Dynamic tracking of microvascular hemoglobin content for continuous perfusion monitoring in the intensive care unit: pilot feasibility study

Purpose: There is a need for bedside methods to monitor oxygen delivery in the microcirculation. Near-infrared spectroscopy commonly measures tissue oxygen saturation, but does not reflect the time-dependent variability of microvascular hemoglobin content (MHC) that attempts to match oxygen supply with demand. The objective of this study is to determine the feasibility of MHC monitoring in critically ill patients using high-resolution near-infrared spectroscopy to assess perfusion in the peripheral microcirculation. Methods: Prospective observational cohort of 36 patients admitted within 48 h at a tertiary intensive care unit. Perfusion was measured on the quadriceps, biceps, and/or deltoid, using the temporal change in optical density at the isosbestic wavelength of hemoglobin (798 nm). Continuous wavelet transform was applied to the hemoglobin signal to delineate frequency ranges corresponding to physiological oscillations in the cardiovascular system. Results: 31/36 patients had adequate signal quality for analysis, most commonly affected by motion artifacts. MHC signal demonstrates inter-subject heterogeneity in the cohort, indicated by different patterns of variability and frequency composition. Signal characteristics were concordant between muscle groups in the same patient, and correlated with systemic hemoglobin levels and oxygen saturation. Signal power was lower for patients receiving vasopressors, but not correlated with mean arterial pressure. Mechanical ventilation directly impacts MHC in peripheral tissue. Conclusion: MHC can be measured continuously in the ICU with high-resolution near-infrared spectroscopy, and reflects the dynamic variability of hemoglobin distribution in the microcirculation. Results suggest this novel hemodynamic metric should be further evaluated for diagnosing microvascular dysfunction and monitoring peripheral perfusion

Psychological approaches to understanding and promoting recovery in psychosis and bipolar disorder:a mixed-methods approach

BackgroundRecovery in mental health is a relatively new concept, but it is becoming more accepted that people can recover from psychosis. Recovery-orientated services are recommended for adult mental health, but with little evidence base to support this. ObjectivesTo facilitate understanding and promotion of recovery in psychosis and bipolar disorder (BD), in a manner that is empowering and acceptable to service users. MethodThere were six linked projects using qualitative and quantitative methodologies: (1) developing and piloting a service user-defined measure of recovery; (2) a Delphi study to determine levels of consensus around the concept of recovery; (3) examination of the psychological factors associated with recovery and how these fluctuate over time; (4) development and evaluation of cognitive–behavioural approaches to guided self-help including a patient preference trial (PPT); (5) development and evaluation of cognitive–behavioural therapy (CBT) for understanding and preventing suicide in psychosis including a randomised controlled trial (RCT); and (6) development and evaluation of a cognitive–behavioural approach to recovery in recent onset BD, including a RCT of recovery-focused cognitive–behavioural therapy (RfCBT). Service user involvement was central to the programme. ResultsMeasurement of service user-defined recovery from psychosis (using the Subjective Experience of Psychosis Scale) and BD (using the Bipolar Recovery Questionnaire) was shown to be feasible and valid. The consensus study revealed a high level of agreement among service users for defining recovery, factors that help or hinder recovery and items which demonstrate recovery. Negative emotions, self-esteem and hope predicted recovery judgements, both cross-sectionally and longitudinally, whereas positive symptoms had an indirect effect. In the PPT, 89 participants entered the study, three were randomised, 57 were retained in the trial until 15-month follow-up (64%). At follow-up there was no overall treatment effect on the primary outcome (Questionnaire about the Process of Recovery total; p = 0.82). In the suicide prevention RCT, 49 were randomised and 35 were retained at 6-month follow-up (71%). There were significant improvements in suicidal ideation [Adult Suicidal Ideation Questionnaire; treatment effect = –12.3, 95% confidence interval (CI) –24.3 to –0.14], Suicide Probability Scale (SPS; treatment effect = –7.0, 95% CI –15.5 to 0) and hopelessness (subscale of the SPS; treatment effect = –3.8, 95% CI –7.3 to –0.5) at follow-up. In the RCT for BD, 67 participants were randomised and 45 were retained at the 12-month follow-up (67%). Recovery score significantly improved in comparison with treatment as usual (TAU) at follow-up (310.87, 95% CI 75.00 to 546.74). At 15-month follow-up, 32 participants had experienced a relapse of either depression or mania (20 TAU vs. 12 RfCBT). The difference in time to recurrence was significant (estimated hazard ratio 0.38, 95% CI 0.18 to 0.78; p < 0.006). ConclusionsThis research programme has improved our understanding of recovery in psychosis and BD. Key findings indicate that measurement of recovery is feasible and valid. It would be feasible to scale up the RCTs to assess effectiveness of our therapeutic approaches in larger full trials, and two of the studies (CBT for suicide prevention in psychosis and recovery in BD) found significant benefits on their primary outcomes despite limited statistical power, suggesting definitive trials are warranted. FundingThe National Institute for Health Research Programme Grants for Applied Research programme

Ngā Whakāwhitinga (standing at the crossroads): How Māori understand what Western psychiatry calls “schizophrenia”

This project explored how Māori understand experiences commonly labelled “schizophrenic” or “psychotic”. Semi-structured interviews were conducted with 57 Māori participants who had either personal experiences labelled as “psychosis” or “schizophrenia”, or who work with people with such experiences; including tangata whaiora (users of mental health services), tohunga (traditional healers), kaumatua/kuia (elders), Māori clinicians, cultural support workers and students. Kaupapa Māori Theory and Personal Construct Theory guided the research within a qualitative methodology. The research found that participants held multiple explanatory models for experiences commonly labelled “psychotic” or “schizophrenic”. The predominant explanations were spiritual and cultural. It seems that cultural beliefs and practices related to mental health within Māori communities remain resilient, despite over a century of contact with mainstream education and health services. Other explanations included psychosocial constructions (interpersonal trauma and drug abuse), historical trauma (colonisation) and biomedical constructions (chemical brain imbalance). Participants (both tangata whaiora and health professionals) reported they were apprehensive about sharing their spiritual/cultural constructions within mainstream mental health settings due to fear of being ignored or pathologised. This study highlights the importance of asking users of mental health services about the meaning they place on their experiences and recognising that individuals can hold multiple explanatory models. Māori may hold both Māori and Pākehā (European) ways of understanding their experiences and meaningful recognition should be afforded to both throughout assessment and treatment planning in mental health services. Clinicians need to be aware that important personal and cultural meanings of experiences labelled psychotic may be withheld due to fear of judgement or stigmatisation

Annexin A5 in Patients With Severe COVID-19 Disease: A Single-Center, Randomized, Double-Blind, Placebo-Controlled Feasibility Trial

OBJECTIVES:. To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19). DESIGN:. Double-blind, randomized clinical trial. SETTING:. Two ICUs at an academic medical center. PATIENTS/SUBJECTS:. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support. INTERVENTIONS:. SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days. MEASUREMENTS AND MAIN RESULTS:. We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial. LIMITATIONS:. The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial. CONCLUSIONS:. Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis

Detection and Profiling of Human Coronavirus Immunoglobulins in Critically Ill Coronavirus Disease 2019 Patients

Objectives:. Coronavirus disease 2019 continues to spread worldwide with high levels of morbidity and mortality. We performed anticoronavirus immunoglobulin G profiling of critically ill coronavirus disease 2019 patients to better define their underlying humoral response. Design:. Blood was collected at predetermined ICU days to measure immunoglobulin G with a research multiplex assay against four severe acute respiratory syndrome coronavirus 2 proteins/subunits and against all six additionally known human coronaviruses. Setting:. Tertiary care ICU and academic laboratory. Subjects:. ICU patients suspected of being infected with severe acute respiratory syndrome coronavirus 2 had blood collected until either polymerase chain reaction testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until death or discharge if the patient tested polymerase chain reaction positive (coronavirus disease 2019 positive). Interventions:. None MEASUREMENTS AND MAIN RESULTS:. Age- and sex-matched healthy controls and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients had greater body mass indexes, presented with bilateral pneumonias more frequently, and suffered lower Pao2:Fio2 ratios, when compared with coronavirus disease 2019 negative patients (p < 0.05). Mortality rate for coronavirus disease 2019 positive patients was 50%. On ICU days 1–3, anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G was significantly elevated in coronavirus disease 2019 positive patients, as compared to both healthy control subjects and coronavirus disease 2019 negative patients (p < 0.001). Weak severe acute respiratory syndrome coronavirus immunoglobulin G serologic responses were also detected, but not other coronavirus subtypes. The four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G were maximal by ICU day 3, with all four anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G providing excellent diagnostic potential (severe acute respiratory syndrome coronavirus 2 Spike 1 protein immunoglobulin G, area under the curve 1.0, p < 0.0005; severe acute respiratory syndrome coronavirus receptor binding domain immunoglobulin G, area under the curve, 0.93–1.0; p ≤ 0.0001; severe acute respiratory syndrome coronavirus 2 Spike proteins immunoglobulin G, area under the curve, 1.0; p < 0.0001; severe acute respiratory syndrome coronavirus 2 Nucleocapsid protein immunoglobulin G area under the curve, 0.90–0.95; p ≤ 0.0003). Anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G increased and/or plateaued over 10 ICU days. Conclusions:. Critically ill coronavirus disease 2019 patients exhibited anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G, whereas serologic responses to non–severe acute respiratory syndrome coronavirus 2 antigens were weak or absent. Detection of human coronavirus immunoglobulin G against the different immunogenic structural proteins/subunits with multiplex assays may be useful for pathogen identification, patient cohorting, and guiding convalescent plasma therapy