Mortality prediction upon hospital admission – the value of clinical assessment: A retrospective,matched cohort study

Accurate prediction of mortality upon hospital admission is of great value, both for the sake of patients and appropriate resources’ allocation. A myriad of assessment tools exists for this purpose. The evidence relating to the comparative value of clinical assessment versus established indexes are scarce. We analyzed the accuracy of a senior physician’s clinical assessment in a retrospective cohort of patients in a crude, general patients’ population and later on a propensity matched patients’ population. In one department of internal medicine in a tertiary hospital, of 9891 admitted patients, 973 (10%) were categorized as prone to death in a 6-months’ duration by a senior physician. The risk of death was significantly higher for these patients [73.1% vs 14.1% mortality within 180 days; hazard ratio (HR) = 7.58; confidence intervals (CI) 7.02‐8.19, P < .001]. After accounting for multiple, other patients’ variables associated with increased risk of mortality, the correlation remained significant (HR = 3.25; CI 2.85‐3.71, P < .001). We further performed a propensity matching analysis (a subgroup of 710 patients, subdivided to two groups with 355 patients each): survival rates were as low as 45% for patients categorized as prone to death compared to 78% in patients who weren’t categorized as such (P < .001). Reliance on clinical evaluation, done by an experienced senior physician, is an appropriate tool for mortality prediction upon hospital admission, achieving high accuracy rates.     

An open-label study of amisulpride in the treatment of mania

BACKGROUND: Amisulpride is a selective D(2)-D(3) antagonist that has been reported to be effective in the treatment of schizophrenia and major depressive disorder. However, no prospective study to date has assessed the effectiveness and tolerability of this compound in mania. METHOD: Twenty DSM-IV-defined acutely ill manic bipolar patients with a Young Mania Rating Scale (YMRS) score of 20 or more entered this open, prospective, 6-week study. Assessments included the YMRS, the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions Scale for Bipolar Disorder, Modified (CGI-BP-M), and the systematic report of adverse events. Amisulpride was added to other medications, but other antipsychotics were not allowed. RESULTS: Fourteen patients (70%) completed the study. Using last-observation-carried-forward (LOCF) analyses, amisulpride produced significant improvements on the YMRS (p = .0001), the HAM-D (p < .0141), and the overall (p = .0003), mania (p = .0001), and depression (p = .0268) subscales of the CGI-BP-M. The most common side effect was sedation (N = 5, 25%), but there were also some extrapyramidal symptoms, galactorrhea, insomnia, and agitation. The mean amisulpride dose was 680 mg/day (LOCF) and 786 mg/day in completers. CONCLUSIONS: This first prospective study on amisulpride in the treatment of mania suggests that, despite the limitations of the open, observational design and small sample size, amisulpride may be effective and reasonably safe in the treatment of bipolar mania. D(2) and D(3) antagonism may be involved in the mechanisms of the therapeutic response to antipsychotics in mania.     

The immunological axis in heart failure: importance of the leukocyte differential

The important role of the immune system and inflammation in the pathophysiology of heart failure (HF) is becoming increasingly appreciated. We have reviewed the prognostic significance of under-recognized aspects of the leukocyte differential in HF, including lymphocytes, monocytes, eosinophils and mast cells. Studies to date evaluating lymphocyte counts in both chronic and hospitalized HF patients have consistently shown worse prognosis associated with low lymphocyte counts, despite widely heterogeneous study designs. Limited data suggest elevations in monocyte-derived cytokines and serum monocyte count may be predictive of poor outcomes in HF. Further data are required to better define the relationship between eosinophils, mast cells and HF. Leukocyte differentials are widely available, simple, inexpensive and appear to have independent prognostic significance, beyond traditional risk factors. Enhanced sympathetic activation and increased circulating cytokine levels (particularly tumor necrosis factor) have been implicated in the variability of leukocyte subpopulations. To date, immune-modulators targeting these mediators have been largely unsuccessful in improving cardiovascular outcomes in HF. Given the potential role of the immunological axis in HF, there may be an unmet need for novel therapeutic agents that can safely and effectively ameliorate these leukocyte derangements and perhaps improve the unacceptably high event rate in this population. Variations in leukocyte differentials may identify a high-risk subset of patients that may benefit from tailored immune therapies.     

Neurocognitive and clinical predictors of functional outcome in patients with schizophrenia and bipolar I disorder at one-year follow-up

OBJECTIVE: Many studies have reported that cognitive ability may be predictive of the functional outcome for patients with schizophrenia. However, no study has prospectively examined these aspects in schizophrenia and bipolar disorders simultaneously. The present study attempted to analyze if neurocognition and clinical status predicts the real-life functioning for patients with schizophrenia or bipolar I disorder, using a longitudinal design. METHOD: Forty-seven schizophrenic and 43 bipolar I outpatients were assessed twice with a neurocognitive battery (Executive Functions, Working Memory, Verbal Memory, Visual Memory, Visual-Motor Processing, Vigilance, Vocabulary and Motor Speed tasks), clinical scales (the Positive and Negative Symptom Scale, the Hamilton Rating Scale for Depression and the Clinician Administered Rating Scale for Mania) and functional outcome measures (the Global Assessment of Functioning Scale, the WHO's Disability Assessment Scale and occupational adaptation level) over a one-year follow-up period. The cognitive performance of the patients was compared, at baseline and one year later, with that of 25 healthy subjects. RESULTS: In schizophrenia patients, global functioning one year later was predicted by a composite neurocognitive score and three specific domain (verbal memory, motor speed, vocabulary). Symptoms appeared to explain less of the variance in functioning. In bipolar I patients, changes in the composite neurocognitive score over one year, deficits in the visual/motor processing domain, severity of symptoms (psychotic, excitatory and affective symptoms) and premorbid adjustment at the first assessment were the variables that better predicted functioning or disability changes over follow-up period. CONCLUSIONS: Although the relationships between cognition, symptoms and functional capacity differ for schizophrenia or bipolar I patients, neuropsychological performance seems to be a principal longitudinal predictor of functioning in both disorders. Baseline neurocognition and cognitive changes over 12 months predicted changes in functioning over the same period, but only in bipolar I patients. These cognitive domains could be potential neurocognitive endophenotypes (endophenocognitypes) with regard to bipolar I disorder.     

Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn's disease

Crohn's disease is a chronic, inflammatory disease of the intestinal mucosa. Although intestinal bacteria are implicated in disease pathogenesis, the etiology is still unclear. The main location of disease is the small intestine (ileum) and the colon. Ileal disease has been linked to a mutation in the NOD2 gene. Defensins are antimicrobial peptides and in the ileum, are mainly expressed in Paneth cells, epithelial cells that also express NOD2. In the colon, defensins are expressed by enterocytes or metaplastic Paneth cells. Crohn's disease patients with ileal involvement, compared with controls or Crohn's patients without ileal involvement, have diminished expression of ileal Paneth cell defensins. This decrease is even more pronounced in Crohn's patients displaying a NOD2 mutation. In contrast, Crohn's disease of the colon is characterized by an impaired induction of beta-defensins in enterocytes. The colonic expression of the constitutive beta-defensin 1 is also decreased in the inflamed colonic mucosa, but this decrease is less specific to Crohn's disease, as it can also be found in ulcerative colitis patients. In conclusion, the regional localizations of Crohn's disease, ileal or colonic disease, can be linked to different defensin profiles. Crohn's disease of the ileum is associated with diminished defensin expression in Paneth cells. Crohn's disease of the colon is associated with diminished beta-defensin expression in enterocytes. Thus, it can be speculated that decreased defensin levels lead to a weakened intestinal barrier function to intestinal microbes and might be crucial in the pathophysiology of Crohn's disease.     

Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model

BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies.