Using Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors in Critical Care: A Systematic Review of the Evidence for Benefit or Harm.

OBJECTIVE: Selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors are among the most commonly prescribed drugs in patients admitted to the ICU. Our objective was to systematically review available literature for evidence of benefit or harm in ICU patients resulting from chronic effects, continued use, or withdrawal. DATA SOURCES: Medline, Embase, and Cochrane Central Register of Controlled Trials (1990 to November 2014). STUDY SELECTION: We searched for studies of ICU patients with recorded selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor prescription before or during admission, and reporting morbidity, mortality, adverse events, and resource measures like ICU length of stay. We considered all study designs. We excluded studies of deliberate overdose and depression in non-ICU settings. Two authors independently and in duplicate screened citations and reviewed text of studies to apply selection criteria. DATA EXTRACTION: Two authors abstracted data on patient characteristics in exposed and control groups; use of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors previously or during ICU; comparator intervention; and outcomes, and also assessed methodologic quality. DATA SYNTHESIS: The database search retrieved 4,172 unique citations, of which 289 were reviewed, and 13 studies representing a total of 20,048 patients met selection criteria. There were five cohort studies, one case series, and seven case reports. Only one case report suggested benefit from selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor use and 11 studies reported morbidity in patients using these medications at admission to ICU. However, due to inadequate drug administration reporting, it was generally unclear if outpatient selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors were continued in ICU, complicating interpretation. CONCLUSIONS: There may be excess morbidity in critically ill selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor users, but uncertainty remains whether this is due to chronic effects, ongoing use, or drug withdrawal. Further research with improved standards of drug administration reporting is needed to help clinicians decide when to use selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitors in critically ill patients.

Shrink rethink: rebranding psychiatry.

Negative public attitudes towards psychiatry hinder individuals coming for treatment and prevent us from attracting and retaining the very brightest and best doctors. As psychiatrists we are skilled in using science to change the thoughts and behaviours of individuals, however, we lack the skills to engage entire populations. Expertise in this field is the preserve of branding, advertising and marketing professionals. Techniques from these fields can be used to rebrand psychiatry at a variety of levels from national recruitment drives to individual clinical interactions between psychiatrists and their patients.

Choice of antipsychotic treatment by European psychiatry trainees: are decisions based on evidence?

BACKGROUND: Little is known about the factors influencing treatment choice in psychosis, the majority of this work being conducted with specialists (consultant) in psychiatry. We sought to examine trainees' choices of treatment for psychosis if they had to prescribe it for themselves, their patients, and factors influencing decision-making. METHODS: Cross-sectional, semi-structured questionnaire-based study. RESULTS: Of the 726 respondents (response rate = 66%), the majority chose second-generation antipsychotics (SGAs) if they had to prescribe it for themselves (n = 530, 93%) or for their patients (n = 546, 94%). The main factor influencing choice was perceived efficacy, 84.8% (n = 475) of trainees stating this was the most important factor for the patient, and 77.8% (n = 404) stating this was the most important factor for their own treatment. Trainees with knowledge of trials questioning use of SGAs (CATIE, CUtLASS, TEOSS) were more likely to choose second-generation antipsychotics than those without knowledge of these trials (χ2 = 3.943; p = 0.047; O.R. = 2.11; 95% C.I. = 1.0-4.48). Regarding psychotherapy, cognitive behavioural therapy (CBT) was the most popular choice for self (33.1%; n = 240) and patient (30.9%; n = 224). Trainees were significantly more likely to prefer some form of psychotherapy for themselves rather than patients (χ2 = 9.98; p < 0,002; O.R. = 1.54; 95% CIs = 1.18-2.0). CONCLUSIONS: Trainees are more likely to choose second-generation antipsychotic medication for patients and themselves. Despite being aware of evidence that suggests otherwise, they predominantly base these choices on perceived efficacy.

Attitudes towards mental illness in Malawi: a cross-sectional survey.

BACKGROUND: Stigma and discrimination associated with mental illness are strongly linked to suffering, disability and poverty. In order to protect the rights of those with mental disorders and to sensitively develop services, it is vital to gain a more accurate understanding of the frequency and nature of stigma against people with mental illness. Little research about this issue has been conducted in Sub- Saharan Africa. Our study aimed to describe levels of stigma in Malawi. METHODS: A cross-sectional survey of patients and carers attending mental health and non-mental health related clinics in a general hospital in Blantyre, Malawi. Participants were interviewed using an adapted version of the questionnaire developed for the "World Psychiatric Association Program to Reduce Stigma and Discrimination Because of Schizophrenia". RESULTS: 210 participants participated in our study. Most attributed mental disorder to alcohol and illicit drug abuse (95.7%). This was closely followed by brain disease (92.8%), spirit possession (82.8%) and psychological trauma (76.1%). There were some associations found between demographic variables and single question responses, however no consistent trends were observed in stigmatising beliefs. These results should be interpreted with caution and in the context of existing research. Contrary to the international literature, having direct personal experience of mental illness seemed to have no positive effect on stigmatising beliefs in our sample. CONCLUSIONS: Our study contributes to an emerging picture that individuals in Sub-Saharan Africa most commonly attribute mental illness to alcohol/ illicit drug use and spirit possession. Our work adds weight to the argument that stigma towards mental illness is an important global health and human rights issue.

18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome.

BACKGROUND: Acute aortic syndrome is associated with aortic medial degeneration. 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity. OBJECTIVES: In a proof-of-concept study, this investigation aimed to establish whether 18F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome. METHODS: Patients with aortic dissection or intramural hematomas and control subjects underwent 18F-NaF PET/CT angiography of the aorta. Aortic 18F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBRmax]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months. RESULTS: Aortic 18F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased 18F-NaF uptake (TBRmax: 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). 18F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019). CONCLUSIONS: In patients with acute aortic syndrome, 18F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. 18F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. (18F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566).

Progenitor cell characterization and location in the developing human liver.

Tissue-derived stem cells may offer future liver disease therapies. The developing human liver provides an excellent model to examine normal hepatic progenitor cell maturation, but candidate populations are poorly characterized. We sought to identify putative progenitor phenotypes in first-trimester human liver, by characterizing the architectural relationship between developing epithelial, mesenchymal, and hematopoietic lineages. Bipotential hepatoblasts were identified by co-expression of hepatocytic (cytokeratin 18, albumin) and biliary(cytokeratin 19) specific markers and epithelial-specific E-cadherin. Restriction of dlk/pref-1 expression to hepatoblasts identifies this as a novel human marker allowing for hepatoblast sorting for in vitro analysis. Furthermore, the liver stem cell and haematopoietic marker Thy-1 was co-expressed with markers of hematopoietic (CD34) and mesenchymal (vimentin) lineage restriction on portal vein endothelium. Therefore, this structure may constitute a novel progenitor compartment with hemangioblast-like properties.

The Endovascular Preprocedural Run Through and Brief: A Simple Intervention to Reduce Radiation Dose and Contrast Load in Endovascular Aneurysm Repair.

OBJECTIVES: To assess the impact of a quality assured planning and sizing process and the endovascular team briefing (preprocedure run through and brief - PRTB) on the delivery of endovascular aneurysm repair (EVAR), in Edinburgh. DESIGN: Prospective observational study, comparing parameters before and after the intervention. MATERIALS: Prospectively collected database recording infrarenal aneurysms treated with EVAR performed from January 2007 to April 2014 at our institution. The total screening time, iodinated contrast volume used, radiation dose, endovascular training opportunities, and hospital length of stay were recorded. METHODS: A comparison before (January 2007 to November 2011) and after (December 2011 to April 2014) the introduction of the PRTB was made for each of these variables. Multiple linear regression analysis was performed to account for the learning effect. RESULTS: In this study, 61 EVAR cases were performed prior to and 44 EVAR cases after the introduction of the PRTB. Univariate Mann-Whitney tests suggested a significant difference between before PRTB introduction and after PRTB introduction on all outcome variables except procedure time. Multiple linear regression analysis results showed a statistically significant improvement in outcomes after the change point for all outcomes except for radiation dose. Endovascular training opportunities were realized in 12/61 (20%) before compared to 42/44 cases (95%) after PRTB introduction. CONCLUSIONS: By introducing rigorous quality assurance and utilizing the principles of crew resource management to the EVAR process, it is possible to reduce screening times, contrast use, hospital length of stay, and improve endovascular training opportunities.

X inactivation patterns of closely, but not distantly, related cells are highly correlated: little evidence for stem cell plasticity in normal females.

The early, random nature of X inactivation should cause related cells to have similar, but distinctive, active X chromosomes. We assessed the frequency of stem cell plasticity using X inactivation proportions (XIPs), determined at the human androgen receptor locus, in paired tissue samples from healthy individuals. Tissues sampled were stomach (n = 18 informative females), duodenum (n = 18), colon (n = 10) with corresponding peripheral blood samples (n = 33), and varicose veins (n = 28) with corresponding T cells (n = 26) and peripheral blood granulocytes (n = 25). XIPs from samples thought to have common stem cell origins were highly correlated: multiple samples from single vein, r = .80 (n = 24); T cells versus granulocytes, r = .67 (n = 23); duodenum versus stomach, r = .63 (n = 12). Blood cells and vessels are derived from a common hemangioblast, but XIP correlations were moderate or poor: vein versus T cells, r = .42 (n = 26); vein versus granulocytes, r = .11 (n = 25). X inactivation is believed to be a late process in gut, especially hind-gut, with corresponding independence from blood precursors. Correlations with blood cells were low: stomach, r = .23 (18); duodenum, r = .21 (18); colon, r = .034 (10). Any crossover of stem cells between different organs during adult life should increase correlations with age; no such increase was seen. This study confirms that XIPs can be used to track stem cell populations, provides a theoretical basis for the power of such studies, and indicates that hemopoietic stem cell plasticity is, at most, uncommon in normal humans.

Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1.

Hepatic progenitor cells play a major role in regenerating diseased liver. In rodents, progenitors forming hepatocytes or cholangiocytes are identified by the stem cell marker Thy-1. The aim of this study was to ascertain whether progenitor cells expressing Thy-1 could be identified in human fetal liver. Midtrimester human fetal liver was immunostained for Thy-1, cytokeratins 18 and 19, vimentin, CD34, CD45, and fibrinogen. Thy-1+ and Thy-1+CD34+ populations were purified using fluorescence-activated cell sorting (FACS). Immunofluorescence and mRNA expression were used to examine the bipotential nature of purified stem cells. We found that Thy-1+ cells were concentrated in portal tracts but were also scattered in parenchyma. In FACS-prepared cells, 0.18-3.08% (median 0.65%, n = 14) of cells were Thy-1+. Immunophenotyping revealed that some Thy-1+ cells coexpressed cytokeratins 18 and 19, others, fibrinogen and cytokeratin 19. RT-PCR demonstrated that Thy-1+ cells expressed mRNA for Thy-1, cytokeratin 18, and cytokeratin 19, and Thy-1+CD34+ cells expressed mRNA for alpha-fetoprotein, transferrin, and hepatocyte nuclear factor-4alpha. Thy-1+ cells were identified in fetal liver. These cells expressed several lineage markers, including coexpression of biliary and hepatocellular proteins and mRNA. These data suggest that Thy-1 is a marker of liver stem cells in human fetal liver.

The attitudes of medical students towards homeless people: does medical school make a difference?

BACKGROUND: Homeless people have greater health care needs than those who are housed, yet often experience difficulty in accessing health care. Evidence suggests that the attitudes of doctors can create significant barriers to health care for homeless people. METHODS: A validated structured questionnaire, the Attitudes Towards the Homeless Questionnaire (ATHQ), was posted to a year group of 211 medical students 2 weeks prior to their starting at the University of Birmingham in 1997, and again during their final clinical placement 5 years later. The results were explored in more depth through semistructured interviews with the 12 students displaying the greatest degree of attitude change. RESULTS: The response rates for the 1997 and 2002 surveys were 80% and 82%, respectively, with an overall response rate of 65% of eligible students. The mean ATHQ scores for the 2 time periods were 76.3 and 74.7 (mean difference = 1.66 +/- 0.8, paired t test = 2.07, P = 0.04), indicating that attitudes had become more negative during the 5-year period. Semistructured interviews highlighted the importance of professional socialisation and clinical contact on attitude development. CONCLUSION: This study suggests that medical students may hold more negative attitudes towards homeless people at the end of their undergraduate course than they do at the beginning of it. Medical schools may need to address this area of health care more directly in the undergraduate curriculum if tomorrow's doctors are to treat all patients equally.