Characterization of the Inflammatory Response to Severe COVID-19 Illness.

Rationale: Coronavirus disease (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood.Objectives: To define the cytokine profile of COVID-19 and to identify evidence of immunometabolic alterations in those with severe illness.Methods: Levels of IL-1ß, IL-6, IL-8, IL-10, and sTNFR1 (soluble tumor necrosis factor receptor 1) were assessed in plasma from healthy volunteers, hospitalized but stable patients with COVID-19 (COVIDstable patients), patients with COVID-19 requiring ICU admission (COVIDICU patients), and patients with severe community-acquired pneumonia requiring ICU support (CAPICU patients). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of AAT (alpha-1 antitrypsin) to COVID-19 was also evaluated.Measurements and Main Results: IL-1ß, IL-6, IL-8, and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable patients, and demonstrated higher levels of IL-1ß, IL-6, and sTNFR1 but lower IL-10 than CAPICU patients. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2 (pyruvate kinase M2), phosphorylated PKM2, HIF-1α (hypoxia-inducible factor-1α), and lactate. The production and sialylation of AAT increased in COVID-19, but this antiinflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P < 0.0001). In critically unwell patients with COVID-19, increases in IL-6:AAT predicted prolonged ICU stay and mortality, whereas improvement in IL-6:AAT was associated with clinical resolution (P < 0.0001).Conclusions: The COVID-19 cytokinemia is distinct from that of other types of pneumonia, leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population.

Income loss and the mental health of young mothers: evidence from the recession in Ireland.

BACKGROUND: There are many potential pathways in the income health relationship. Problems arise in examining the effect of income loss primarily because of difficulties in disentangling income from the effect of the labour market, but also because of the heterogenous nature of health variables. Psychological, rather than physical, health is important because younger populations are unlikely to manifest clinical evidence of physical disease in the short term. However, biological pathways of stress indicate that this can result in increased mortality and morbidity in the longer term. AIMS OF THE STUDY: The study follows the example of work that has harnessed the Great Recession to examine income loss, but in contrast to previous work, this study examines the relationship of disposable income and mental health. The study exploits disposable, rather than gross, income, because of economic theory relating disposable income to consumption and research demonstrating the role of consumption in wellbeing. Data from the period of the Great Recession in Ireland allows the examination of changes in disposable income due to government policies that reduced public expenditure and increased taxation. METHODS: Using three waves of panel data from the Growing Up in Ireland study a fixed effects approach is taken to examine disposable income and the mental health of the mothers of young children. A balanced panel is used which results in 6821 individuals being studied over the three waves. The primary dependent variable of interest is depression, scored using a short form of the Centre for Epidemiological Depression Scale (CES-D), although additional outcomes of interest include treatment for a mental health condition, and measures of parental stress using the Parental Stress Scale. RESULTS: There is a statistically significant relationship between changes in depression score and disposable income loss over the three waves. This relationship is independent of labour market loss during that time. The effect of income loss is predominantly seen for those who are homeowners. Subjective reports of being in mortgage or rent arrears are also associated with an increase in depression score. DISCUSSION: This group, comprising the mothers of young children, is particularly interesting in view of the credit constraints experienced by younger households during the financial crisis in Ireland. Both sets of results are consistent with qualitative studies which have shown that mortgage difficulties can lead to depression, anxiety and poor mental health, and that high status groups experience shame and self-blame when they experience a financial loss. It remains to be seen if this will have a long-term effect on the mental health of either the mothers or their children.

Recovery of a critically ill patient with COVID-19 myocarditis.

Myocarditis is a concerning potential consequence of COVID-19 infection, attributed to ventricular dysfunction, cardiac fibrosis, ventricular arrhythmias, cardiogenic shock, and sudden cardiac death. Recently, the Israeli Health Ministry announced that a small number of cases of myocarditis may be linked to second dose of Pfizer's BioNTech-partnered COVID-19 vaccine. The long-term impact of COVID-19 myocarditis and coronary microthrombosis which has also been described and the best therapies for these complications remain unknown. Indeed, monomorphic ventricular tachycardia and regular ventricular arrhythmias have previously been found to be more common in those recovered from myocarditis than in acute myocarditis itself. Follow-up assessment of cardiac function has been suggested for this cohort to detect and possibly prevent further cardiac events in the rehabilitation phase. Functional capacity has been shown to be a better determinant of long-term morbidity than diagnostic testing alone, but integrated approach is likely the way forward in clinical follow-up. Assessment of residual complications in the post-COVID-19 recovery phase may identify the population burden of long-term cardiac disease as a direct consequence of COVID-19.

Complex rectal polyps: other treatment modalities required when offering a transanal endoscopic microsurgery service.

PURPOSE: Complex rectal polyps may present a clinical challenge. The study aim was to assess different treatment modalities required in the management of patients referred for transanal endoscopic microsurgery. METHODS: Patients referred with complex rectal polyps from 1998 to 2008 were entered prospectively to a colorectal database. These data was analyzed for referral pattern, histology, surgical procedures performed, and subsequent outcome. RESULTS: Of the 209 patients referred (101 female, 108 male, median age of 65 years, range of 24-89), 132 (63%) were deemed suitable for transanal endoscopic microsurgery. Seventeen patients required a second staged procedure; three patients required an anterior resection at time of index surgery. Seventeen patients referred for transanal endoscopic microsurgery went direct to anterior resection, 37 underwent snare polypectomy (SP), and 17 patients underwent transanal excision. Six patients had no surgery (three unfit for anesthesia and three had no residual lesions). Thus, 37% of the patients referred for transanal endoscopic microsurgery required a different treatment modality. CONCLUSIONS: Majority of patients referred to our unit with complex rectal polyps were suitable for transanal endoscopic microsurgery. However, this study highlights that in offering a transanal microsurgery service, one should be prepared for a diversity of pathology necessitating a range of management options.

An integrated multidisciplinary model of COVID-19 recovery care.

BACKGROUND: In January 2020, the WHO declared the SARS-CoV-2 outbreak a public health emergency; by March 11, a pandemic was declared. To date in Ireland, over 3300 patients have been admitted to acute hospitals as a result of infection with COVID-19. AIMS: This article aims to describe the establishment of a COVID Recovery Service, a multidisciplinary service for comprehensive follow-up of patients with a hospital diagnosis of COVID-19 pneumonia. METHODS: A hybrid model of virtual and in-person clinics was established, supported by a multidisciplinary team consisting of respiratory, critical care, infectious diseases, psychiatry, and psychology services. This model identifies patients who need enhanced follow-up following COVID-19 pneumonia and aims to support patients with complications of COVID-19 and those who require integrated community care. RESULTS: We describe a post-COVID-19 service structure together with detailed protocols for multidisciplinary follow-up. One hundred seventy-four patients were discharged from Beaumont Hospital after COVID-19 pneumonia. Sixty-seven percent were male with a median age (IQR) of 66.5 (51-97). Twenty-two percent were admitted to the ICU for mechanical ventilation, 11% had non-invasive ventilation or high flow oxygen, and 67% did not have specialist respiratory support. Early data suggests that 48% of these patients will require medium to long-term specialist follow-up. CONCLUSIONS: We demonstrate the implementation of an integrated multidisciplinary approach to patients with COVID-19, identifying those with increased physical and mental healthcare needs. Our initial experience suggests that significant physical, psychological, and cognitive impairments may persist despite clinical resolution of the infection.

Factors that influence family and parental preferences and decision making for unscheduled paediatric healthcare: a systematic review protocol.

There is a plethora of factors that dictate where parents and families choose to seek unscheduled healthcare for their child; and the complexity of these decisions can present a challenge for policy makers and healthcare planners as these behaviours can have a significant impact on resources in the health system. The systematic review will seek to identify the factors that influence parents' and families' preferences and decision making when seeking unscheduled paediatric healthcare.  Five databases will be searched for published studies (CINAHL, PubMed, SCOPUS, PsycInfo, EconLit) and grey literature will also be searched. Inclusion and exclusion criteria will be applied and articles assessed for quality. A narrative approach will be used to synthesise the evidence that emerges from the review. By collating the factors that influence decision-making and attendance at these services, the review can inform future health policies and strategies seeking to expand primary care to support the provision of accessible and responsive care. The systematic review will also inform the design of a discrete choice experiment (DCE) which will seek to determine parental and family preferences for unscheduled paediatric healthcare. Policies such as Sláintecare that seek to expand primary care and reduce hospital admissions from emergency departments need to be cognisant of the nuanced and complex factors that govern patients' behaviour.