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Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society.

Background: Caesarean section (CS) rates are rising. Shared decision making (SDM) is a component of patient-centered communication which requires adequate information and awareness. Women in Ghana have varying perceptions about the procedure. We sought to explore mothers’ knowledge. perceptions and SDM-influencing factors about CSs. Methods: A transdisciplinary mixed-methods study was conducted at the maternity unit of Korle-Bu Teaching Hospital in Accra, Ghana from March to May, 2019. Data collection was done in four phases: in-depth interviews (n = 38), pretesting questionnaires (n = 15), three focus group discussions (n = 18) and 180 interviewer administered questionnaires about SDM preferences. Factors associated with SDM were analyzed using Pearson’s Chi-square test and multiple logistic regression. Results: Mothers depicted a high level of knowledge regarding medical indications for their CS but had low level of awareness of SDM. The perception of a CS varied from dangerous, unnatural and taking away their strength to a life-saving procedure. The mothers had poor knowledge about pain relief in labour and at Caesarean section. Health care professionals attributed the willingness of mothers to be involved in SDM to their level of education. Husbands and religious leaders are key stakeholders in SDM. Insufficient consultation time was a challenge to SDM according to health care professionals and post-partum mothers. Women with parity ≥ 5 have a reduced desire to be more involved in shared decision making for Caesarean section. AOR = 0.09, CI (0.02–0.46). Conclusion: There is a high knowledge about the indications for CS but low level of awareness of and barriers to SDM. The fewer antenatal care visits mothers had, the more likely they were to desire more involvement in decision making. Aligned to respectful maternity care principles, greater involvement of pregnant women and their partners in decision making process could contribute to a positive pregnancy experience. Education, including religious leaders and decision- making tools could contribute to the process of SDM.

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

This review deals with an unwelcome reality about several forms of dementia, including Alzheimer’s disease— that these dementias are caused, in part or whole, by the aging of the vasculature. Since the vasculature ages in us all, dementia is our fate, sealed by the realit!ies of the circulation; it is not a disease with a cure pending. Empirically, cognitive impairment before our 7th decade is uncommon and considered early, while a diagnosis in our 11th decade is late but common in that cohort (>40%). Projections from earlier ages suggest that the prevalence of dementia in people surviving into their 12th decade exceeds 80%. We address the question why so few of many interventions known to delay dementia are recognized as therapy; and we try to resolve this few-and-many paradox, identifying opportunities for better treatment, especially pre-diagnosis. The idea of dementia as a fate is resisted, we argue, because it negates the hope of a cure. But the price of that hope is lost opportunity. An approach more in line with the evidence, and more likely to limit suffering, is to understand the damage that accumulates with age in the cerebral vasculature and therefore in the brain, and which eventually gives rise to cognitive symptoms in late life, too often leading to dementia. We argue that hope should be redirected to delaying that damage and with it the onset of cognitive loss; and, for each individual, it should be redirected to a life-long defense of their brain.

The COVID–19 pandemic led to local oxygen shortages worldwide. To gain a better understanding of oxygen consumption with different respiratory supportive therapies, we conducted an international multicenter observational study to determine the precise amount of oxygen consumption with high-flow nasal oxygen (HFNO) and with mechanical ventilation. A retrospective observational study was conducted in three intensive care units (ICUs) in the Netherlands and Spain. Patients were classified as HFNO patients or ventilated patients, according to the mode of oxygen supplementation with which a patient started. The primary endpoint was actual oxygen consumption; secondary endpoints were hourly and total oxygen consumption during the first two full calendar days. Of 275 patients, 147 started with HFNO and 128 with mechanical ventilation. Actual oxygen use was 4.9-fold higher in patients who started with HFNO than in patients who started with ventilation (median 14.2 [8.4–18.4] versus 2.9 [1.8–4.1] L/minute; mean difference = 11.3 [95% CI 11.0–11.6] L/minute; P < 0.01). Hourly and total oxygen consumption were 4.8-fold (P < 0.01) and 4.8-fold (P < 0.01) higher. Actual oxygen consumption, hourly oxygen consumption, and total oxygen consumption are substantially higher in patients that start with HFNO compared with patients that start with mechanical ventilation. This information may help hospitals and ICUs predicting oxygen needs during high-demand periods and could guide decisions regarding the source of distribution of medical oxygen.

Background Cluster-C personality disorders (PDs), characterized by a high level of fear and anxiety, are related to high levels of distress, societal dysfunctioning and chronicity of various mental health disorders. Evidence for the optimal treatment is extremely scarce. Nevertheless, the need to treat these patients is eminent. In clinical practice, group therapy is one of the frequently offered approaches, with two important frameworks: schema therapy and psychodynamic therapy. These two frameworks suggest different mechanisms of change, but until now, this has not yet been explored. The purpose of the present G-FORCE trial is to find evidence on the differential (cost)effectiveness of two forms of schema group therapy and psychodynamic group therapy in the routine clinical setting of an outpatient clinic and to investigate the underlying working mechanisms and predictors of outcome of these therapies. Methods In this mono-centre pragmatic randomized clinical trial, 290 patients with Cluster-C PDs or other specified PD with predominantly Cluster-C traits, will be randomized to one of three treatment conditions: group schema therapy for Cluster-C (GST-C, 1 year), schema-focused group therapy (SFGT, 1.5 year) or psychodynamic group therapy (PG, 2 years). Randomization will be pre-stratified on the type of PD. Change in severity of PD (APD-IV) over 24 months will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Potential predictors and mediators are selected and measured repeatedly. Also, a cost-effectiveness study will be performed, primarily based on a societal perspective, using both clinical effects and quality-adjusted life years. The time-points of assessment are at baseline, start of treatment and after 1, 3, 6, 9, 12, 18, 24 and 36 months. Discussion This study is designed to evaluate the effectiveness and cost-effectiveness of three formats of group psychotherapy for Cluster-C PDs. Additionally, predictors, procedure and process variables are analysed to investigate the working mechanisms of the therapies. This is the first large RCT on group therapy for Cluster-C PDs and will contribute improving the care of this neglected patient group. The absence of a control group can be considered as a limitation. Trial registration CCMO, NL72826.029.20. Registered on 31 August 2020, first participant included on 18 October 2020.

Background Cluster-C personality disorders (PDs) are highly prevalent in clinical practice and are associated with unfavourable outcome and chronicity of all common mental health disorders (e.g. depression and anxiety disorders). Although several forms of individual psychotherapy are commonly offered in clinical practice for this population, evidence for differential effectiveness of different forms of psychotherapy is lacking. Also, very little is known about the underlying working mechanisms of these psychotherapies. Finding evidence on the differential (cost)-effectiveness for this group of patients and the working mechanisms of change is important to improve the quality of care for this vulnerable group of patients. Objective In this study, we will compare the differential (cost)-effectiveness of three individual psychotherapies: short-term psychodynamic supportive psychotherapy (SPSP), affect phobia therapy (APT) and schema therapy (ST). Although these psychotherapies are commonly used in clinical practice, evidence for the Cluster-C PDs is limited. Additionally, we will investigate predictive factors, non-specific and therapy-specific mediators. Methods This is a mono-centre randomized clinical trial with three parallel groups: (1) SPSP, (2) APT, (3) ST. Randomization on patient level will be pre-stratified according to type of PD. The total study population to be included consists of 264 patients with Cluster-C PDs or other specified PD with mainly Cluster-C traits, aged 18–65 years, seeking treatment at NPI, a Dutch mental health care institute specialized in PDs. SPSP, APT and ST (50 sessions per treatment) are offered twice a week in sessions of 50 min for the first 4 to 5 months. After that, session frequency decreases to once a week. All treatments have a maximum duration of 1 year. Change in the severity of the PD (ADP-IV) will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Several potential mediators, predictors and moderators of outcome are also assessed. The effectiveness study is complemented with a cost-effectiveness/utility study, using both clinical effects and quality-adjusted life-years, and primarily based on a societal approach. Assessments will take place at baseline, start of treatment and at 1, 3, 6, 9, 12, 18, 24 and 36 months. Discussion This is the first study comparing psychodynamic treatment to schema therapy for Cluster-C PDs. The naturalistic design enhances the clinical validity of the outcome. A limitation is the lack of a control group for ethical reasons. Trial registration NL72823.029.20 [Registry ID: CCMO]. Registered on 31 August 2020. First participant included on 23 October 2020.

Dam failures that cause significant adverse downstream impacts continue to occur globally. Hence, effective, adequately resourced dam safety regulation is critical for the safety of dams and downstream communities. This paper explores options for regulatory funding and resourcing according to a selected set of relevant key factors along a continuum of dam safety assurance. An international comparative analysis of 15 jurisdictional case studies against the key factors identifies trends representing indicative precedents. A procedure is developed to help identify increasingly relevant precedents for guiding target jurisdictions on potentially suitable options. Illustrative application to a real case in Australia is provided. Refereed/Peer-reviewed

Background Ovarian cancers are hallmarked by chromosomal instability. New therapies deliver improved patient outcomes in relevant phenotypes, however therapy resistance and poor long-term survival signal requirements for better patient preselection. An impaired DNA damage response (DDR) is a major chemosensitivity determinant. Comprising five pathways, DDR redundancy is complex and rarely studied alongside chemoresistance influence from mitochondrial dysfunction. We developed functional assays to monitor DDR and mitochondrial states and trialled this suite on patient explants. Methods We profiled DDR and mitochondrial signatures in cultures from 16 primary-setting ovarian cancer patients receiving platinum chemotherapy. Explant signature relationships to patient progression-free (PFS) and overall survival (OS) were assessed by multiple statistical and machine-learning methods. Results DR dysregulation was wide-ranging. Defective HR (HRD) and NHEJ were near-mutually exclusive. HRD patients (44%) had increased SSB abrogation. HR competence was associated with perturbed mitochondria (78% vs 57% HRD) while every relapse patient harboured dysfunctional mitochondria. DDR signatures classified explant platinum cytotoxicity and mitochondrial dysregulation. Importantly, explant signatures classified patient PFS and OS. Conclusions Whilst individual pathway scores are mechanistically insufficient to describe resistance, holistic DDR and mitochondrial states accurately predict patient survival. Our assay suite demonstrates promise for translational chemosensitivity prediction.

Background: Prolonged second stage of labour is an important cause of maternal and perinatal morbidity and mortality. Vacuum extraction (VE) and second-stage caesarean section (SSCS) are the most commonly performed obstetric interventions, but the procedure chosen varies widely globally. Objectives: To compare maternal and perinatal morbidity, mortality and other adverse outcomes after VE versus SSCS. Search Strategy: A systematic search was conducted in PubMed, Cochrane and EMBASE. Studies were critically appraised using the Newcastle–Ottawa scale. Selection Criteria: All artictles including women in second stage of labour, giving birth by vacuum extraction or cesarean section and registering at least one perinatal or maternal outcome were selected. Data Collection and Analysis: The chi-square test, Fisher exact's test and binary logistic regression were used and various adverse outcome scores were calculated to evaluate maternal and perinatal outcomes. Main Results: Fifteen articles were included, providing the outcomes for a total of 20 051 births by SSCS and 32 823 births by VE. All five maternal deaths resulted from complications of anaesthesia during SSCS. In total, 133 perinatal deaths occurred in all studies combined: 92/20 051 (0.45%) in the SSCS group and 41/32 823 (0.12%) in the VE group. In studies with more than one perinatal death, both conducted in low-resource settings, more perinatal deaths occurred during the decision-to-birth interval in the SSCS group than in the VE group (5.5% vs 1.4%, OR 4.00, 95% CI 1.17–13.70; 11% vs 8.4%, OR 1.39, 95% CI 0.85–2.26). All other adverse maternal and perinatal outcomes showed no statistically significant differences. Conclusions: Vacuum extraction should be the recommended mode of birth, both in high-income countries and in low- and middle-income countries, to prevent unnecessary SSCS and to reduce perinatal and maternal deaths when safe anaesthesia and surgery is not immediately available.

This manuscript provides an overview of the current state of the art in terms of the molecular modelling of the thermophysical properties of fluids. It is intended to manage the expectations and serve as guidance to practising physical chemists, chemical physicists and engineers in terms of the scope and accuracy of the more commonly available intermolecular potentials along with the peculiarities of the software and methods employed in molecular simulations while providing insights on the gaps and opportunities available in this field. The discussion is focused around case studies which showcase both the precision and the limitations of frequently used workflows.

First established in the seventies, proteomics, chemoproteomics, and most recently, spatial/proximity-proteomics technologies have empowered researchers with new capabilities to illuminate cellular communication networks that govern sophisticated decision-making processes. With an ever-growing inventory of these advanced proteomics tools, the onus is upon the researchers to understand their individual advantages and limitations, such that we can ensure rigorous implementation and conclusions derived from critical data interpretations backed up by orthogonal series of functional validations. This perspective-based on the authors' experience in applying varied proteomics workflows in complex living models-underlines key book-keeping considerations, comparing and contrasting most-commonly-deployed modern proteomics profiling technologies. We hope this article stimulates thoughts among expert users and equips new-comers with practical knowhow of what has become an indispensable tool in chemical biology, drug discovery, and broader life-science investigations.

Pulmonary edema is a central hallmark of acute respiratory distress syndrome (ARDS). Endothelial dysfunction and epithelial injury contribute to alveolar-capillary permeability but their differential contribution to pulmonary edema development remains understudied. Plasma levels of surfactant protein-D (SP-D), soluble receptor for advanced glycation end products (sRAGE), and angiopoietin-2 (Ang-2) were measured in a prospective, multicenter cohort of invasively ventilated patients. Pulmonary edema was quantified using the radiographic assessment of lung edema (RALE) and global lung ultrasound (LUS) score. Variables were collected within 48 h after intubation. Linear regression was used to examine the association of the biomarkers with pulmonary edema. In 362 patients, higher SP-D, sRAGE, and Ang-2 concentrations were significantly associated with higher RALE and global LUS scores. After stratification by ARDS subgroups (pulmonary, nonpulmonary, COVID, non-COVID), the positive association of SP-D levels with pulmonary edema remained, whereas sRAGE and Ang-2 showed less consistent associations throughout the subgroups. In a multivariable analysis, SP-D levels were most strongly associated with pulmonary edema when combined with sRAGE (RALE score: βSP-D = 6.79 units/log10 pg/mL, βsRAGE = 3.84 units/log10 pg/mL, R2 = 0.23; global LUS score: βSP-D = 3.28 units/log10 pg/mL, βsRAGE = 2.06 units/log10 pg/mL, R2 = 0.086), whereas Ang-2 did not further improve the model. Biomarkers of epithelial injury and endothelial dysfunction were associated with pulmonary edema in invasively ventilated patients. SP-D and sRAGE showed the strongest association, suggesting that epithelial injury may form a final common pathway in the alveolar-capillary barrier dysfunction underlying pulmonary edema.

The hydration behaviour of coordination complexes is important for understanding their roles as bio-imaging agents. Determination of hydration is difficult, and various optical and NMR-based techniques have been used. Here we use EPR spectroscopy to unambiguously demonstrate that a t-butyl-pyridyl-functionalised ErIII DOTA derivative coordinates water, while its methylphosphinate analogue does not.

Objective: Extubation failure in brain-injured patients is associated with increased morbidity. Our objective was to systematically review prognostic factors associated with extubation failure in acutely brain-injured adult patients receiving invasive ventilation in an ICU. Data Sources: MEDLINE, Embase, and Cochrane Central were searched from inception to January 31, 2022. Study Selection: Two reviewers independently screened citations and selected English-language cohort studies and randomized trials examining the association of prognostic factors with extubation failure. Studies were considered if they included greater than or equal to 80% adult patients with acute brain injury admitted to the ICU and mechanically ventilated for greater than or equal to 24 hours. Data Extraction: Two reviewers extracted data on population, prognostic factors, extubation outcomes, and risk of bias (using the quality in prognostic factors tool). Data Synthesis: In the primary analysis, adjusted odds ratios (aOR) for each prognostic factor were pooled using random-effects models. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. The search identified 7,626 citations, of which 21 studies met selection criteria. Moderate-certainty evidence suggested increased risk of extubation failure with older age (aOR, 3.0 for upper vs lower tertile; 95% CI, 1.78-5.07) and longer duration of mechanical ventilation (aOR, 3.47 for upper vs lower tertile; 95% CI, 1.68-7.19). Presence of cough (aOR, 0.40; 95% CI, 0.28-0.57) and intact swallow (aOR, 0.34; 95% CI, 0.21-0.54) probably decreased risk of extubation failure (moderate certainty). Associations of other factors with extubation failure were informed by low or very low certainty evidence. Conclusions: Patient age, duration of mechanical ventilation, and airway reflexes were associated with extubation failure in brain-injured patients with moderate certainty. Future studies are needed to determine the optimal application of these variables in clinical practice.

WWOX biallelic loss-of-function pathogenic single nucleotide variants (SNVs) and copy number variants (CNVs) including exonic deletions and duplications cause WWOX-related epileptic encephalopathy (WOREE) syndrome. This disorder is characterized by refractory epilepsy, axial hypotonia, peripheral hypertonia, progressive microcephaly, and premature death. Here we report five patients with WWOX biallelic predicted null variants identified by exome sequencing (ES), genome sequencing (GS), and/or chromosomal microarray analysis (CMA). SNVs and intragenic deletions of one or more exons were commonly reported in WOREE syndrome patients which made the genetic diagnosis challenging and required a combination of different diagnostic technologies. These patients presented with severe, developmental and epileptic encephalopathy (DEE), and other cardinal features consistent with WOREE syndrome. This report expands the clinical phenotype associated with this condition, including failure to thrive in most patients and epilepsy that responded to a ketogenic diet in three patients. Dysmorphic features and abnormal prenatal findings were not commonly observed. Additionally, recurrent pancreatitis and sensorineural hearing loss each were observed in single patients. In summary, these phenotypic features broaden the clinical spectrum of WOREE syndrome.

Multilocular adipocytes are a hallmark of thermogenic adipose tissue(1,2), but the factors that enforce this cellular phenotype are largely unknown. Here, we show that an adipocyte-selective product of the Clstn3 locus (CLSTN3β) present in only placental mammals facilitates the efficient use of stored triglyceride by limiting lipid droplet (LD) expansion. CLSTN3β is an integral endoplasmic reticulum (ER) membrane protein that localizes to ER–LD contact sites through a conserved hairpin-like domain. Mice lacking CLSTN3β have abnormal LD morphology and altered substrate use in brown adipose tissue, and are more susceptible to cold-induced hypothermia despite having no defect in adrenergic signalling. Conversely, forced expression of CLSTN3β is sufficient to enforce a multilocular LD phenotype in cultured cells and adipose tissue. CLSTN3β associates with cell death-inducing DFFA-like effector proteins and impairs their ability to transfer lipid between LDs, thereby restricting LD fusion and expansion. Functionally, increased LD surface area in CLSTN3β-expressing adipocytes promotes engagement of the lipolytic machinery and facilitates fatty acid oxidation. In human fat, CLSTN3B is a selective marker of multilocular adipocytes. These findings define a molecular mechanism that regulates LD form and function to facilitate lipid utilization in thermogenic adipocytes.

Este trabalho investiga o lugar do tráfico na história política de Pernambuco entre 1817 e os anos 1840, através da trajetória de dois grandes traficantes, pai e filho, que operavam a partir do Recife e de seu engenho na zona da mata – um dos maiores da província. Ambos estiveram sempre do lado monarquista e conservador na política provincial. O pai, português, chegou a ser preso pelo governo republicano de 1817. O filho não era branco, mas ocupou posição destacada no corpo do comércio do Recife e casou com a filha de outro grande negociante de cativos, constituindo talvez a família mais abastada da província. Na escala atlântica, Pernambuco está em quarto lugar entre os locais que mais receberam cativos da África entre os séculos XVI e XIX. O estudo dessas trajetórias, portanto, ajuda a entender o papel político dos traficantes e suas redes no contexto da Independência e da transição para negócios legais depois de 1831.

Parasympathetic nerve-mediated contractions of detrusor smooth muscle are generated by ATP and acetylcholine (ACh) release from efferent nerve terminals. In humans, ACh is responsible for detrusor contractions in normal human bladders, whereas ATP has an additional role in overactive bladder pathologies. The ATP metabolite, adenosine, relaxes nerve-mediated contractions, with a potential action via presynaptic adenosine A1 receptor activation and subsequent suppression of neuronal ATP release. We investigated the effect of A1 receptor activation and downstream cAMP-dependent pathways on nerve-mediated ATP and ACh release, and detrusor contraction in mouse detrusor. Bladders from male C57BL/6 mice (12 wk) were used for in vitro experiments. Upon electrical field stimulation of intact preparations (detrusor and mucosal layers), ATP or ACh release was measured simultaneously with tension recordings. Activation of A1 receptors by adenosine or exogenous agonists reduced the lower frequency component of nerve-mediated contractions and neuronal ATP release. The A1 receptor antagonist abolished these effects. A1 receptor activation inhibits adenylyl cyclase (AC) activity and cAMP generation. The effect of A1 receptor activation was mimicked by a PKA antagonist but not by modulators of exchange proteins activated by cAMP, demonstrating that modulation of nerve-mediated ATP release is via PKA. Adenosine had no effect on ACh release or the higher frequency component of nerve-mediated contractions. Differential regulation of neurotransmitter release is possible at the detrusor nerve-muscle junction, as demonstrated by A1 receptor activation, and downstream inhibition of AC, cAMP generation, and PKA. The ability to specifically attenuate ATP release offers a potential to target purinergic motor pathways enhanced in overactive bladder pathologies.

Background: No international data are available on the night working conditions and workload of anaesthesiologists and their opinions about associated risks. Objective: The aim of this international survey was to describe the peri-operative night working conditions of anaesthesiologists and their perception of the impact these conditions have on patient outcomes and their own quality of life. Design: Cross-sectional survey. Setting: Not applicable. Participants: Anaesthesiologists providing peri-operative care during night shifts responded to an online survey promoted by the European Society of Anaesthesiology and Intensive Care (ESAIC). Interventions: None. Main outcome measure: Twenty-eight closed questions. Results: Overall 5292 complete responses were analysed. Of these, 920 were from trainees. The median reported monthly number of night shifts was 4 [IQR 3-6]. An irregular weekly night shift schedule was most common (51%). Almost all the respondents (98%) declared that their centres have no relevant institutional programmes to monitor stress or fatigue. Most respondents (90%) had received no training or information regarding performance improvement methods for night work. Most respondents were of the opinion that sleep deprivation affects their professional performance (71%) and that their fatigue during night work may increase the peri-operative risk for their patients (74%). Furthermore, 81% of the respondents agreed or strongly agreed that night work represents an additional risk per se for patient safety, and 77% stated that their night work affects the quality of their daily life significantly or extremely. Conclusion: Anaesthesiologists commonly perform perioperative night work without appropriate training, education or support on this specific condition. They perceive current practice as adversely affecting their professional performance and the safety of their patients. They also report significant effects on their own quality of life. Adequate training and education for night work may ally some of these concerns and programmes to monitor workers' stress and fatigue should be mandated to assess whether these concerns are justified. Trial registration: Not applicable.

The human gut microbiome is a complex ecosystem of microorganisms that play an important role in human health, influencing functions such as vitamin uptake, digestion and immunomodulation. While research of the gut microbiome has expanded considerably over the past decade, some areas such as the relationship between exercise and the microbiome remain relatively under investigated. Despite this, multiple studies have shown a potential bidirectional relationship between exercise and the gut microbiome, with some studies demonstrating the possibility of influencing this relationship. This, in turn, could provide a useful route to influence athletic performance via microbiome manipulation, a valuable prospect for many elite athletes and their teams. The evidence supporting the potential benefits of pursuing this route and associated future perspectives are discussed in this review.

Background: Childhood trauma is a common and potent risk factor for developing major depressive disorder in adulthood, associated with earlier onset, more chronic or recurrent symptoms, and greater probability of having comorbidities. Some studies indicate that evidence-based pharmacotherapies and psychotherapies for adult depression might be less efficacious in patients with a history of childhood trauma than patients without childhood trauma, but findings are inconsistent. Therefore, we examined whether individuals with major depressive disorder, including chronic forms of depression, and a reported history of childhood trauma, had more severe depressive symptoms before treatment, had more unfavourable treatment outcomes following active treatments, and were less likely to benefit from active treatments relative to a control condition, compared with individuals with depression without childhood trauma. Methods: We did a comprehensive meta-analysis (PROSPERO CRD42020220139). Study selection combined the search of bibliographical databases (PubMed, PsycINFO, and Embase) from Nov 21, 2013, to March 16, 2020, and full-text randomised clinical trials (RCTs) identified from several sources (1966 up to 2016–19) to identify articles in English. RCTs and open trials comparing the efficacy or effectiveness of evidence-based pharmacotherapy, psychotherapy, or combination intervention for adult patients with depressive disorders and the presence or absence of childhood trauma were included. Two independent researchers extracted study characteristics. Group data for effect-size calculations were requested from study authors. The primary outcome was depression severity change from baseline to the end of the acute treatment phase, expressed as standardised effect size (Hedges' g). Meta-analyses were done using random-effects models. Findings: From 10 505 publications, 54 trials met the inclusion criteria, of which 29 (20 RCTs and nine open trials) contributed data of a maximum of 6830 participants (age range 18–85 years, male and female individuals and specific ethnicity data unavailable). More than half (4268 [62%] of 6830) of patients with major depressive disorder reported a history of childhood trauma. Despite having more severe depression at baseline (g=0·202, 95% CI 0·145 to 0·258, I2=0%), patients with childhood trauma benefitted from active treatment similarly to patients without childhood trauma history (treatment effect difference between groups g=0·016, –0·094 to 0·125, I2=44·3%), with no significant difference in active treatment effects (vs control condition) between individuals with and without childhood trauma (childhood trauma g=0·605, 0·294 to 0·916, I2=58·0%; no childhood trauma g=0·178, –0·195 to 0·552, I2=67·5%; between-group difference p=0·051), and similar dropout rates (risk ratio 1·063, 0·945 to 1·195, I2=0%). Findings did not significantly differ by childhood trauma type, study design, depression diagnosis, assessment method of childhood trauma, study quality, year, or treatment type or length, but differed by country (North American studies showed larger treatment effects for patients with childhood trauma; false discovery rate corrected p=0·0080). Most studies had a moderate to high risk of bias (21 [72%] of 29), but the sensitivity analysis in low-bias studies yielded similar findings to when all studies were included. Interpretation: Contrary to previous studies, we found evidence that the symptoms of patients with major depressive disorder and childhood trauma significantly improve after pharmacological and psychotherapeutic treatments, notwithstanding their higher severity of depressive symptoms. Evidence-based psychotherapy and pharmacotherapy should be offered to patients with major depressive disorder regardless of childhood trauma status. Funding: None.

Background. Diagnosing and discriminating non-cardiogenic interstitial syndrome (NCIS) and cardiogenic pulmonary edema (CPE) is notoriously difficult in a mixed intensive care unit (ICU) population. We hypothesized that a comprehensive lung ultrasound exam can be used to accurately diagnose interstitial syndrome and can discriminate between NCIS and CPE.Methods. A single center prospective diagnostic accuracy study was used as derivation cohort and a post-hoc analysis of a multi-center prospective observational study as validation cohort. Consecutive adult ICU patients that received a lung ultrasound examination for clinical or study purposes were included. The reference standard was the diagnosis interstitial syndrome (NCIS or CPE) or non-interstitial syndromes (other pulmonary diagnoses and no pulmonary diagnoses) at the moment of examination based on full post-hoc clinical chart review except lung ultrasound. The index test was a comprehensive lung ultrasound examination performed and scored by a researcher blinded to clinical information.Results. 101 patients were included in the derivation and 125 in validation cohort. In the derivation cohort, patients with interstitial syndrome (n=56) were reliably discriminated from other patients based on the presence of a B-pattern (defined as ≥3 B-lines in one frame) with an accuracy of 94.7% (sens 90.9%, spec 91.1%), while specificity was higher for a bilateral B-pattern (accuracy 86.0%; sens 74.5%, spec 100%). For the discrimination of NCIS (n=29) from CPE (n=27), the presence of bilateral pleural line abnormalities had the highest diagnostic accuracy (94.6%; sens 89.3%, spec 100%) followed by consolidation (76.8%; sens 69.0%, spec 85.2%) and subtle lung sliding (67.9%; sens 62.1%, spec 74.1%). A diagnostic algorithm (BLUISH protocol) using B-pattern and bilateral pleural abnormalities had an accuracy of 0.86 (95%CI 0.77-0.95) for diagnosis and discrimination of interstitial syndromes. In the validation cohort, which included 125 patients with interstitial syndrome, pleural line abnormalities discriminated NCIS (n=101) from CPE (n=24) with a sensitivity of 30% (95%CI 21-40%) and a specificity of 100% (95%CI: 86-100%). Conclusions. Lung ultrasound can be used to diagnose and discriminate interstitial syndromes in ICU patients with moderate to good accuracy. Pleural line abnormalities are highly specific for NCIS, but sensitivity is limited.

Variation in general practice (GP) referral rates to outpatient services is well described however variance in rates of referral to acute medical units is lacking.To investigate variance in GP referral rate for acute medical assessment and subsequent need for hospital admission.A retrospective cohort study of acute medical referrals from 88 GPs in Lothian, Scotland between 2017 and 2020 was performed using practice population size, age, deprivation, care home residence, and distance from hospital as explanatory variables. Patient-level analysis of demography, deprivation, comorbidity, and acuity markers was subsequently performed on referred and clinically assessed acute medical patients (n = 42,424) to examine how practice referral behaviour reflects clinical need for inpatient hospital care.Variance in GP referral rates for acute medical assessment was high (2.53-fold variation 1st vs. 4th quartile) and incompletely explained by increasing age and deprivation (adjusted R2 0.67, P0.001) such that significant variance remained after correction for confounders (2.15-fold). Patients from the highest referring quartile were significantly less likely to require hospital admission than those from the third, second, or lowest referring quartiles (adjusted odds ratio 1.28 [1.21-1.36, P0.001]; 1.30 [1.23-1.37, P0.001]; 1.53 [1.42-1.65, P0.001]).High variation in GP practice referral rate for acute medical assessment is incompletely explained by practice population socioeconomic factors and negatively associates with need for urgent inpatient care. Identifying modifiable factors influencing referral rate may provide opportunities to facilitate community-based care and reduce congestion on acute unscheduled care pathways.Managing the populations need for urgent medical care is challenge in many healthcare systems and overcrowding of urgent medical services negatively affects patient experience and can affect timely treatment. In the United Kingdom, the primary sources of patients attending for acute medical care are self-attendance to the hospital or by way of referral by a primary care physician (general practitioner). These data for the first time demonstrate high variation in referral rates for acute medical assessment between general practices which is incompletely explained by factors such as the age, deprivation, distance to the hospital or care home residence status of the care home population. Analysis of over 40,000 of these referrals for urgent medical care was subsequently undertaken to further investigate this variation. After adjusting for important clinical factors, patients referred from “high referring” practices were over 50% less likely to require inpatient hospital care than patients from lower referring practices. This suggests that the threshold for referral varies greatly between individual primary care clinicians, practices, or practice populations and many of these patients may have been suitable for less urgent community-based care. Identification of modifiable factors that account for this unexplained variation may facilitate community-based care and improve patient experience by reducing unnecessary attendance and congestion in already busy emergency care services.

The development of detailed national pathways towards sustainable food and land systems aims to provide stakeholders with clarity on how long-term goals could be achieved and to reduce roadblocks in the way to making commitments. However, the inability to perfectly capture the relationships between all variables in a system and the unknown probability of future values (deep uncertainty) makes it very difficult to design scenarios that account for the full breadth of system uncertainty. Here we use scenario discovery to systematically explore the effect of different parameter ranges on model outputs, and design resilient pathways to sustainability in which multiple target achievement requires a broad portfolio of solutions. We use a model of the Australian food and land system, the FABLE (Food, Agriculture, Biodiversity, Land-use, Energy) Calculator, to investigate conditions for achieving a sustainable Australian food and land system under scenarios based on the Shared Socioeconomic Pathways (SSP) 1, 2, and 3 narratives. Here we link the FABLE Calculator with a Monte Carlo simulation tool to explore hundreds of thousands of scenarios. This allows us to identify the ranges of systemic drivers that achieve multiple sustainability targets around diets, net forest growth, agricultural water consumption, greenhouse gas emissions, biodiversity conservation, and exports by 2050. Our results show that livestock productivity and density, afforestation, and dietary change are powerful influencers for sustainability target achievement. Around 10% of the SSP1 scenarios could achieve all modelled sustainability targets. However, practically none of the scenarios based on SSP2 and SSP3 narratives could achieve such targets. The results suggest that there are options to achieve a more sustainable and resilient Australian food and land-use system with better socio-economic and environmental outcomes than under current trends. However, its achievement requires significant structural changes and coordinated interventions in several components of the domestic food and land system to increase its resilience and environmental and socio-economic performance. Understanding the bounds within which this system needs to change and operate to achieve sustainability targets will enable greater clarity and flexibility during discussions between decision-makers and stakeholders.The online version contains supplementary material available at 10.1007/s11625-022-01202-2.

Chronic pain represents a global health problem with a considerable economic burden. The relation of alcohol intake and chronic pain conditions was assessed in several studies with conflicting results. We used dose-response meta-analysis techniques to answer the question of whether alcohol intake is related to chronic pain occurrence.We searched MEDLINE, Embase, and other databases to identify cohort and case-control studies on alcohol consumption and chronic pain. Sixteen studies were eligible with a total population of 642 587 individuals. Fixed-effects and random-effects pooled estimates were obtained by weighting log odds ratios (ORs) in case-control studies and log incidence rate ratios in cohort studies by the inverse of their variance. A heterogeneity assessment and a dose-response analysis were carried out. Quality scoring was also performed.Our results show that any alcohol consumption was related to lower odds of chronic pain (pooled OR=0.76; 95% confidence interval [CI], 0.61-0.95). The association was non-linear. The ORs by quartile of alcohol doses were as follows: ORAlcohol consumption presents a non-linear inverse association with the occurrence of chronic pain. Although plausible mechanisms could explain this protective effect, other explanations, including reverse causation, are probable.

BackgroundIdentifying men whose lower urinary tract symptoms (LUTS) may benefit from surgery is challenging.ObjectiveTo identify routine diagnostic and urodynamic measures associated with treatment decision-making, and outcome, in exploratory analyses of the UPSTREAM trial.Design, setting, and participantsA randomised controlled trial was conducted including 820 men, considering surgery for LUTS, across 26 hospitals in England (ISCTRN56164274).InterventionMen were randomised to a routine care (RC) diagnostic pathway (n = 393) or a pathway that included urodynamics (UDS) in addition to RC (n = 427).Outcome measurements and statistical analysisMen underwent uroflowmetry and completed symptom questionnaires, at baseline and 18 mo after randomisation. Regression models identified baseline clinical and symptom measures that predicted recommendation for surgery and/or surgical outcome (measured by the International Prostate Symptom Score [IPSS]). We explored the association between UDS and surgical outcome in subgroups defined by routine measures.Results and limitationsThe recommendation for surgery could be predicted successfully in the RC and UDS groups (area under the receiver operating characteristic curve 0.78), with maximum flow rate (Qmax) and age predictors in both groups. Surgery was more beneficial in those with higher symptom scores (eg, IPSS >16), age 47.6, and bladder contractility index >123.0. In the UDS group, urodynamic measures were more strongly predictive of surgical outcome for those with Qmax >15, although patient-reported outcomes were also more predictive in this subgroup.ConclusionsTreatment decisions were informed with UDS, when available, but without evidence of change in the decisions reached. Despite the small group sizes, exploratory analyses suggest that selective use of UDS could detect obstructive pathology, missed by routine measures, in certain subgroups.Patient summaryBaseline clinical and symptom measurements were able to predict treatment decisions. The addition of urodynamic test results, while useful, did not generally lead to better surgical decisions and outcomes over routine tests alone.

Background: Sarcomas are rare, aggressive cancers which frequently metastasise to the lungs. Following diagnosis, patients typically undergo staging by means of a CT scan of their chest. This often identifies indeterminate pulmonary nodules (IPNs), but the significance of these in high-grade soft tissue sarcoma (STS) is unclear. Identifying whether these are benign or malignant is important for clinical decision making. This study analyses the clinical relevance of IPNs in high-grade STS. Methods: All patients treated at our centre for high-grade soft tissue sarcoma between 2010 and 2020 were identified from a prospective database. CT scans and their reports were reviewed, and survival data were collected from patient records. Results: 389 suitable patients were identified; 34.4% had IPNs on their CT staging scan and 20.1% progressed into lung metastases. Progression was more likely with IPNs ≥ 5 mm in diameter (p = 0.006), multiple IPNs (p = 0.013) or bilateral IPNs (p = 0.022), as well as in patients with primaries ≥ 5 cm (p = 0.014), grade 3 primaries (p = 0.009) or primaries arising deep to the fascia (p = 0.041). The median time to progression was 143 days. IPNs at diagnosis were associated with an increased risk of developing lung metastases and decreased OS in patients with grade 3 STS (p = 0.0019 and p = 0.0016, respectively); this was not observed in grade 2 patients. Conclusions: IPNs at diagnosis are associated with significantly worse OS in patients with grade 3 STS. It is crucial to consider the primary tumour as well as the IPNs when considering the risk of progression. Surveillance CT scans should be carried out within 6 months.

The aim of this analysis was to compare ventilation management and outcomes in invasively ventilated patients with acute hypoxemic respiratory failure due to coronavirus disease 2019 (COVID-19) between the first and second wave in the Netherlands. This is a post hoc analysis of two nationwide observational COVID-19 studies conducted in quick succession. The primary endpoint was ventilation management. Secondary endpoints were tracheostomy use, duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), and mortality. We used propensity score matching to control for observed confounding factors. This analysis included 1122 patients from the first and 568 patients from the second wave. Patients in the second wave were sicker, had more comorbidities, and had worse oxygenation parameters. They were ventilated with lower positive end-expiratory pressure and higher fraction inspired oxygen, had a lower oxygen saturation, received neuromuscular blockade more often, and were less often tracheostomized. Duration of ventilation was shorter, but mortality rates were similar. After matching, the fraction of inspired oxygen was lower in the second wave. In patients with acute hypoxemic respiratory failure due to COVID-19, aspects of respiratory care and outcomes rapidly changed over the successive waves.

Background: Ventilation with lower positive end–expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). Methods: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty–seven patients underwent a systematic 12–region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. Results: Thirty–three and twenty–four patients received ventilation with lower PEEP (median PEEP 1 (0–5) cm H2O) or higher PEEP (median PEEP 8 (8–8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (–2 to 3)) in the lower PEEP group, and 7 (2–11) and 6 (1–12) (difference 0 (–2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. Conclusions: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration.

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9J/min [IQR 9.2-15.1], 13J/min [IQR 10-17], and 14J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9J/min, aRR at 17J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation.

Fetal movement (FM) is a sign of fetal life and wellbeing that is felt by the pregnant woman, and reduced FM is known to precede stillbirths.1, 2 Therefore, healthcare providers may advise women to monitor and report if their babies’ movements are fewer than usual. In high-income countries (HICs), there has been a renewed interest in FM with a recent wave of large-scale randomised controlled clinical trials investigating its potential to reduce stillbirths. The My Baby’s Movement trial in Australia and New Zealand and the Mindfetalness trial in Sweden have investigated the effects of intervention aimed at increasing women’s awareness of FM.3, 4 In the UK, the AFFIRM trial investigated the effects of an FM awareness package coupled with a standardised management protocol.5 The ongoing CEPRA study in the Netherlands, UK and Australia aims to evaluate Cerebro Placental Ratio as an indicator for delivery in women with reduced FM.6 None of the completed trials, however, found significant reductions in stillbirths. Moreover, they showed conflicting results on some potential harmful consequences, such as increased rates of obstetric interventions. In this commentary, we reflect on these trials through a global lens, and we urgently call for more trials – but this time in settings suffering the majority (98%) of the world’s 2 million annual stillbirths

Background: Increased access and utilization of vision care services has the potential to reduce preventable vision loss. The state of Ohio has been uniquely proactive when collecting vision-oriented data through population health surveys, including the Behavioral Risk Factor Surveillance System (BRFSS). These data can be used to better understand vision care utilization patterns and access to insurance. Methods: Responses to 3 items administered in the Ohio BRFSS that assess vision care utilization and insurance coverage were compared between 2 different administration periods, 2005-2011 and 2018-2019, using chi-square tests. Comparable data from 2 items assessing eye care utilization were available in 2005-2011 and 2019. Comparable data for insurance coverage were available in 2005-2011 and in 2018-2019. Responses were further stratified by population characteristics, including age, gender, household income, and education level. Results: The percentages of those reporting eye exams in the previous year were not significantly different between 2005-2011 and 2019 (chi-square, p = 0.06). In Ohio, the primary reason for not seeing a vision care provider in the past 12 months was “No reason to go” in 2005-2011 and in 2019. The second most common reason for not seeing a vision care provider in the past 12 months was “Cost/insurance,” which decreased between 2005-2011 and 2019 (chi-square, p

This study aimed to differentiate peak ball speed during shooting and shoulder rotation strength of the dominant arm between previously injured (PI) and uninjured (UI) water polo players. Nine PI and nine UI players performed 10 shots at 6 m from the goal mouth and three sets of three repetitions of isokinetic shoulder strength tests at 180 degrees/s on a dynamometer. Peak ball speed and shoulder concentric internal rotation (CIR) and eccentric external rotation (EER) peak torque (PT) and total work (TW) normalised to body mass were measured. EER:CIR PT and TW ratios were calculated. All PI versus UI comparisons were made using an Independent Samples T-Test. PI players shot 6% faster, produced 18% more CIR PT, and had lower EER:CIR PT (22%) and TW (34%) ratios compared with UI players. Shoulder TW compared with PT ratios could be more sensitive in differentiating PI versus UI players as TW takes into account the muscles' capacity throughout full active ROM. Practitioners could expand their foci to monitor shoulder EER:CIR TW ratios, in addition to PT ratios, to identify muscle imbalances in water polo athletes who might be at risk of injury/reinjury, and thereafter design interventions to reduce these imbalances.

Background: Hospitalizations among skilled nursing facility (SNF) residents in Detroit increased in mid-March 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. Outbreak response teams were deployed from local healthcare systems, the Centers for Disease Control and Prevention (CDC), and the Detroit Health Department (DHD) to understand the infection prevention and control (IPC) gaps in SNFs that may have accelerated the outbreak. Methods: We conducted 2 point-prevalence surveys (PPS-1 and PPS-2) at 13 Detroit SNFs from April 8 to May 8, 2020. The DHD and partners conducted facility-wide severe acute respiratory coronavirus virus 2 (SARS-CoV-2) testing of all residents and staff and collected information regarding resident cohorting, staff cohorting, and personnel protective equipment (PPE) utilized during that time. Results: Resident cohorting had been implemented in 7 of 13 (58.3%) SNFs prior to point-prevalence survey 1 (PPS-1), and other facilities initiated cohorting after obtaining PPS-1 results. Cohorting protocols of healthcare practitioners and environmental service staff were not established in 4 (31%) of 13 facilities, and in 3 facilities (23.1%) the ancillary staff were not assigned to cohorts. Also, 2 SNFs (15%) had an observation unit prior to PPS-1, 2 (15%) had an observation unit after PPS-1, 4 (31%) could not establish an observation unit due to inadequate space, and 5 (38.4%) created an observation unit after PPS-2. Conclusion: On-site consultations identified gaps in IPC knowledge and cohorting that may have contributed to ongoing transmission of SARS-CoV-2 among SNF residents despite aggressive testing measures. Infection preventionists (IPs) are critical in guiding ongoing IPC practices in SNFs to reduce spread of COVID-19 through response and prevention.

Isometric strength training has been reported to benefit various sport-related dynamic performances. However, it is still unknown whether performing isometric strength training at single or multiple joint angles would elicit greater benefit. Purpose: To compare the effects of isometric bench press performed at single (SIBP) and multiple (MIBP) joint angles on dynamic strength and overhead throwing performance. Methods: Sixteen male softball and baseball athletes performed overhead throwing, 1-repetition-maximum (1RM) bench press, and ballistic push-up during pretest and posttest. They were then randomly assigned to either SIBP or MIBP to undergo 12 strength training sessions. During the training, isometric bench press was performed at only 90° elbow angle for SIBP but at 60°, 90°, and 120° elbow angles for MIBP. Results: A significant main time effect was observed for bench press 1RM (P = .003) and relative 1RM (P P = .037). There was no significant change in overhead throwing velocity in either group. There was also no significant difference in change in all measures between groups. However, a moderate effect in favor of MIBP was observed for change in ballistic push-up peak power (P = .180, g = 0.67). Conclusions: Based on the current findings, the inclusion of both SIBP and MIBP were equally beneficial to maximal strength development. However, performing MIBP had a greater effect on power development.

Purpose: Intensive care is a stressful environment in which team-family conflicts commonly occur. If managed poorly, conflicts can have negative effects on all parties involved. Previous studies mainly investigated these conflicts and their management in a retrospective way. This study aimed to prospectively explore team-family conflicts, including its main topics, complicating factors, doctors’ conflict management strategies and the effect of these strategies. Methods: Conversations between doctors in the neonatal, pediatric, and adult intensive care unit of a large university-based hospital and families of critically ill patients were audio-recorded from the moment doubts arose whether treatment was still in patients’ best interest. Transcripts were coded and analyzed using a qualitative deductive approach. Results: Team-family conflicts occurred in 29 out of 101 conversations (29%) concerning 20 out of 36 patients (56%). Conflicts mostly concerned more than one topic. We identified four complicating context- and/or family-related factors: diagnostic and prognostic uncertainty, families’ strong negative emotions, limited health literacy, and burden of responsibility. Doctors used four overarching strategies to manage conflicts, namely content-oriented, process-oriented, moral and empathic strategies. Doctors mostly used content-oriented strategies, independent of the intensive care setting. They were able to effectively address conflicts in most conversations. Yet, if they did not acknowledge families’ cues indicating the existence of one or more complicating factors, conflicts were likely to linger on during the conversation. Conclusion: This study underlines the importance of doctors tailoring their communication strategies to the concrete conflict topic(s) and to the context- and family-related factors which complicate a specific conflict.