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OBJECTIVES: The COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use. METHODS: Cross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use. RESULTS: We received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not. CONCLUSIONS: Early in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.

The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions. Multi-group confirmatory factor analysis indicated that configural and metric invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional SWLS model has universal applicability. Full scalar invariance was achieved across gender identities and age groups. Based on alignment optimisation methods, partial scalar invariance was achieved across all but three national groups and across all languages represented in the BINS. There were large differences in latent SWLS means across nations and languages, but negligible-to-small differences across gender identities and age groups. Across nations, greater life satisfaction was significantly associated with greater financial security and being in a committed relationship or married. The results of this study suggest that the SWLS largely assesses a common unidimensional construct of life satisfaction irrespective of respondent characteristics (i.e., national group, gender identities, and age group) or survey presentation (i.e., survey language). This has important implications for the assessment of life satisfaction across nations and provides information that will be useful for practitioners aiming to promote subjective well-being internationally.

ObjectivesEmergency department (ED) health care personnel (HCP) are at risk of exposure to SARS-CoV-2. The objective of this study was to determine the attributable risk of SARS-CoV-2 infection from providing ED care, describe personal protective equipment use, and identify modifiable ED risk factors. We hypothesized that providing ED patient care increases the probability of acquiring SARS-CoV-2 infection.MethodsWe conducted a multicenter prospective cohort study of 1,673 ED physicians, advanced practice providers (APPs), nurses, and nonclinical staff at 20 U.S. centers over 20 weeks (May to December 2020; before vaccine availability) to detect a four-percentage point increased SARS-CoV-2 incidence among HCP related to direct patient care. Participants provided monthly nasal and serology specimens and weekly exposure and procedure information. We used multivariable regression and recursive partitioning to identify risk factors.ResultsOver 29,825 person-weeks, 75 participants (4.5%) acquired SARS-CoV-2 infection (31 were asymptomatic). Physicians/APPs (aOR 1.07; 95% CI 0.56-2.03) did not have higher risk of becoming infected compared to nonclinical staff, but nurses had a marginally increased risk (aOR 1.91; 95% CI 0.99-3.68). Over 99% of participants used CDC-recommended personal protective equipment (PPE), but PPE lapses occurred in 22.1% of person-weeks and 32.1% of SARS-CoV-2-infected patient intubations. The following factors were associated with infection: household SARS-CoV-2 exposure; hospital and community SARS-CoV-2 burden; community exposure; and mask non-use in public. SARS-CoV-2 intubation was not associated with infection (attributable risk fraction 13.8%; 95% CI -2.0-38.2%), and nor were PPE lapses.ConclusionsAmong unvaccinated U.S. ED HCP during the height of the pandemic, the risk of SARS-CoV-2 infection was similar in nonclinical staff and HCP engaged in direct patient care. Many identified risk factors were related to community exposures.

RationaleDespite national guidelines with recommendations on induction of labor (IOL), large variation in the use of this intervention exists between regions in the Netherlands. Guidelines are translated into protocols, which give a contextual description of medical practice provided in a given region. Possibly, protocols developed by regional multidisciplinary maternity care networks (MCNs) contribute to the regional variation in IOL.Aims and objectivesThe aim of this study was to assess the variation between regional protocols and national guidelines regarding recommendations on IOL and the extent to which this contributes to practice variation.MethodWe performed a systematic document analysis using the Ready materials, Extract data, Analyze, Distil (READ) approach. National guidelines (n = 4) and regional protocols (n = 18) from six MCNs on topics linked to IOL were assessed between October 2021 and April 2022. An analytical framework was used to extract data for the comparison of regional protocols.ResultsSome MCNs followed all the recommendations of national guidelines in their regional protocols, others developed their own recommendations, and for some this varied per topic. When developing their own recommendations, MCNs with a high percentage of IOL added additional risk factors and stricter cut-off values. In contrast, MCNs with a low percentage of IOL added more care options for continuing midwife-led care. No clear relationship was observed between the Appraisal of Guidelines for Research & Evaluation (AGREE) scores of the national guidelines and the extent to which regional protocols complied with the recommendations.ConclusionThe translation of national guidelines to regional protocols seemed arbitrary and not very systematic. To reduce unwarranted practice variation in the use of IOL, guidance is needed to better align regional protocols with national guidelines, while including appropriate contextual factors and allowing women's preferences. Additionally, healthcare providers should be trained in practicing evidence-based medicine instead of using evidence.

ObjectivesThe COVID-19 pandemic placed health care personnel (HCP) at risk for stress, anxiety, burnout, and post-traumatic stress disorder (PTSD). To address this, hospitals developed programs to mitigate risk. The objectives of the current study were to measure the availability and use of these programs in a cohort of academic emergency departments (EDs) in the United States early in the pandemic and identify factors associated with program use.MethodsCross-sectional survey of ED HCP in 21 academic EDs in 15 states between June and September 2020. Site investigators provided data on the availability of 28 programs grouped into 9 categories. Individual support programs included: financial, workload mitigation, individual COVID-19 testing, emotional (e.g., mental health hotline), and instrumental (e.g., childcare) Clinical work support programs included: COVID-19 team communication (e.g., debriefing critical incident), patient-family communication facilitation, patient services (e.g., social work, ethics consultation), and system-level exposure reduction. Participants provided corresponding data on whether they used the programs. We used generalized linear mixed models clustered on site to measure the association between demographic and facility characteristics and program use.ResultsWe received 1,541 survey responses (96% response rate) from emergency physicians or advanced practice providers, nurses, and nonclinical staff. Program availability in each of the 9 categories was high (>95% of hospitals). Program use was variable, with clinical work support programs used more frequently (28-50% of eligible HCP across categories) than individual employee support programs (6-13% of eligible HCP across categories). Fifty-seven percent of respondents reported that the COVID-19 pandemic had affected their stress and anxiety, and 12% were at elevated risk for PTSD. Program use did not significantly differ for HCP who reported symptoms of anxiety and/or stress compared to those who did not.ConclusionsEarly in the pandemic, support programs were widely available to ED HCP, but program use was low. Future work will focus on identifying barriers and facilitators to use and specific programs most likely to be effective during periods of highest occupational stress.

ObjectiveNegative affect variability is associated with increased symptoms of internalizing psychopathology (i.e., depression, anxiety). The Contrast Avoidance Model (CAM) suggests that individuals with anxiety avoid negative emotional shifts by maintaining pathological worry. Recent evidence also suggests that the CAM can be applied to major depression and social phobia, both characterized by negative affect changes. Here, we compare negative affect variability between individuals with a variety of anxiety and depression diagnoses by measuring the levels and degree of change in the sentiment of their online communications.MethodParticipants were 1,853 individuals on Twitter who reported that they had been clinically diagnosed with an anxiety disorder (A cohort, n = 896) or a depressive disorder (D cohort, n = 957). Mean negative affect (NA) and negative affect variability were calculated using the Valence Aware Dictionary for Sentiment Reasoning (VADER), an accurate sentiment analysis tool that scores text in terms of its negative affect content.ResultsFindings showed differences in negative affect variability between the D and A cohort, with higher levels of NA variability in the D cohort than the A cohort, U = 367210, p < .001, r = 0.14, d = 0.25. Furthermore, we found that A and D cohorts had different average NA, with the D cohort showing higher NA overall, U = 377368, p < .001, r = 0.12, d = 0.21.LimitationsOur sample is limited to individuals who disclosed their diagnoses online, which may involve bias due to self-selection and stigma. Our sentiment analysis of online text may not completely capture all nuances of individual affect.ConclusionsIndividuals with depression diagnoses showed a higher degree of negative affect variability compared to individuals with anxiety disorders. Our findings support the idea that negative affect variability can be measured using computational approaches on large-scale social media data and that social media data can be used to study naturally occurring mental health effects at scale.

Preventive chemotherapy by mass drug administration is globally recommended as the primary method of reaching the elimination of schistosomiasis, especially in the high risk-paediatric population. This systematic review provides a summary of the effects of paediatric schistosomiasis control programs on eliminating schistosomiasis in sub-Saharan Africa. A systematic search was conducted in PubMed, EBSCOhost, and other databases to obtain studies regarding the effects of paediatric schistosomiasis control programmes in sub-Saharan Africa. 3455 studies were screened for eligibility, included articles reported on both paediatrics control programmes and schistosomiasis, and articles were excluded when they did not report on schistosomiasis control programmes in paediatrics exclusively. 40 selected studies were critically appraised using the JBI critical appraisal tools for relevance and 30 studies were included in the study. An in-depth quantitative descriptive analysis was conducted, and a comprehensive narrative summary explained the results within the scope of the review questions. The results show that despite preventive chemotherapy lowering schistosomiasis prevalence, chances of re-infection are high in endemic areas. Preventive chemotherapy without complementary interventions including safe water provision and proper sanitation, snail control and health education on the aetiology of schistosomiasis, transmission pattern and control practices might not eliminate schistosomiasis.

[This corrects the article DOI: 10.1371/journal.pone.0278550.].

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation.

Background Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD). Methods This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality. Results In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65–0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4–45.3) and was 26.6 (13.0–63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups. Conclusions Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. Trial registration ClinicalTrials.gov, NCT04762524. Registered 02/21/21—Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1.

IntroductionConsensus group methods such as the Nominal Group Technique (NGT) and Delphi method are commonly used in research to elicit and synthesize expert opinions when evidence is lacking. Traditionally, the NGT involves a face-to-face interaction. However, due to the COVID-19 pandemic, many in-person meetings have moved to online settings. It is unclear to what extent the NGT has been undertaken in virtual settings. The overarching aim of this scoping review is to explore the use of the virtual NGT in research. Our specific objectives are to answer the following questions: To what extent has the NGT been used virtually? What modifications were made to accommodate this online format? What advantages and disadvantages were noted by authors in comparison with the face-to-face mode of the technique?Materials and methodsThis scoping review will follow the steps outlined by Arksey and O'Malley and the PRISMA-ScR guidelines. Several pilot searches were completed to refine inclusion and exclusion criteria. Media Synchronicity Theory will provide a conceptual framework to inform the research, including data extraction and summarizing results. As an additional extension to the literature review, online interviews with corresponding authors will be conducted to gather further information.

Background Diagnosing concomitant pulmonary embolism (PE) in COVID-19 patients remains challenging. As such, PE may be overlooked. We compared the diagnostic yield of systematic PE-screening based on the YEARS-algorithm to PE-screening based on clinical gestalt in emergency department (ED) patients with COVID-19. Methods We included all ED patients who were admitted because of COVID-19 between March 2020 and February 2021. Patients already receiving anticoagulant treatment were excluded. Up to April 7, 2020, the decision to perform CT-pulmonary angiography (CTPA) was based on physician’s clinical gestalt (clinical gestalt cohort). From April 7 onwards, systematic PE-screening was performed by CTPA if D-dimer level was ≥1000 ug/L, or ≥500 ug/L in case of ≥1 YEARS-item (systematic screening cohort). Results 1095 ED patients with COVID-19 were admitted. After applying exclusion criteria, 289 were included in the clinical gestalt and 574 in the systematic screening cohort. The number of PE diagnoses was significantly higher in the systematic screening cohort compared to the clinical gestalt cohort: 8.2% vs. 1.0% (3/289 vs. 47/574; p100 mg/L (OR 2.78, 95%CI 1.37–5.66, p = 0.005) were independently associated with PE. Conclusion In ED patients with COVID-19, the number of PE diagnosis was significantly higher in the cohort that underwent systematic PE screening based on the YEARS-algorithm in comparison with the clinical gestalt cohort, with a number needed to test of 7.1 CTPAs to detect one PE.

Galleria mellonella larvae have been increasingly used in research, including microbial infection studies. They act as suitable preliminary infection models to study host-pathogen interactions due to their advantages, such as the ability to survive at 37°C mimicking human body temperature, their immune system shares similarities with mammalian immune systems, and their short life cycle allowing large-scale studies. Here, we present a protocol for simple rearing and maintenance of G. mellonella without requiring special instruments and specialized training. This allows the continuous supply of healthy G. mellonella for research purposes. Besides, this protocol also provides detailed procedures on the (i) G. mellonella infection assays (killing assay and bacterial burden assay) for virulence studies and (ii) bacterial cell harvesting from infected larvae and RNA extraction for bacterial gene expression studies during infection. Our protocol could not only be used in the studies of A. baumannii virulence but can also be modified according to different bacterial strains.

Background Practice variation in healthcare is a complex issue. We focused on practice variation in induction of labor between maternity care networks in the Netherlands. These collaborations of hospitals and midwifery practices are jointly responsible for providing high-quality maternity care. We explored the association between induction rates and maternal and perinatal outcomes. Methods In a retrospective population-based cohort study, we included records of 184,422 women who had a singleton, vertex birth of their first child after a gestation of at least 37 weeks in the years 2016–2018. We calculated induction rates for each maternity care network. We divided networks in induction rate categories: lowest (Q1), moderate (Q2-3) and highest quartile (Q4). We explored the association of these categories with unplanned caesarean sections, unfavorable maternal outcomes and adverse perinatal outcomes using descriptive statistics and multilevel logistic regression analysis corrected for population characteristics. Findings The induction rate ranged from 14.3% to 41.1% (mean 24.4%, SD 5.3). Women in Q1 had fewer unplanned caesarean sections (Q1: 10.2%, Q2-3: 12.1%; Q4: 12.8%), less unfavorable maternal outcomes (Q1: 33.8%; Q2-3: 35.7%; Q4: 36.3%) and less adverse perinatal outcomes (Q1: 1.0%; Q2-3: 1.1%; Q4: 1.3%). The multilevel analysis showed a lower unplanned caesarean section rate in Q1 in comparison with reference category Q2-3 (OR 0.83; p = .009). The unplanned caesarean section rate in Q4 was similar to the reference category. No significant associations with unfavorable maternal or adverse perinatal outcomes were observed. Conclusion Practice variation in labor induction is high in Dutch maternity care networks, with limited association with maternal outcomes and no association with perinatal outcomes. Networks with low induction rates had lower unplanned caesarean section rates compared to networks with moderate rates. Further in-depth research is necessary to understand the mechanisms that contribute to practice variation and the observed association with unplanned caesarean sections.

BackgroundAlthough compression therapy is well established for patients with deep venous thrombosis (DVT) and chronic venous disease (CVD), considerable variation exists in its organization in clinical practice which may impact patient outcomes. The current study aims to deepen our understanding of the main drivers of the complex care organization for compression therapy and to identify targets for improvement.MethodsThis realist evaluation includes a mixed-method design consisting of semi-structured interviews with patients and health care professionals involved in compression therapy (n = 30), stakeholder meetings (n = 2) and surveys (n = 114). Data were collected to create the content of context-mechanism-outcome-configurations (CMOcs) important in compression therapy. Based on these CMOcs, targets for improvement to optimize the organization of compression care were identified.ResultsWe identified overarching context factors and mechanisms targeting four optimal outcomes for the organization of compression therapy: selecting initial compression therapy types that support patient's self-reliance (1), evidence based selection of elastic compression stocking type and class (2), patient-based selection of assistive devices (3), individualizing treatment duration for DVT patients (4a) and providing follow-up for CVD patients (4b). We found that increasing health care professionals' knowledge of compression therapy, the availability of unambiguous protocols and guidelines, increasing patient involvement (and if applicable their informal care giver) in the decision making process, the accessible availability of resources, and increasing interdisciplinary consultation enhanced desirable outcomes. These targets triggered mechanisms such as increased health care professionals' willingness, confidence and motivation to provide patient-based care and increased patients' self-confidence and self-efficacy.ConclusionsThis study provides a detailed insight into what needs to be in place to optimize compression care and identified five main targets for improvement.

Rationale: Despite national guidelines with recommendations on induction of labor (IOL), large variation in the use of this intervention exists between regions in the Netherlands. Guidelines are translated into protocols, which give a contextual description of medical practice provided in a given region. Possibly, protocols developed by regional multidisciplinary maternity care networks (MCNs) contribute to the regional variation in IOL. Aims and objectives: The aim of this study was to assess the variation between regional protocols and national guidelines regarding recommendations on IOL and the extent to which this contributes to practice variation. Method: We performed a systematic document analysis using the Ready materials, Extract data, Analyze, Distil (READ) approach. National guidelines (n = 4) and regional protocols (n = 18) from six MCNs on topics linked to IOL were assessed between October 2021 and April 2022. An analytical framework was used to extract data for the comparison of regional protocols. Results: Some MCNs followed all the recommendations of national guidelines in their regional protocols, others developed their own recommendations, and for some this varied per topic. When developing their own recommendations, MCNs with a high percentage of IOL added additional risk factors and stricter cut-off values. In contrast, MCNs with a low percentage of IOL added more care options for continuing midwife-led care. No clear relationship was observed between the Appraisal of Guidelines for Research & Evaluation (AGREE) scores of the national guidelines and the extent to which regional protocols complied with the recommendations. Conclusion: The translation of national guidelines to regional protocols seemed arbitrary and not very systematic. To reduce unwarranted practice variation in the use of IOL, guidance is needed to better align regional protocols with national guidelines, while including appropriate contextual factors and allowing women's preferences. Additionally, healthcare providers should be trained in practicing evidence-based medicine instead of using evidence. [ABSTRACT FROM AUTHOR]

Natural disasters can have devastating and long-lasting effects on a community’s emotional well-being. These effects may be distributed unequally, affecting some communities more profoundly and possibly over longer time periods than others. Here, we analyze the effects of four major US hurricanes, namely, Irma, Harvey, Florence, and Dorian on the emotional well-being of the affected communities and regions. We show that a community’s emotional response to a hurricane event can be measured from the content of social media that its population posted before, during, and after the hurricane. For each hurricane making landfall in the US, we observe a significant decrease in sentiment in the affected areas before and during the hurricane followed by a rapid return to pre-hurricane baseline, often within 1-2 weeks. However, some communities exhibit markedly different rates of decline and return to previous equilibrium levels. This points towards the possibility of measuring the emotional resilience of communities from the dynamics of their online emotional response.

The use of Engineered Heart Tissues (EHT) as in vitro model for disease modeling and drug screening has increased, as they provide important insight into the genetic mechanisms, cardiac toxicity or drug responses. Consequently, this has highlighted the need for a standardized, unbiased, robust and automatic way to analyze hallmark physiological features of EHTs. In this study we described and validated a standalone application to analyze physiological features of EHTs in an automatic, robust, and unbiased way, using low computational time. The standalone application "EHT Analysis" contains two analysis modes (automatic and manual) to analyzes the contractile properties and the contraction kinetics of EHTs from high speed bright field videos. As output data, the graphs of displacement, contraction force and contraction kinetics per file will be generated together with the raw data. Additionally, it also generates a summary file containing all the data from the analyzed files, which facilitates and speeds up the post analysis. From our study we highlight the importance of analyzing the axial stress which is the force per surface area (μN/mm2). This allows to have a readout overtime of tissue compaction, axial stress and leave the option to calculate at the end point of an experiment the physiological cross-section area (PSCA). We demonstrated the utility of this tool by analyzing contractile properties and compaction over time of EHTs made out of a double reporter human pluripotent stem cell (hPSC) line (NKX2.5EGFP/+-COUP-TFIImCherry/+) and different ratios of human adult cardiac fibroblasts (HCF). Our standalone application "EHT Analysis" can be applied for different studies where the physiological features of EHTs needs to be analyzed under the effect of a drug compound or in a disease model.

HypothesisTo develop and validate the optimal design and evaluate accuracy of individualized 3D- printed surgical guides for cochlear implantation.BackgroundPositioning and fixation of the cochlear implant (CI) are commonly performed free hand. Applications of 3-dimensional (3D) technology now allow us to make patient specific, bone supported surgical guides, to aid CI surgeons with precise placement and drilling out the bony well which accommodates the receiver/stimulator device of the CI.MethodsCone beam CT (CBCT) scans were acquired from temporal bones in 9 cadaveric heads (18 ears), followed by virtual planning of the CI position. Surgical, bone-supported drilling guides were designed to conduct a minimally invasive procedure and were 3D-printed. Fixation screws were used to keep the guide in place in predetermined bone areas. Specimens were implanted with 3 different CI models. After implantation, CBCT scans of the implanted specimens were performed. Accuracy of CI placement was assessed by comparing the 3D models of the planned and implanted CI's by calculating the translational and rotational deviations.ResultsMedian translational deviations of placement in the X- and Y-axis were within the predetermined clinically relevant deviation range (< 3 mm per axis); median translational deviation in the Z-axis was 3.41 mm. Median rotational deviations of placement for X-, Y- and Z-rotation were 5.50°, 4.58° and 3.71°, respectively.ConclusionThis study resulted in the first 3D-printed, patient- and CI- model specific surgical guide for positioning during cochlear implantation. The next step for the development and evaluation of this surgical guide will be to evaluate the method in clinical practice.

Ticks and tick-borne diseases cause substantial economic losses to the livestock industry in sub-Saharan Africa. Mazao Tickoff is a novel bioacaricide developed for tick control and is based on the entomopathogenic fungus Metarhizium anisopliae sensu lato (s.l.) isolate ICIPE 7. To date, no randomized controlled study has been undertaken to demonstrate the efficacy of this bioacaricide in reducing natural tick infestation on cattle. To this end, this field trial is designed to evaluate the anti-tick efficacy of Mazao Tickoff on cattle in coastal Kenya compared to a standard chemical tick control protocol. In this prospective, multi-center randomized controlled trial, eligible herds will be randomized by the herd size to the intervention arm in a 1:1:1 ratio to either Triatix® (active ingredient: amitraz); Mazao Tickoff (active ingredient: M. anisopliae ICIPE 7); or placebo (excipients of the Mazao Tickoff), with a total enrollment target of 1,077 cattle. Treatments will be dispensed on Day 0 (defined individually as the day each animal receives the first treatment) and thereafter every two weeks until Day 182. Ticks will be counted on every animal in each herd (herds to be included have at least one animal bearing at least one tick on Day 0), and thereafter on bi-weekly intervals until Day 182. The primary efficacy assessments of Mazao Tickoff will be based on the mean percentage reduction in tick counts at each post-treatment follow-up visit compared to the placebo group and the Triatix® arm. Further, the effect of Mazao Tickoff on the prevalence of common cattle pathogens, Anaplasma marginale and Theileria parva, will be determined by assessing incidence and seroprevalence at four different time points. This protocol describes the first rigorous evaluation of the efficacy of Mazao Tickoff and its potential as a viable alternative non-chemical acaricide tool for tick control in Kenya and elsewhere.

BackgroundMany cardiocirculatory mechanisms are involved in the adaptation to orthostatic stress. While these mechanisms may be impaired in Fontan patients. However, it is yet unclear how Fontan patients, who exhibit a critical fluid balance, respond to orthostatic stress. Angiotensin converting enzyme inhibitors are often prescribed to Fontan patients, but they may negatively influence orthostatic tolerance. Therefore, we evaluated the response to orthostatic stress in pediatric Fontan patients before and after treatment with enalapril.MethodsThirty-five Fontan patients (aged 14 years) with moderate-good systolic ventricular function without pre-existent enalapril treatment were included. Before and after a three-month enalapril treatment period, the hemodynamic response to head-up tilt test was evaluated by various parameters including cardiac index, blood pressure, cerebral blood flow, aortic stiffness and cardiac autonomous nervous activity. Thirty-four healthy subjects (aged 13 years) served as controls.ResultsFontan patients had a decreased cerebral blood flow and increased aortic stiffness in the supine position compared to controls, while all other factors did not differ. Patients and controls showed a comparable response to head-up tilt test for most parameters. Twenty-seven patients completed the enalapril study with a mean dosage of 0.3±0.1mg/kg/day. Most parameters were unaffected by enalapril, only the percent decrease in cardiac index to tilt was higher after treatment, but the cardiac index during tilt was not lower (3.0L/min/m2 pre-enalapril versus 2.8L/min/m2 after treatment; P = 0.15).ConclusionPediatric Fontan patients adequately respond to orthostasis with maintenance of blood pressure and cerebral blood flow and sufficient autonomic response. Enalapril treatment did not alter the response.Clinical trial informationScientific title: ACE inhibition in Fontan patients: its effect on body fluid regulation (sAFE-study). The Netherlands National Trial Register: Trail NL6415. Registered 2017-07-20. Trial information: https://www.trialregister.nl/trial/6415.

Deer genera around the globe are threatened by anthropogenic interference. The translocation of alien species and their subsequent genetic introgression into indigenous deer populations is particularly harmful to the species of greatest conservation concern. Products derived from deer, including venison and antler velvet, are also at risk of fraudulent labeling. The current molecular markers used to genetically identify deer species were developed from genome sequences and have limited applicability for cross-species amplification. The absence of efficacious diagnostic techniques for identifying deer species has hampered conservation and wildlife crime investigation efforts. Expressed sequence tag-simple sequence repeat (EST-SSR) markers are reliable tools for individual and species identification, especially in terms of cross-species genotyping. We conducted transcriptome sequencing of sambar (Rusa unicolor) antler velvet and acquired 11,190 EST-SSRs from 65,074 newly assembled unigenes. We identified a total of 55 unambiguous amplicons in sambar (n = 45), which were selected as markers to evaluate cross-species genotyping in sika deer (Cervus nippon, n = 30) and red deer (Cervus elaphus, n = 46), resulting in cross-species amplification rates of 94.5% and 89.1%, respectively. Based on polymorphic information content (>0.25) and genotyping fidelity, we selected 16 of these EST-SSRs for species identification. This marker set revealed significant genetic differentiation based on the fixation index and genetic distance values. Principal coordinate analysis and STRUCTURE analysis revealed distinct clusters of species and clearly identified red-sika hybrids. These markers showed applicability across different genera and proved suitable for identification and phylogenetic analyses across deer species.

Arbovirus outbreaks in communities are affected by how vectors, hosts and non-competent species interact. In this study, we investigate how ecological interactions between species and epidemiological processes influence the invasion potential of a vector-borne disease. We use an eco-epidemiological model to explore the basic reproduction number R0 for a range of interaction strengths in key processes, using West Nile virus infection to parameterize the model. We focus our analysis on intra and interspecific competition between vectors and between hosts, as well as competition with non-competent species. We show that such ecological competition has non-linear effects on R0 and can greatly impact invasion risk. The presence of multiple competing vector species results in lower values for R0 while host competition leads to the highest values of risk of disease invasion. These effects can be understood in terms of how the competitive pressures influence the vector-to-host ratio, which has a positive relationship with R0. We also show numerical examples of how vector feeding preferences become more relevant in high competition conditions between hosts. Under certain conditions, non-competent hosts, which can lead to a dilution effect for the pathogen, can have an amplification effect if they compete strongly with the competent hosts, hence facilitating pathogen invasion in the community.

IntroductionAlthough parental support is an important component in programs designed to prevent overweight in children, current programs pay remarkably little attention to the role of parenting. We therefore developed a web-based parenting program entitled "Making a healthy deal with your child". This e-learning program can be incorporated into existing overweight prevention programs. The aim of this study was to determine the effectiveness of this e-learning program.Materials and methodsThe effectiveness was examined in a two-armed cluster randomized controlled trial. The participants were 475 parent-child dyads of children 9-13 years of age in the Netherlands who participated in an existing schoolclass-based overweight prevention program. At the school grade level, parents were randomly assigned to either the intervention or the control condition. Measurements were taken from both parents and children at baseline, and 5 and 12 months after baseline. Primary outcomes included the child's dietary and sedentary behavior, and level of physical activity. Secondary outcomes included general parenting style, specific parenting practices, and parental self-efficacy. Linear mixed effects models and generalized linear mixed effects models were conducted in R.ResultsIntention-to-treat analyses and completers only revealed no significant effects between the intervention and control condition on energy balance-related behaviors of the child and parenting skills after correction for multiple testing. The parents' mean satisfaction with the e-learning program (on a 10-point scale) was 7.0±1.1.ConclusionsAlthough parents were generally satisfied with the parenting program, following this program had no significant beneficial effects regarding the children's energy balance-related behaviors or the parenting skills compared to the control condition. This program may be more beneficial if used by high-risk groups (e.g. parents of children with unhealthy energy balance-related behaviors and/or with overweight) compared to the general population, warranting further study.

Hypothermia (HT) is a standard of care in the management of hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms of HT are not well understood. We found that at the temperature of 32°C, isolated brain mitochondria exhibited significantly greater resistance to an opening of calcium-induced permeability transition pore (mPTP), compared to 37°C. Mitochondrial calcium buffering capacity (mCBC) was linearly and inversely dependent upon temperature (25°C-37°C). Importantly, at 37°C cyclosporine A did not increase mCBC, but significantly increased mCBC at lower temperature. Because mPTP contributes to reperfusion injury, we hypothesized that HT protects brain by improvement of mitochondrial tolerance to mPTP activation. Immediately after HI-insult, isolated brain mitochondria demonstrated very poor mCBC. At 30 minutes of reperfusion, in mice recovered under normothermia (NT) or HT, mCBC significantly improved. However, at four hours of reperfusion, only NT mice exhibited secondary decline of mCBC. HT-mice maintained their recovered mCBC and this was associated with significant neuroprotection. Direct inverted dependence of mCBC upon temperature in vitro and significantly increased mitochondrial resistance to mPTP activation after therapeutic HT ex vivo suggest that hypothermia-driven inhibition of calcium-induced mitochondrial mPTP activation mechanistically contributes to the neuroprotection associated with hypothermia.

Introduction Gap and step-off measurements are generally used in the surgical decision-making process of distal radius fractures. Unfortunately, there is no consensus on treatment choice as these measurements are prone to inter- and intraobserver variability. In this study, we aim to introduce a new 3D fracture quantification method and compare it to conventional fracture analysis. Methods Forty patients with a minimally displaced intra-articular distal radius fracture that was treated nonoperatively between 2008–2015 were included. 2D-CT images were reassessed by three orthopedic trauma surgeons who performed gap and step-off measurements. Subsequently, 3D models were created and a 3D measurement method for fracture displacement was developed. For each fracture, the ‘3D gap area’ (3D surface between all fracture fragments) was determined by three observers. Interobserver agreements were calculated for all measurements, and the intraobserver agreement was calculated for the new 3D measurement. All patients completed two questionnaires in order to link our measurements to functional outcome. Results The interobserver agreement of the 2D measurements was fair (ICC = 0.54) for the gap and poor (ICC = 0.21) for the step-off. The median gap was 2.8 (IQR: 1.9–3.5) mm and step-off was 0.9 (IQR: 0.0–1.6) mm. Interobserver agreement on 3D gap area measurements was excellent (ICC = 0.81), with a median difference between measurements of 6.0 (IQR: 2.0–19.0) mm2, which indicates reliable assessment of 3D fracture displacement. Intraobserver agreement was also excellent (ICC = 0.98), with a median difference of 4.0 (IQR: 1.5–5.5) mm2. No significant differences in clinical outcome were found between the above and below 2mm displacement groups. The score of the DASH was 3.4 (IQR: 0.4–8.8) versus 4.2 (IQR: 0.0–11.6) respectively. Results from the PRWE questionnaire shows a similar result of 3.5 (IQR: 0.0–12.6) versus 5.0 (IQR: 0.0–25.5). Conclusion 3D gap area is a more objective measurement method compared to the conventional gap and step-off measurements to quantify the level of fracture displacement of distal radius fractures. 3D fracture assessment can be used in addition to the currently used classification systems of distal radius fractures.

ObjectivesEmergency department (ED) health care personnel (HCP) are at risk of exposure to SARS-CoV-2. The objective of this study was to determine the attributable risk of SARS-CoV-2 infection from providing ED care, describe personal protective equipment use, and identify modifiable ED risk factors. We hypothesized that providing ED patient care increases the probability of acquiring SARS-CoV-2 infection.MethodsWe conducted a multicenter prospective cohort study of 1,673 ED physicians, advanced practice providers (APPs), nurses, and nonclinical staff at 20 U.S. centers over 20 weeks (May to December 2020; before vaccine availability) to detect a four-percentage point increased SARS-CoV-2 incidence among HCP related to direct patient care. Participants provided monthly nasal and serology specimens and weekly exposure and procedure information. We used multivariable regression and recursive partitioning to identify risk factors.ResultsOver 29,825 person-weeks, 75 participants (4.5%) acquired SARS-CoV-2 infection (31 were asymptomatic). Physicians/APPs (aOR 1.07; 95% CI 0.56-2.03) did not have higher risk of becoming infected compared to nonclinical staff, but nurses had a marginally increased risk (aOR 1.91; 95% CI 0.99-3.68). Over 99% of participants used CDC-recommended personal protective equipment (PPE), but PPE lapses occurred in 22.1% of person-weeks and 32.1% of SARS-CoV-2-infected patient intubations. The following factors were associated with infection: household SARS-CoV-2 exposure; hospital and community SARS-CoV-2 burden; community exposure; and mask non-use in public. SARS-CoV-2 intubation was not associated with infection (attributable risk fraction 13.8%; 95% CI -2.0-38.2%), and nor were PPE lapses.ConclusionsAmong unvaccinated U.S. ED HCP during the height of the pandemic, the risk of SARS-CoV-2 infection was similar in nonclinical staff and HCP engaged in direct patient care. Many identified risk factors were related to community exposures.

IntroductionMore than 70% of new HIV infections in Asia occurred in eight countries in 2020: Cambodia, China, India, Indonesia, Myanmar, Nepal, Thailand, and Vietnam-with a rising incidence among men who have sex with men (MSM). The World Health Organization (WHO) recommends pre-exposure prophylaxis (PrEP) for those at risk of acquiring HIV, yet wide-scale implementation of PrEP, on a daily or event-driven basis, has been limited in Asia.MethodsThe Optima HIV model was applied to examine the impact of scaling-up PrEP over five-years to cover an additional 15% of MSM compared with baseline coverage, a target deemed feasible by regional experts. Based on behavioral survey data, we assume that covering 15% of higher-risk MSM will cover 30% of all sexual acts in this group. Scenarios to compare the impact of generic-brand daily dosing of PrEP with generic event-driven dosing (15 days a month) were modelled from the start of 2022 to the end of 2026. Cost-effectiveness of generic versus branded PrEP was also assessed for China, the only country with an active patent for branded, higher cost PrEP. The impact on new HIV infections among the entire population and cost per HIV-related disability-adjusted life year (DALY) averted were estimated from the beginning of 2022 to the end of 2031 and from 2022 to 2051.ResultsIf PrEP were scaled-up to cover an additional 15% of MSM engaging in higher-risk behavior from the beginning of 2022 to the end of 2026 in the eight Asian countries considered, an additional 100,000 (66,000-130,000) HIV infections (17%) and 300,000 (198,000-390,000) HIV-related DALYs (3%) could be averted over the 2022 to 2031 period. The estimated cost per HIV-related DALY averted from 2022 to 2031 ranged from US$600 for event-driven generic PrEP in Indonesia to US$34,400 for daily branded PrEP in Thailand. Over a longer timeframe from 2022 to 2051, the cost per HIV-related DALY averted could be reduced to US$100-US$12,700.ConclusionPrEP is a critical tool to further reduce HIV incidence in highly concentrated epidemics. Implementing PrEP in Asia may be cost-effective in settings with increasing HIV prevalence among MSM and if PrEP drug costs can be reduced, PrEP could be more cost-effective over longer timeframes.

Recently, there has been a renewed interest in low-field MRI. Contrast agents (CA) in MRI have magnetic behavior dependent on magnetic field strength. Therefore, the optimal contrast agent for low-field MRI might be different from what is used at higher fields. Ultra-small superparamagnetic iron-oxides (USPIOs), commonly used as negative CA, might also be used for generating positive contrast in low-field MRI. The purpose of this study was to determine whether an USPIO or a gadolinium based contrast agent is more appropriate at low field strengths. Relaxivity values of ferumoxytol (USPIO) and gadoterate (gadolinium based) were used in this research to simulate normalized signal intensity (SI) curves within a concentration range of 0-15 mM. Simulations were experimentally validated on a 0.25T MRI scanner. Simulations and experiments were performed using spin echo (SE), spoiled gradient echo (SGE), and balanced steady-state free precession (bSSFP) sequences. Maximum achievable SIs were assessed for both CAs in a range of concentrations on all sequences. Simulations at 0.25T showed a peak in SIs at low concentrations ferumoxytol versus a wide top at higher concentrations for gadoterate in SE and SGE. Experiments agreed well with the simulations in SE and SGE, but less in the bSSFP sequence due to overestimated relaxivities in simulations. At low magnetic field strengths, ferumoxytol generates similar signal enhancement at lower concentrations than gadoterate.

BackgroundHypertension (HPT) is an essential public health problem affecting both lower and middle-income countries disproportionately. Evidence suggests that HPT is the leading risk factor for cardiovascular diseases and chronic kidney disease. Yet, challenges faced by patients with HPT in Ghana are not sufficiently explored. This study, documents the challenges patients with HPT face in Ghana.MethodsWe used an explorative descriptive qualitative design. Face-to-face in-depth interviews were conducted with 15 patients with HPT. Interviews were recorded and transcribed verbatim. A thematic content analysis procedure was followed to analyse the data.ResultsFour main themes emerged from interviews; three of which pertained to dimensions of challenges and a fourth which pertained to coping strategies. These include: [1] impairment in physical activities and mobility constraints [2]. Psychological challenges such as suicidal ideations, sadness, fear, anxiety, and reduced sexual affection [3]. Socio-economic challenges identified include loss of friends and social network, difficulty in job demands, and financial burden, and [4] coping strategies such as health system support, social support, and religiosity were identified.ConclusionPatients with HPT experience an array of challenges. We suggest that health care facilities incorporate post HPT diagnosis counseling sessions for HPT patients in the study area. Also, the National Health Insurance Authority (NHIA) should re-examine their scope of services; thus, drugs, laboratory services, and electrocardiogram services to avoid the issue of co-payment. Collaboration between healthcare professionals and family relations of patients with HPT ought to also be strengthened to ensure optimal care.

[This corrects the article DOI: 10.1371/journal.pone.0242926.].

BackgroundPrimary spontaneous pneumothorax (PSP) prevalence is typically higher in juvenile patients than in adults. We aimed to evaluate the optimal treatment for primary spontaneous pneumothorax and its efficacy and safety in juveniles.Materials and methodsWe searched PubMed, Embase, and Cochrane databases for eligible studies published from database inception to October 10, 2020, and conducted a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary and secondary outcomes were recurrence rate and hospital stay length, respectively. Odds ratios (OR) and mean differences were used for quantitatively analyzing binary and continuous outcomes, respectively. In total, nine retrospective studies with 1,452 juvenile patients (aged ConclusionsSurgical approach for first-line management might have a greater effect on recurrence prevention than do conservative approaches. An upfront surgery might be an optimal choice for juvenile primary spontaneous pneumothorax.

The evaluation of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) promises valuable information about fundamental brain related mechanisms and may serve as a diagnostic tool for clinical monitoring of therapeutic progress or surgery procedures. However, reports about spontaneous fluctuations of MEP amplitudes causing high intra-individual variability have led to increased concerns about the reliability of this measure. One possible cause for high variability of MEPs could be neuronal oscillatory activity, which reflects fluctuations of membrane potentials that systematically increase and decrease the excitability of neuronal networks. Here, we investigate the dependence of MEP amplitude on oscillation power and phase by combining the application of single pulse TMS over the primary motor cortex with concurrent recordings of electromyography and electroencephalography. Our results show that MEP amplitude is correlated to alpha phase, alpha power as well as beta phase. These findings may help explain corticospinal excitability fluctuations by highlighting the modulatory effect of alpha and beta phase on MEPs. In the future, controlling for such a causal relationship may allow for the development of new protocols, improve this method as a (diagnostic) tool and increase the specificity and efficacy of general TMS applications.

IntroductionPhysical activity (PA) plays an important role in the prevention of cardiovascular diseases, especially in children. Previous studies which investigated the role of PA and sedentary time (ST) in cardiovascular disease used different measurements and found inconsistent results. The current study used recommended standardized measures and provides an overview of PA and ST among Dutch primary school children and their associations with cardiovascular risk factors.Methods503 children (55% girls, mean age (± SD) 10 ± 1y) were included. PA (total PA, lightPA and moderate to vigorous PA (MVPA)) and ST were measured with the Actigraph GT3X accelerometer. PA in different domains was measured with the BAECKE questionnaire. Cardiovascular risk factors included BMI z-score, waist circumference, blood pressure (z-score) and estimated cardiorespiratory fitness (CRF) as measured with the 20 meter shuttle run test.ResultsChildren spent 57 ± 20 min/day (8%) on MVPA and 42% of the children reached the MVPA guideline of 60 min/day. Total PA and MVPA (h/day) were negatively associated with BMI z-score (B = -0.452, p = 0.011) and waist circumference (B = -3.553, p = 0.011) and positively associated with CRF (B = 2.527, p = ConclusionThis study used standardized measures of PA and therefore created an accurate overview of PA, ST and their associations with cardiovascular risk factors. PA and ST were associated with BMI z-score, waist circumference and CRF. The findings emphasize the importance of promoting MVPA in children, but also highlight the potential benefits of reducing ST to improve cardiovascular risk factors.Trial registrationClinicalTrials.gov NCT03440580.

Entrustable professional activities (EPAs), as a focus of learner assessment, are supported by validity evidence. An EPA is a unit of professional practice requiring proficiency in multiple competencies simultaneously, that can be entrusted to a sufficiently competent learner. Taken collectively, a set of EPAs define and inform the curriculum of a specialty training. The goal of this study was to develop a set of EPAs for Dutch PICU fellows. A multistage methodology was employed incorporating sequential input from task force members, a medical education expert, PICU fellowship program directors, and PICU physicians and fellows via a modified three-round Delphi study. In the first modified Delphi round, experts rated indispensability and clarity of preliminary EPAs. In the subsequent rounds, aggregated scores for each EPA and group comments were provided. In round two, respondents rated indispensability and clarity of revised EPAs. Round three was used to gain explicit confirmation of suitability to implement these EPAs. Based on median ratings and content validity index (CVI) analysis for indispensability in the first two rounds, all nine preliminary EPAs covered activities that were deemed essential to the clinical practice of PICU physicians. Based on median ratings and CVI analysis for clarity however, four EPAs needed revision. With an agreement percentage of 93-100% for all individual EPAs as well as the set as a whole, a high degree of consensus among experts was reached in the third round. The resulting nine PICU EPAs provide a succinct overview of the core tasks of Dutch PICU physicians. These EPAs were created as an essential first step towards developing an assessment system for PICU fellows, grounded in core professional activities. The robust methodology used, may have broad applicability for other (sub)specialty training programs aiming to develop specialty specific EPAs.

ObjectiveSeveral epidemiological and clinical reports associate fibromyalgia (FM) with seizure disorders, and clinical studies associate FM diagnosis with psychogenic non-epileptic seizures. However, these associations rely on self-reports of being diagnosed with FM or unstandardized clinical diagnosis in combination with small samples. We investigated the association of FM and self-reported seizures using a large rheumatic disease databank and the current established self-reported, symptom-based FM diagnostic criteria.MethodsWe selected a random observation from 11,378 subjects with rheumatoid arthritis (RA), 2,390 (21.0%) of whom satisfied 2016 revised criteria for FM. Patients were inquired about the presence of any kind of seizures in the previous 6 months, anti-epileptic medications, and patient-reported symptoms and outcomes.ResultsSeizures were reported by 89 RA patients who met FM criteria (FM+) and by 97 patients who did not (FM-), resulting in an age- and sex-adjusted seizure prevalence of 3.74 (95% CI 2.95 to 4.53) per 100 FM+ subjects and 1.08 (95% CI 0.87 to 1.30) in FM- subjects. The seizure odds ratio of FM+ to FM- cases was 3.54 (95% CI 2.65 to 4.74). Seizures were associated to a very similar degree with symptom reporting (somatic symptom count and comorbidity index) as to FM diagnosis variables. RA patients reporting seizures also reported worse pain, quality of life, and functional status. Seizure patients treated with anti-seizure medication had worse outcomes and more comorbidities than seizure patients with no seizure drugs.ConclusionsWe found a significant and similar association of both FM diagnostic variables and FM-related symptom variables, including the number of symptoms and comorbidities, with self-reported seizures in people with RA. The observed association was similar to those found in previous studies of symptoms variables and seizures and does not suggest a unique role for fibromyalgia diagnosis. Rather, it suggests that multi-symptom comorbidity is linked to seizures in a complex and not yet clearly understood way. As the current study relied on self-reported seizures and was not able to distinguish between epileptic and psychogenic nonepileptic seizures, future studies are needed to replicate the findings using both validated FM criteria assessments and clinically verified diagnoses of epileptic and psychogenic seizures.

There is evidence to suggest that people with Complex Regional Pain Syndrome (CRPS) can have altered body representations and spatial cognition. One way of studying these cognitive functions is through manual straight ahead (MSA) pointing, in which participants are required to point straight ahead of their perceived body midline without visual feedback of the hand. We therefore compared endpoint errors from MSA pointing between people with CRPS (n = 17) and matched controls (n = 18), and examined the effect of the arm used (Side of Body; affected/non-dominant, non-affected/dominant). For all participants, pointing errors were biased towards the hand being used. We found moderate evidence of no difference between Groups on endpoint errors, and moderate evidence of no interaction with Side of Body. The differences in variability between Groups were non-significant/inconclusive. Correlational analyses showed no evidence of a relationship between MSA endpoint errors and clinical parameters (e.g. CRPS severity, duration, pain) or questionnaire measures (e.g. body representation, "neglect-like symptoms", upper limb disability). This study is consistent with earlier findings of no difference between people with CRPS and controls on MSA endpoint errors, and is the first to provide statistical evidence of similar performance of these two groups. Our results do not support a relationship between clinical or self-reported measures (e.g. "neglect-like symptoms") and any directional biases in MSA. Our findings may have implications for understanding neurocognitive changes in CRPS.

AimsPrevious studies have already shown early proximal ingrowth, fast osseous integration, and a stable fit of the uncemented Symax hip stem, with excellent clinical and radiographic performance. Aims were to evaluate cumulative revision rates and reasons for revision of the Symax hip stem using Dutch Arthroplasty Register (LROI) data and to assess possible associations between patient characteristics and revision rate of the Symax hip stem.Patients and methodsAll total hip arthroplasties with the uncemented Symax hip stem registered in the LROI between 2007 and 2017 were included (n = 5,013). Kaplan-Meier survival analysis was performed to assess the cumulative 1, 5 and 7-year revision percentages. Cox proportional hazard regression analysis was performed to assess the association between patient and procedural characteristics, and revision arthroplasty of the stem.ResultsCumulative 1, 5, and 7-year revision rates (with 95% confidence interval (CI)) for revision of any component were 1.5% (CI 1.2%-1.8%), 3.2% (CI 2.7%-3.7%), and 3.8% (CI 3.1%-4.4%) respectively. Cumulative 1, 5, and 7-year stem revision rates of the Symax hip stem were 0.9% (CI 0.6%-1.1%), 1.5% (CI 1.1%-1.9%), and 1.7% (CI 1.3%-2.1%) respectively. Periprosthetic fractures (n = 35) and loosening of the stem (n = 30) were the most common reasons for revision of the stem. Revision of the stem was associated with acute fracture as primary diagnosis (Hazard Ratio (HR) 2.4 (CI 1.3-4.3)), or history of a previous surgery to the affected hip (HR 2.7 (CI 1.4-5.2)).ConclusionThis population-based registry study shows revision rates for the Symax hip stem comparable to those for best performing uncemented total hip arthroplasties in the Netherlands. Primary diagnosis of an acute fracture, and history of previous surgery on the affected hip, were significantly associated risk factors for revision of the Symax hip stem, and we discourage the use of the Symax hip stem in these patients.

ObjectiveTo describe clinical characteristics, disease course and outcomes in a large and well-documented cohort of hospitalized COVID-19 patients in the Netherlands.MethodsWe conducted a multicentre retrospective cohort study in The Netherlands including 952 of 1183 consecutively hospitalized patients that were admitted to participating hospitals between March 2nd, 2020, and May 22nd, 2020. Clinical characteristics and laboratory parameters upon admission and during hospitalization were collected until July 1st.ResultsThe median age was 69 years (IQR 58-77 years) and 605 (63.6%) were male. Cardiovascular disease was present in 558 (58.6%) patients. The median time of onset of symptoms prior to hospitalization was 7 days (IQR 5-10). A non ICU admission policy was applicable in 312 (32.8%) patients and in 165 (56.3%) of the severely ill patients admitted to the ward. At admission and during hospitalization, severely ill patients had higher values of CRP, LDH, ferritin and D-dimer with higher neutrophil counts and lower lymphocyte counts. Overall in-hospital mortality was 25.1% and 183 (19.1%) patients were admitted to ICU, of whom 56 (30.6%) died. Patients aged ≥70 years had high mortality, both at the ward (52.4%) and ICU (47.4%). The median length of ICU stay was 8 days longer in patients aged ≥70 years compared to patients aged ≤60 years.ConclusionHospitalized COVID-19 patients aged ≥70 years had high mortality and longer ICU stay compared to patients aged ≤60 years. These findings in combination with the patient burden of an ICU admission and possible long term complications after discharge should encourage us to further investigate the benefit of ICU admission in elderly and fragile COVID-19-patients.

In contrast to AAV, Simian Virus 40 (rSV40) not inducing neutralizing antibodies (NAbs) allowing re-treatment seems a promising vector for neonatal treatment of inherited liver disorders. Several studies have reported efficacy of rSV40 in animal models for inherited liver diseases. In all studies the ubiquitous endogenous early promoter controlled transgene expression establishing expression in all transduced tissues. Restricting this expression to the target tissues reduces the risk of immune response to the therapeutic gene. In this study a liver specific rSV40 vector was generated by inserting a hepatocyte specific promoter. This increased the specificity of the expression of hUGT1A1 in vitro. However, in vivo the efficacy of rSV40 appeared too low to demonstrate tissue specificity while increasing the vector dose was not possible because of toxicity. In contrast to earlier studies, neutralizing antibodies were induced. Overall, the lack of a platform to produce high titered and pure rSV40 particles and the induction of NAbs, renders it a poor candidate for in vivo gene therapy.

BackgroundTo date, survival data on risk factors for COVID-19 mortality in western Europe is limited, and none of the published survival studies have used a competing risk approach. This study aims to identify risk factors for in-hospital mortality in COVID-19 patients in the Netherlands, considering recovery as a competing risk.MethodsIn this observational multicenter cohort study we included adults with PCR-confirmed SARS-CoV-2 infection that were admitted to one of five hospitals in the Netherlands (March to May 2020). We performed a competing risk survival analysis, presenting cause-specific hazard ratios (HRCS) for the effect of preselected factors on the absolute risk of death and recovery.Results1,006 patients were included (63.9% male; median age 69 years, IQR: 58-77). Patients were hospitalized for a median duration of 6 days (IQR: 3-13); 243 (24.6%) of them died, 689 (69.9%) recovered, and 74 (7.4%) were censored. Patients with higher age (HRCS 1.10, 95% CI 1.08-1.12), immunocompromised state (HRCS 1.46, 95% CI 1.08-1.98), who used anticoagulants or antiplatelet medication (HRCS 1.38, 95% CI 1.01-1.88), with higher modified early warning score (MEWS) (HRCS 1.09, 95% CI 1.01-1.18), and higher blood LDH at time of admission (HRCS 6.68, 95% CI 1.95-22.8) had increased risk of death, whereas fever (HRCS 0.70, 95% CI 0.52-0.95) decreased risk of death. We found no increased mortality risk in male patients, high BMI or diabetes.ConclusionOur competing risk survival analysis confirms specific risk factors for COVID-19 mortality in a the Netherlands, which can be used for prediction research, more intense in-hospital monitoring or prioritizing particular patients for new treatments or vaccination.

BackgroundThe COVID-19 pandemic led to mental health fallout in the US; yet research about mental health and COVID-19 primarily rely on samples that may overlook variance in regional mental health. Indeed, between-city comparisons of mental health decline in the US may provide further insight into how the pandemic is disproportionately affecting at-risk groups.PurposeThis study leverages social media and COVID-19-city infection data to measure the longitudinal (January 22- July 31, 2020) mental health effects of the COVID-19 pandemic in 20 metropolitan areas.MethodsWe used longitudinal VADER sentiment analysis of Twitter timelines (January-July 2020) for cohorts in 20 metropolitan areas to examine mood changes over time. We then conducted simple and multivariate Ordinary Least Squares (OLS) regressions to examine the relationship between COVID-19 infection city data, population, population density, and city demographics on sentiment across those 20 cities.ResultsLongitudinal sentiment tracking showed mood declines over time. The univariate OLS regression highlighted a negative linear relationship between COVID-19 city data and online sentiment (β = -.017). Residing in predominantly white cities had a protective effect against COVID-19 driven negative mood (β = .0629, p < .001).DiscussionOur results reveal that metropolitan areas with larger communities of color experienced a greater subjective well-being decline than predominantly white cities, which we attribute to clinical and socioeconomic correlates that place communities of color at greater risk of COVID-19.ConclusionThe COVID-19 pandemic is a driver of declining US mood in 20 metropolitan cities. Other factors, including social unrest and local demographics, may compound and exacerbate mental health outlook in racially diverse cities.

ObjectivePrisoners constitute a high-risk group for suicide, with suicide rates about 5 to 8 times higher than in the general population. The first weeks of imprisonment are a particularly vulnerable time, but there is limited knowledge about the risk factors for either early or late suicide events.MethodsBased on a national total sample of prison suicides in Germany between 2005 and 2017, suicides within the first 2 (4 and 8) weeks after reception into prison were matched by age and penalty length with cases that occurred later. Factors that potentially influence the timing of suicide were investigated.ResultsThe study has shown that 16.7% (31.5%) of all 390 suicides in German prisons occurred within the first two weeks (two months) of imprisonment. Factors that facilitate adaptation to the prison environment (e.g. prior prison experience) were negatively associated with early suicide events. Factors that hindered the adaptation process (e.g. withdrawal from illicit drugs) were observed more frequently in early suicide events than in late ones. These factors are active at different times of imprisonment.ConclusionAt reception, particular attention should be paid to the following factors associated with early suicide events: widowed marital status, lack of prison experience, and drug dependency.

Preventive chemotherapy by mass drug administration is globally recommended as the primary method of reaching the elimination of schistosomiasis, especially in the high risk-paediatric population. This systematic review provides a summary of the effects of paediatric schistosomiasis control programs on eliminating schistosomiasis in sub-Saharan Africa. A systematic search was conducted in PubMed, EBSCOhost, and other databases to obtain studies regarding the effects of paediatric schistosomiasis control programmes in sub-Saharan Africa. 3455 studies were screened for eligibility, included articles reported on both paediatrics control programmes and schistosomiasis, and articles were excluded when they did not report on schistosomiasis control programmes in paediatrics exclusively. 40 selected studies were critically appraised using the JBI critical appraisal tools for relevance and 30 studies were included in the study. An in-depth quantitative descriptive analysis was conducted, and a comprehensive narrative summary explained the results within the scope of the review questions. The results show that despite preventive chemotherapy lowering schistosomiasis prevalence, chances of re-infection are high in endemic areas. Preventive chemotherapy without complementary interventions including safe water provision and proper sanitation, snail control and health education on the aetiology of schistosomiasis, transmission pattern and control practices might not eliminate schistosomiasis. [ABSTRACT FROM AUTHOR]

BackgroundDirect oral anticoagulants (DOACs) are administered in fixed doses without monitoring. There is still little published data on the impact of the absence of monitoring on adherence to medication and stability of DOAC plasma levels over time.ObjectivesTo explore adherence and stability of DOAC plasma levels over time in patients with atrial fibrillation (NVAF) recently started on DOAC therapy.Patients and methodsA prospective observational cohort study with structured follow up including assessment of adherence to medication, plasma levels at baseline, 3,6 and 12 months and adverse events.ResultsWe included 164 patients; 89% were previous users of a vitamin K antagonist (VKA). One-year adherence was reasonably good: Morisky adherence measurement scores of 6-8 in 92%. The majority of DOAC plasma levels were within reported on-therapy ranges; dabigatran (median 104.4 ng/ml, IQR 110.2), rivaroxaban (median 185.2 ng/ml, IQR 216.1) and on average levels were not different for full and adjusted doses. There was significant variation between patients, but no significant differences over time within individuals. A substantial proportion of patients starting in the upper-or lower 20th percentiles remained there during the entire follow up. Seventeen bleedings (16 minor, 1 major) were reported, no ischemic events and bleeding or thrombotic events were not associated with DOAC plasma levels.ConclusionsAdherence was reasonably good in the majority of patients. Our data confirm the stability of DOAC plasma levels over time. Knowledge of such data may, in the individual patient, contribute to optimal drug and dose selection.

Marine protected areas (MPAs) are valuable tools for marine conservation that aim to limit human impacts on marine systems and protect valuable species or habitats. However, as species distributions shift due to ocean warming, acidification, and oxygen depletion from climate change, the areas originally designated under MPAs may bear little resemblance to their past state. Different approaches have been suggested for coping with species on the move in conservation. Here, we test the effectiveness of different MPA designs, including dynamic, network, and different directional orientations on protecting shifting species under climate change through ecosystem modeling in a theoretical ecosystem. Our findings suggest that dynamic MPAs may benefit some species (e.g., whiting and anchovy) and fishing fleets, and these benefits can inform the design or adaptation of MPAs worldwide. In addition, we find that it is important to design MPAs with specific goals and to account for the effects of released fishing pressure and species interactions in MPA design.