Epidemiology of Pneumocystis jirovecii Pneumonia and (Non-)use of Prophylaxis

Objectives: Pneumocystis jirovecii pneumonia (PCP) is an AIDS-defining illness. In patients with HIV, the benefit of PCP prophylaxis is well-defined when the CD4 T-cell count decreases below 200 cells/μL. In other immunocompromised patients, the value of PCP prophylaxis is not always as well-established. This study aimed to describe the epidemiology of PCP in recent years and assess how many patients with PCP did or did not receive prophylaxis in the month preceding the infection. Material and Methods: A multicenter retrospective study was performed in 3 tertiary care hospital. A list of patients that underwent broncho-alveolar lavage sampling and Pneumocystis jirovecii (PJ) PCR testing was retrieved from the microbiology laboratories. An in-house PJ quantitative PCR (qPCR) was used in each center. A cycle threshold (Ct) value of ≤ 28.5–30 was considered a probable PCP. For patients with a positive PJ qPCR but above this threshold, a predefined case definition of possible PCP was defined as a qPCR Ct value ≤ 34–35 and both of the following criteria: 1. Clinical and radiological features compatible with PCP and 2. The patient died or received PCP therapy and survived. Patient files from those with a qPCR Ct value ≤ 35 were reviewed to determine whether the patient fulfilled the case definition and if PCP prophylaxis had been used in the weeks preceding the PCP. Disease-specific guidelines, as well as hospital-wide guidelines, were used to evaluate if prophylaxis could be considered indicated. Results: From 2012 to 2018, 482 BAL samples were tested. Two hundred and four had a qPCR Ct value ≤ 35 and were further evaluated: 90 fulfilled the definition of probable and 63 of possible PCP while the remaining 51 were considered colonized. Seventy-four percentages

Detecting head and neck lymph node metastases with white light reflectance spectroscopy; a pilot study

Introduction: A challenge in the treatment of patients with head and neck cancer is the management of occult cervical lymph node (LN) metastases. Single-fiber reflectance (SFR) spectroscopy has the potential to detect physiological tissue changes that occur in a positive LN. This pilot study aimed to investigate whether SFR spectroscopy could serve as an alternative or additional technique to detect cervical lymph node metastases. Materials and Methods: We performed intraoperative SFR spectroscopy measurements of LNs with and without malignancies. We analyzed if physiological and scattering parameters were significantly altered in positive LNs. Results: Nine patients with a total of nineteen LNs were included. Three parameters, blood volume fraction (BVF), microvascular saturation (StO2), and Rayleigh amplitude, were significantly lower in positive LNs. They were combined into one optical parameter ‘delta’, using discriminant analysis. Delta was significantly decreased in positive LNs, p = 0,0006. It had a high diagnostic accuracy where the sensitivity, specificity, PPV, and NPV were 90,0%, 88.9%, 90,0%, and 88.9%, respectively. The area under the ROC curve was 96.7% (95% confidence interval 89.7–100.0%). Conclusion: This proof of principle study is a first step in the development of an SFR spectroscopy technique to detect LN metastases in real time. A next step towards this goal is replicating these results in LNs with smaller metastases and in a larger cohort of patients. This future study will combine SFR spectroscopy with fine-needle aspiration, using the same needle, to perform preoperative in vivo measurements.</p

A functional genomic perspective on human well-being

To identify molecular mechanisms underlying the prospective health advantages associated with psychological well-being, we analyzed leukocyte basal gene expression profiles in 80 healthy adults who were assessed for hedonic and eudaimonic well-being, as well as potentially confounded negative psychological and behavioral factors. Hedonic and eudaimonic well-being showed similar affective correlates but highly divergent transcriptome profiles. Peripheral blood mononuclear cells from people with high levels of hedonic well-being showed up-regulated expression of a stress-related conserved transcriptional response to adversity (CTRA) involving increased expression of proinflammatory genes and decreased expression of genes involved in antibody synthesis and type I IFN response. In contrast, high levels of eudaimonic well-being were associated with CTRA down-regulation. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity in structuring the observed differences in gene expression associated with eudaimonic well-being (reduced NF-κB and AP-1 signaling and increased IRF and STAT signaling). Transcript origin analysis identified monocytes, plasmacytoid dendritic cells, and B lymphocytes as primary cellular mediators of these dynamics. The finding that hedonic and eudaimonic well-being engage distinct gene regulatory programs despite their similar effects on total well-being and depressive symptoms implies that the human genome may be more sensitive to qualitative variations in well-being than are our conscious affective experiences

Neural Basis of Moral Elevation Demonstrated through Inter-Subject Synchronization of Cortical Activity during Free-Viewing

Most research investigating the neural basis of social emotions has examined emotions that give rise to negative evaluations of others (e.g. anger, disgust). Emotions triggered by the virtues and excellences of others have been largely ignored. Using fMRI, we investigated the neural basis of two "other-praising" emotions--Moral Elevation (a response to witnessing acts of moral beauty), and Admiration (which we restricted to admiration for physical skill).Ten participants viewed the same nine video clips. Three clips elicited moral elevation, three elicited admiration, and three were emotionally neutral. We then performed pair-wise voxel-by-voxel correlations of the BOLD signal between individuals for each video clip and a separate resting-state run. We observed a high degree of inter-subject synchronization, regardless of stimulus type, across several brain regions during free-viewing of videos. Videos in the elevation condition evoked significant inter-subject synchronization in brain regions previously implicated in self-referential and interoceptive processes, including the medial prefrontal cortex, precuneus, and insula. The degree of synchronization was highly variable over the course of the videos, with the strongest synchrony occurring during portions of the videos that were independently rated as most emotionally arousing. Synchrony in these same brain regions was not consistently observed during the admiration videos, and was absent for the neutral videos.Results suggest that the neural systems supporting moral elevation are remarkably consistent across subjects viewing the same emotional content. We demonstrate that model-free techniques such as inter-subject synchronization may be a useful tool for studying complex, context dependent emotions such as self-transcendent emotion

Prognostication using SpO(2)/FiO(2) in invasively ventilated ICU patients with ARDS due to COVID-19-Insights from the PRoVENT-COVID study

Background: The SpO(2)/FiO(2) is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO(2)/FiO(2) for mortality in patients with ARDS due to COVID-19. Methods: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. Results: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO(2)/FiO(2) on day 1 had no prognostic value. The SpO(2)/FiO(2) on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO(2)/FiO(2) on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO(2) and the PaO2/FiO(2) calculated from SpO(2)/FiO(2) were strongly correlated (Spearman's r = 0.79). Conclusions: In this cohort of patients with ARDS due to COVID-19, the SpO(2)/FiO(2) on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO(2)/FiO(2) is a useful metric for risk stratification in invasively ventilated COVID-19 patients. (C) 2021 The Authors. Published by Elsevier Inc

Listening in the dark: why we need stories of people living with severe and enduring anorexia nervosa

A bold step forward in our approach to Severe and Enduring Anorexia Nervosa invites new paradigms for research and practice. It provides an opportunity for us to explore fault lines, both in our communities of practice and the social structures that inform them. This paper serves to question the medical metaphors on which treatment has been based, in favour of alternative perspectives that resonate more clearly with the lived experience of those for whom it has failed. We invite the consideration of alternative metaphors, which can disrupt the notion of heroic patients (and therapists), mediate against acts of self-silencing and sensitising us to more radical acts of listening. Beyond the randomised trials and manuals it is time for us to listen to the realities of suffering, the minutiae of resistance and the life that can still be lived

Gaps in Capacity in Primary Care in Low-Resource Settings for Implementation of Essential Noncommunicable Disease Interventions

Objective. The objective was to evaluate the capacity of primary care (PC) facilities to implement basic interventions for prevention and management of major noncommunicable diseases (NCDs), including cardiovascular diseases and diabetes. Methods. A cross-sectional survey was done in eight low- and middle-income countries (Benin, Bhutan, Eritrea, Sri Lanka, Sudan, Suriname, Syria, and Vietnam) in 90 PC facilities randomly selected. The survey included questions on the availability of human resources, equipment, infrastructure, medicines, utilization of services, financing, medical information, and referral systems. Results and Conclusions. Major deficits were identified in health financing, access to basic technologies and medicines, medical information systems, and the health workforce. The study has provided the foundation for strengthening PC to address noncommunicable diseases. There are important implications of the findings of this study for all low- and middle-income countries as capacity of PC is fundamental for equitable prevention and control of NCDs

Conflicted Emotions Following Trust-based Interaction

We investigated whether 20 emotional states, reported by 170 participants after participating in a Trust game, were experienced in a patterned way predicted by the “Recalibrational Model” or Valence Models. According to the Recalibrational Model, new information about trust-based interaction outcomes triggers specific sets of emotions. Unlike Valence Models that predict reports of large sets of either positive or negative emotional states, the Recalibrational Model predicts the possibility of conflicted (concurrent positive and negative) emotional states. Consistent with the Recalibrational Model, we observed reports of conflicted emotional states activated after interactions where trust was demonstrated but trustworthiness was not. We discuss the implications of having conflicted goals and conflicted emotional states for both scientific and well-being pursuits

Postpartum psychiatric disorders

Pregnancy is a complex and vulnerable period that presents a number of challenges to women, including the development of postpartum psychiatric disorders (PPDs). These disorders can include postpartum depression and anxiety, which are relatively common, and the rare but more severe postpartum psychosis. In addition, other PPDs can include obsessive–compulsive disorder, post-traumatic stress disorder and eating disorders. The aetiology of PPDs is a complex interaction of psychological, social and biological factors, in addition to genetic and environmental factors. The goals of treating postpartum mental illness are reducing maternal symptoms and supporting maternal–child and family functioning. Women and their families should receive psychoeducation about the illness, including evidence-based discussions about the risks and benefits of each treatment option. Developing effective strategies in global settings that allow the delivery of targeted therapies to women with different clinical phenotypes and severities of PPDs is essential