therapeutic for a range of indications. There is a large degree of uncertainty in HCQ pharmacokinetic (PK) parameters which complicates dose selection when investigating its use in new disease states. Complications with HCQ dose selection emerged as multiple clinical trials investigated HCQ as a potential therapeutic in the early stages of the COVID‐19 pandemic. In addition to uncertainty in baseline HCQ PK parameters, it was not clear if disease‐related consequences of SARS‐CoV‐2 infection/COVID‐19 would be expected to impact the PK of HCQ and its primary metabolite desethylhydroxychloroquine (DHCQ). To address the question whether SARS‐CoV‐2 infection/COVID‐19 impacted HCQ and DHCQ PK, dried blood spot samples were collected from SARS‐CoV‐2(−)/(+) participants administered HCQ. When a previously published physiologically based pharmacokinetic (PBPK) model was used to fit the data, the variability in exposure of HCQ and DHCQ was not adequately captured and DHCQ concentrations were overestimated. Improvements to the previous PBPK model were made by incorporating the known range of blood to plasma concentration ratios (B/P) for each compound, adjusting HCQ and DHCQ distribution settings, and optimizing DHCQ clearance. The final PBPK model adequately captured the HCQ and DHCQ concentrations observed in SARS‐CoV‐2(−)/(+)participants, and incorporating COVID‐19‐associated changes in cytochrome P450 activity did not further improve model performance for the SARS‐CoV‐2(+) population.

BackgroundEffective prevention against coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently limited to nonpharmaceutical strategies. Laboratory and observational data suggested that hydroxychloroquine had biological activity against SARS-CoV-2, potentially permitting its use for prevention.ObjectiveTo test hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.DesignHousehold-randomized, double-blind, controlled trial of hydroxychloroquine postexposure prophylaxis. (ClinicalTrials.gov: NCT04328961).SettingNational U.S. multicenter study.ParticipantsClose contacts recently exposed ( 0.20). The frequency of participants experiencing adverse events was higher in the hydroxychloroquine group than the control group (66 [16.2%] versus 46 [10.9%], respectively; P = 0.026).LimitationThe delay between exposure, and then baseline testing and the first dose of hydroxychloroquine or ascorbic acid, was a median of 2 days.ConclusionThis rigorous randomized controlled trial among persons with recent exposure excluded a clinically meaningful effect of hydroxychloroquine as postexposure prophylaxis to prevent SARS-CoV-2 infection.Primary funding sourceBill & Melinda Gates Foundation.

Positional plagiocephaly is a deformational cranial flattening frequently treated in pediatric neurosurgical practice. Positional maneuvers and orthotic helmet therapy are preferred therapeutic options for moderate-to-severe forms. Treatment response seems to be age-dependent. Nevertheless, predictive data are vague, and cost-efficiency might be a limiting factor for treatment. The purpose of this study was to investigate the early predictive value of sonographic parameters on the efficacy of orthotic helmet therapy through the assessment of changes in skull shape and correlation of the parameters with caliper cephalometry values and with age. A consecutive cohort of 49 patients < 10 months of age, undergoing orthotic helmet therapy for positional plagiocephaly, was recruited prospectively. The authors routinely assessed the patency of the lambdoid sutures by ultrasound and the following additional skull parameters were measured: suture width, adjacent full bone thickness, adjacent cortical bone thickness and occipital angle. Caliper cephalometric values, as well as demographic and clinical data were collected. Retrospective data analysis showed an inverse relation between both cortical and full skull bone thickness and early treatment efficacy, defined by a reduction in the occipital angle. The improvement of sonographic parameters correlated with the development of cranial caliper cephalometry values. In conclusion, the sonographic assessment of skull bone thickness is a safe and cost-effective tool to predict the early efficacy of orthotic helmet therapy in positional plagiocephaly and might, therefore, help the clinician to foresee the potential evolution of the deformity.

The Eustachian tube (ET) is a bottleneck when it comes to middle ear (ME) health. If its function is impaired, this can lead to serious consequences for the patient, such as hearing problems or deafness. Therefore, this study investigated a tapered nitinol stent (3–5 mm × 14 mm) for the human ET as a potential new permanent treatment for chronic Eustachian tube dysfunction (ETD) and thus ME ventilation disorders. The self-expanding stent was inserted unilaterally into the ET of 24 sheep with observation periods of 3, 6, and 12 months. Local tissue effects and the safety of the stent insertion were analyzed based on regular endoscopic checks, weekly tympanometry measurements, final imaging, and histological examinations. The animals showed no stent-related health restrictions. However, the individual anatomy and stenting procedure had an influence on the results. The tissue reaction in the endoscopic examinations was mild even though no concomitant antibiotics were administered. After all three monitoring periods, stented ETs had a significantly larger ET lumen than the non-stented contralateral ETs. However, tissue growth was detected in the stent. Overall, the first long-term study on an ET stent showed that the tapered ET stent could be a promising treatment option for ETD.

Background The extent to which sex, racial, and ethnic groups receive advanced heart therapies equitably is unclear. We estimated the population rate of left ventricular assist device (LVAD) and heart transplant (HT) use among (non‐Hispanic) White, Hispanic, and (non‐Hispanic) Black men and women who have heart failure with reduced ejection fraction (HFrEF). Methods and Results We used a retrospective cohort design combining counts of LVAD and HT procedures from 19 state inpatient discharge databases from 2010 to 2018 with counts of adults with HFrEF. Our primary outcome measures were the number of LVAD and HT procedures per 1000 adults with HFrEF. The main exposures were sex, race, ethnicity, and age. We used Poisson regression models to estimate procedure rates adjusted for differences in age, sex, race, and ethnicity. In 2018, the estimated population of adults aged 35 to 84 years with HFrEF was 69 736, of whom 44% were women. Among men, the LVAD rate was 45.6, and the HT rate was 26.9. Relative to men, LVAD and HT rates were 72% and 62% lower among women (P0.05) or higher (P