Oxygen targets in the intensive care unit during mechanical ventilation for acute respiratory distress syndrome: a rapid review

BACKGROUND: Supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required.OBJECTIVES: To address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life.SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs).SELECTION CRITERIA: Two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask.DATA COLLECTION AND ANALYSIS: One review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy.MAIN RESULTS: We identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported.AUTHORS' CONCLUSIONS: We are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.</p

Coronary artery calcification on routine CT has prognostic and treatment implications for all ages

Aims: Guidelines have recommended reporting coronary artery calcification (CAC) if present on chest CT imaging regardless of indication. This study assessed CAC prevalence, prognosis and the potential clinical impact of its reporting. Methods: We performed a single-centre retrospective analysis (January-December 2015) of 1400 chest CTs (200 consecutive within each age group: &lt;40, 40-49, 50-59, 60-69, 70-79, 80-89, ≥90). CTs were re-reviewed for CAC presence and severity and excluded if prior coronary intervention. Comorbidities, statin prescription and clinical outcomes (myocardial infarction [MI], stroke, all-cause mortality) were recorded. The impact of reporting CAC was assessed against pre-existing statin prescriptions. Results: 1343 patients were included (mean age 63±20 years, 56% female). Inter- and intra-observer variability for CAC presence at re-review was almost perfect (κ 0.89, p &lt; 0.001; κ 0.90, p &lt; 0.001) and for CAC grading was substantial and almost perfect (κ 0.68, p &lt; 0.001; κ 0.91, p &lt; 0.001). CAC was observed in 729/1343 (54%), more frequently in males (p &lt; 0.001) and rising age (p &lt; 0.001). A high proportion of patients with CAC in all age groups had no prior statin prescription (range: 42% [80-89] to 100% [&lt;40]). The ‘number needed to report’ CAC presence to potentially impact management across all ages was 2. 689 (51%) patients died (median follow-up 74-months). CAC presence was associated with risk of MI, stroke and all-cause mortality (p &lt; 0.001). After adjusting for confounders, severe calcification predicted risk of all-cause mortality (HR 1.8 [1.2-2.5], p = 0.002). Conclusion: Grading of CAC was reproducible, and although prevalence rose with age, prognostic and treatment implications were maintained in all ages.</p

Coronary artery calcification on routine CT has prognostic and treatment implications for all ages

Aims: Guidelines have recommended reporting coronary artery calcification (CAC) if present on chest CT imaging regardless of indication. This study assessed CAC prevalence, prognosis and the potential clinical impact of its reporting. Methods: We performed a single-centre retrospective analysis (January-December 2015) of 1400 chest CTs (200 consecutive within each age group: &lt;40, 40-49, 50-59, 60-69, 70-79, 80-89, ≥90). CTs were re-reviewed for CAC presence and severity and excluded if prior coronary intervention. Comorbidities, statin prescription and clinical outcomes (myocardial infarction [MI], stroke, all-cause mortality) were recorded. The impact of reporting CAC was assessed against pre-existing statin prescriptions. Results: 1343 patients were included (mean age 63±20 years, 56% female). Inter- and intra-observer variability for CAC presence at re-review was almost perfect (κ 0.89, p &lt; 0.001; κ 0.90, p &lt; 0.001) and for CAC grading was substantial and almost perfect (κ 0.68, p &lt; 0.001; κ 0.91, p &lt; 0.001). CAC was observed in 729/1343 (54%), more frequently in males (p &lt; 0.001) and rising age (p &lt; 0.001). A high proportion of patients with CAC in all age groups had no prior statin prescription (range: 42% [80-89] to 100% [&lt;40]). The ‘number needed to report’ CAC presence to potentially impact management across all ages was 2. 689 (51%) patients died (median follow-up 74-months). CAC presence was associated with risk of MI, stroke and all-cause mortality (p &lt; 0.001). After adjusting for confounders, severe calcification predicted risk of all-cause mortality (HR 1.8 [1.2-2.5], p = 0.002). Conclusion: Grading of CAC was reproducible, and although prevalence rose with age, prognostic and treatment implications were maintained in all ages.</p

Binets: fundamental building blocks for phylogenetic networks

Phylogenetic networks are a generalization of evolutionary trees that are used by biologists to represent the evolution of organisms which have undergone reticulate evolution. Essentially, a phylogenetic network is a directed acyclic graph having a unique root in which the leaves are labelled by a given set of species. Recently, some approaches have been developed to construct phylogenetic networks from collections of networks on 2- and 3-leaved networks, which are known as binets and trinets, respectively. Here we study in more depth properties of collections of binets, one of the simplest possible types of networks into which a phylogenetic network can be decomposed. More speci_cally, we show that if a collection of level-1 binets is compatible with some binary network, then it is also compatible with a binary level-1 network. Our proofs are based on useful structural results concerning lowest stable ancestors in networks. In addition, we show that, although the binets do not determine the topology of the network, they do determine the number of reticulations in the network, which is one of its most important parameters. We also consider algorithmic questions concerning binets. We show that deciding whether an arbitrary set of binets is compatible with some network is at least as hard as the well-known Graph Isomorphism problem. However, if we restrict to level-1 binets, it is possible to decide in polynomial time whether there exists a binary network that displays all the binets. We also show that to _nd a network that displays a maximum number of the binets is NP-hard, but that there exists a simple polynomial-time 1/3-approximation algorithm for this problem. It is hoped that these results will eventually assist in the development of new methods for constructing phylogenetic networks from collections of smaller networks

Invited to labour or participate: intra- and inter-generational distinctions and the role of capital in children’s invited participation

This paper applies aspects of Bourdieu’s conceptual toolkit related to capital, and analyses inter- and intra-generational relations of influence. Applying Bourdieu’s concepts to examples of case studies from a children’s parliament in Finland, and with reference to an adult resident forum, moments of continuity and disruption in the relatively stable patterns of distinction between children and adults emerge. Children in school councils (at times) are labourers for agendas set by teachers, but the children at the top of the structure’s hierarchy can benefit from cultural capital and a functional capital that enables them to set agendas and direct the work of others. The political capital of the person presenting views from the participation sphere and the dominant symbolic capital of market logics appear to have a greater impact than generation on the influence participants achieve. Unquestioned acceptance of this differentiation suggests that new approaches to invited participation structures are needed

Health Visiting and School Nursing Programmes: supporting implementation of the new service model No.5: Domestic Violence and Abuse – Professional Guidance

Guidance created by an expert working group at the Department of Healt

Thinking about Later Life: Insights from the Capability Approach

A major criticism of mainstream gerontological frameworks is the inability of such frameworks to appreciate and incorporate issues of diversity and difference in engaging with experiences of aging. Given the prevailing socially structured nature of inequalities, such differences matter greatly in shaping experiences, as well as social constructions, of aging. I argue that Amartya Sen’s capability approach (2009) potentially offers gerontological scholars a broad conceptual framework that places at its core consideration of human beings (their values) and centrality of human diversity. As well as identifying these key features of the capability approach, I discuss and demonstrate their relevance to thinking about old age and aging. I maintain that in the context of complex and emerging identities in later life that shape and are shaped by shifting people-place and people-people relationships, Sen’s capability approach offers significant possibilities for gerontological research

Placebo and other psychological interactions in headache treatment

We present a theory according which a headache treatment acts through a specific biological effect (when it exists), a placebo effect linked to both expectancy and repetition of its administration (conditioning), and a non-specific psychological effect. The respective part of these components varies with the treatments and the clinical situations. During antiquity, suggestions and beliefs were the mainstays of headache treatment. The word placebo appeared at the beginning of the eighteenth century. Controversies about its effect came from an excessive interpretation due to methodological bias, inadequate consideration of the variation of the measure (regression to the mean) and of the natural course of the disease. Several powerful studies on placebo effect showed that the nature of the treatment, the associated announce, the patients’ expectancy, and the repetition of the procedures are of paramount importance. The placebo expectancy is associated with an activation of pre-frontal, anterior cingular, accumbens, and periacqueducal grey opioidergic neurons possibly triggered by the dopaminergic meso-limbic system. In randomized control trials, several arms design could theoretically give information concerning the respective part of the different component of the outcome and control the natural course of the disease. However, for migraine and tension type headache attacks treatment, no three arm (verum, placebo, and natural course) trial is available in the literature. Indirect evidence of a placebo effect in migraine attack treatment, comes from the high amplitude of the improvement observed in the placebo arms (28% of the patients). This figure is lower (6%) when using the harder criterium of pain free at 2 h. But these data disregard the effect of the natural course. For prophylactic treatment with oral medication, the trials performed in the last decades report an improvement in 21% of the patients in the placebo arms. However, in these studies the duration of administration was limited, the control of attacks uncertain as well as the evolution of the co-morbid psycho-pathology. Considering the reviews and meta-analysis of complex prophylactic procedures, it must be concluded that their effect is mostly linked to a placebo and non-specific psychological effects. Acupuncture may have a slight specific effect on tension type headache, but not on migraine. Manual therapy studies do not exhibit difference between manipulation, mobilization, and controls; touch has no proven specific effect. A comprehensive efficacy review of biofeedback studies concludes to a small specific effect on tension type headache but not on migraine. A review of behavioral treatment conclude to an interesting mean improvement but did not demonstrated a specific effect with the exception of a four arm study including a pseudo meditation control group. Expectation-linked placebo, conditioning, and non-specific psychological effects vary according clinical situations and psychological context; likely low in RCT, high after anempathic medical contact, and at its maximum with a desired charismatic healer. The announcements of doctors strongly influence the beliefs of patients, and in consequence their pain and anxiety sensibilities; this modulates the amplitude of the placebo and the non-specific psychological effects and is therefore a major determinant of the therapeutic success. Furthermore, any repetitive contact, even through a placebo, may interfere positively with the psychopathological co-morbidity. One has to keep in mind that the non-specific psychological interactions play a major role in the improvement of the majority of the headache sufferers

Indirect comparison of interventions using published randomised trials: systematic review of PDE-5 inhibitors for erectile dysfunction

BACKGROUND: There are no randomised and properly blinded trials directly comparing one PDE-5 inhibitor with another in a normal home setting. Valid indirect comparisons with a common comparator must examine equivalent doses, similar duration, similar populations, with the same outcomes reported in the same way. METHODS: Published randomised, double-blind trials of oral PDE-5 inhibitors for erectile dysfunction were sought from reference lists in previous reviews and electronic searching. Analyses of efficacy and harm were carried out for each treatment, and results compared where there was a common comparator and consistency of outcome reporting, using equivalent doses. RESULTS: Analysis was limited by differential reporting of outcomes. Sildenafil trials were clinically and geographically more diverse. Tadalafil and vardenafil trials tended to use enriched enrolment. Using all trials, the three interventions were similar for consistently reported efficacy outcomes. Rates of successful intercourse for sildenafil, tadalafil and vardenafil were 65%, 62%, and 59%, with placebo rates of 23–28%. The rates of improved erections were 76%, 75% and 71%, respectively, with placebo rates of 22–24%, and NNTs of 1.9 or 2.0. Reporting of withdrawals was less consistent, but all-cause withdrawals for sildenafil, tadalafil and vardenafil were 8% 13% and 20%. All three drugs were well tolerated, with headache being the most commonly reported event at 13–17%. There were few serious adverse events. CONCLUSION: There were differences between trials in outcomes reported, limiting comparisons, and the most useful outcomes were not reported. For common outcomes there was similar efficacy between PDE-5 inhibitors