Differences In Duration Of Illness Research Articles

Tissue Proteomic Analysis Identifies Mechanisms and Stages of Immunopathology in Fatal COVID-19.

Immunopathology occurs in the lung and spleen in fatal coronavirus disease (COVID-19), involving monocytes/macrophages and plasma cells. Antiinflammatory therapy reduces mortality, but additional therapeutic targets are required. We aimed to gain mechanistic insight into COVID-19 immunopathology by targeted proteomic analysis of pulmonary and splenic tissues. Lung parenchymal and splenic tissue was obtained from 13 postmortem examinations of patients with fatal COVID-19. Control tissue was obtained from cancer resection samples (lung) and deceased organ donors (spleen). Protein was extracted from tissue by phenol extraction. Olink multiplex immunoassay panels were used for protein detection and quantification. Proteins with increased abundance in the lung included MCP-3, antiviral TRIM21, and prothrombotic TYMP. OSM and EN-RAGE/S100A12 abundance was correlated and associated with inflammation severity. Unsupervised clustering identified “early viral” and “late inflammatory” clusters with distinct protein abundance profiles, and differences in illness duration before death and presence of viral RNA. In the spleen, lymphocyte chemotactic factors and CD8A were decreased in abundance, and proapoptotic factors were increased. B-cell receptor signaling pathway components and macrophage colony stimulating factor (CSF-1) were also increased. Additional evidence for a subset of host factors (including DDX58, OSM, TYMP, IL-18, MCP-3, and CSF-1) was provided by overlap between 1) differential abundance in spleen and lung tissue; 2) meta-analysis of existing datasets; and 3) plasma proteomic data. This proteomic analysis of lung parenchymal and splenic tissue from fatal COVID-19 provides mechanistic insight into tissue antiviral responses, inflammation and disease stages, macrophage involvement, pulmonary thrombosis, splenic B-cell activation, and lymphocyte depletion.

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials

ObjectiveTo evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults.MethodSeventeen English and Chinese databases were...

Demographic and clinical variables associated with response to clozapine in schizophrenia: a systematic review and meta-analysis.

Clozapine is the only licensed pharmacotherapy for treatment-resistant schizophrenia. However, response to clozapine is variable. Understanding the demographic and clinical features associated with response to clozapine may be useful for patient stratification for clinical trials or for identifying patients for earlier initiation of clozapine. We systematically reviewed the literature to investigate clinical and demographic factors associated with variation in clozapine response in treatment-resistant patients with schizophrenia spectrum disorders. Subsequently, we performed a random-effects meta-analysis to evaluate differences in duration of illness, age at clozapine initiation, age of illness onset, body weight and years of education between clozapine responders and non-responders. Thirty-one articles were eligible for qualitative review and 17 of these were quantitatively reviewed. Shorter duration of illness, later illness onset, younger age at clozapine initiation, fewer hospitalisations and fewer antipsychotic trials prior to clozapine initiation showed a trend to be significantly associated with a better response to clozapine. Meta-analysis of seven studies, totalling 313 subjects, found that clozapine responders had a significantly shorter duration of illness compared to clozapine non-responders [g = 0.31; 95% confidence interval (CI) 0.06-0.56; p = 0.01]. The results imply that a delay in clozapine treatment may result in a poorer response and that a focus on prompt treatment with clozapine is warranted.

M212. A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICAL VARIABLES ASSOCIATED WITH RESPONSE TO CLOZAPINE IN TREATMENT RESISTANT SCHIZOPHRENIA

BackgroundApproximately one third of patients with schizophrenia display suboptimal response to two trials of non-clozapine antipsychotic medication and may be termed treatment resistant. Clozapine is the only licensed pharmacotherapy for treatment resistant schizophrenia, but response to clozapine is variable and can only be determined through a trial of treatment. Understanding demographic and clinical sources of varied response to clozapine may be useful in the optimisation of clinical treatment algorithms and stratification of patient groups for clinical trials of early use of clozapine.MethodsWe systematically reviewed literature to investigate clinical and demographic factors associated with variation in clozapine response. Articles were eligible for review if they reported differences in clozapine response as a function of baseline variables within patient samples of schizophrenia spectrum disorders. In a second step, a random-effects meta-analysis to study group mean differences in age, age of onset and duration of illness between clozapine responders and non-responders was performed.ResultsThirty-one articles were eligible for qualitative review. The systematic review found that a poorer response to clozapine was associated with older age at clozapine initiation, younger age at illness onset and longer delay in clozapine initiation. A higher number of previous hospitalisations and antipsychotic trials prior to treatment with clozapine were also associated with poorer outcomes. Both systematic review and meta-analysis identified that longer durations of illness before clozapine initiation were associated with worse clinical outcomes. In a total sample of 313 participants (n = 158 responders), clozapine responders had a significantly shorter duration of illness than non-responders (g = - 0.31; 95% CI, 0.06 - 0.56; p = 0.02). Analysis was then limited to studies with a minimum follow-up period of 12 weeks to align with the recommended amount of time to monitor clozapine response. The difference in duration of illness between responder versus non-responder groups remained significant and overall effect size increased (g = - 0.42; 95% CI, 0.17 – 0.67; p < 0.001). Between study heterogeneity was low (Q = 3.59, I2 = 0%, P = 0.61).DiscussionThe results imply that delay in clozapine treatment is associated with worse response and support the view that initiation of clozapine earlier in illness may be beneficial. Although we cannot make causal assertions from the data presented, poor response to clozapine when prescribed after a longer delay is likely due to a combination of factors; including the effects of sustained active symptoms on neurobiological integrity, social functioning and self-care. Given evidence that early non-response to conventional antipsychotics predicts a later diagnosis of treatment resistance and poorer outcomes, identifying treatment resistance and prescribing clozapine earlier in the illness course would prevent unnecessary loss of time in the treatment of refractory psychosis. Current research into clinical variables associated with clozapine response is limited to few studies but future investigation into the predictive value of these variables is warranted. This is important given the relative ease and low-cost clinical information can be obtained from acutely unwell patient groups who may poorly tolerate more invasive research and clinical procedures.

History of Overweight/Obesity as Predictor of Care Received at 1-year Follow-Up in Adolescents With Anorexia Nervosa or Atypical Anorexia Nervosa

PurposePrevious research has indicated that patients with anorexia nervosa (AN) or atypical AN with premorbid history of overweight/obesity have greater weight loss and longer illness duration than patients with no such history. However, little is known about the association of premorbid overweight/obesity and receiving inpatient medical care during treatment for an eating disorder. MethodsUsing logistic regression, we sought to determine if history of overweight/obesity was associated with receiving inpatient medical care in a sample of 522 patients (mean age 15.5 years, 88% female) with AN/atypical AN. ResultsBinary results demonstrated greater percent weight loss (27.4% vs. 16.2%) and higher percent median body mass index (%mBMI, 99.8% vs. 85.2%) at presentation in those with a history of overweight/obesity (p < .001) but no difference in duration of illness (p = .09). In models adjusted for demographics and percent weight loss, history of overweight/obesity was associated with lower odds of receiving inpatient medical care (odds ratio .60 [95% confidence interval: .45–.80]) at 1-year follow-up. However, these associations were no longer significant after adjusting for %mBMI. Mediation results suggest that %mBMI fully mediates the relationship between history of overweight/obesity and inpatient medical care, in that those with a history of overweight/obesity are less likely to receive care due to presenting at a higher weight. ConclusionsOur findings suggest that, despite greater degree of weight loss and no difference in duration of illness, participants with a history of overweight/obesity are less likely to receive inpatient medical care.

Benfotiamine and alpha-lipoic acid in the treatment of cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus

The aim of this study was to assess the efficiency of benfotiamine and α-lipoic acid (α-LA) in the treatment of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (type 2 DM). We have examined 70 patients with type 2 DM with established CAN. Treatment groups were sex and age-matched, there was no difference in duration of illness, HbA1c levels. Patients with type 2 DM and CAN were divided into four treatment groups: group A received traditional hypoglycemic therapy (n=15, control group), group B (n=12), in addition to traditional therapy received benfotiamine 300 mg/day; patients from group C (n=18) – α-LA 600 mg/day; group D (n=15) – 300 mg/day of benfotiamine in combination with 600 mg/day α-LA. Duration of the study was 3 months. As a result, no significant difference in HbA1c concentrations in the blood of patients with type 2 DM and CAN before and after treatment was found. It was established, that assignment of benfotiamine to patients with type 2 DM and CAN was not associated with significant changes in LDL, HDL, TG, total cholesterol and leptin levels, but contributes significant decrease of IRI, hsCRP and TNF- α concentrations. Usage of α-LA in the complex treatment of patients with type 2 DM and CAN contribute to significant decrease of LDL, total cholesterol, IRI, leptin and TNF-α concentrations. Combined usage of benfotiamine and α-LA in patients with type 2 DM and CAN is accompanied by more significant decrease of LDL, total cholesterol, IRI, hsCRP and TNF-α and increase of HDL concentration. Obtained results suggest that the efficacy of combined treatment with benfotiamine and α-LA has no connection with the improvement of diabetes compensation, but are as result of the direct pharmacological agents effect on the investigated metabolic parameters level.

Mindfulness Training in a Heterogeneous Psychiatric Sample: Outcome Evaluation and Comparison of Different Diagnostic Groups

To examine outcome after mindfulness training in a heterogeneous psychiatric outpatient population and to compare outcome in different diagnostic groups. One hundred and forty-three patients in 5 diagnostic categories completed questionnaires about psychological symptoms, quality of life, and mindfulness skills prior to and immediately after treatment. The mixed patient group as a whole improved significantly on all outcome measures. Differential improvement was found for different diagnostic categories with respect to psychological symptoms and quality of life: Bipolar patients did not improve significantly on these measures. This finding could be explained by longer illness duration and lower baseline severity in the bipolar category. Mindfulness training is associated with overall improvement in a heterogeneous outpatient population. Differences in outcome between diagnostic categories may be ascribed to differences in illness duration and baseline severity.

Parkinsonian motor features distinguish the agrammatic from logopenic variant of primary progressive aphasia

BackgroundFew studies have assessed parkinsonian motor features across variants of primary progressive aphasia (PPA). Our objective was to compare degree of parkinsonian motor features between two PPA variants. MethodsParkinsonian motor features were assessed with the Unified Parkinson's Disease Rating scale in prospectively recruited PPA subjects, classified based on recently published criteria. Comparisons across groups were performed with Fisher's exact test for binary data and Mann–Whitney U test for continuous data. ResultsTwenty-three PPA subjects were diagnosed with logopenic (n = 11) or nonfluent/agrammatic (n = 12) aphasia. There were no significant differences in illness duration (agrammatic = 3.4 years; logopenic = 3.3 years) or age at onset (nonfluent/agrammatic = 67.3; logopenic = 62.0), but those with logopenic aphasia were more impaired on Mini-Mental State Examination (21.7/30 points vs. 26.1/30; p = 0.04). In contrast, those with logopenic aphasia had fewer parkinsonian motor features than those with agrammatic aphasia (5.7/132 vs. 16.8/132; p = 0.003) which was driven by bradykinesia (p = 0.02) and speech facial/expression (p = 0.04); less so rigidity (p = 0.06). Dysarthria was more frequent in the nonfluent/agrammatic subgroup. ConclusionsNonfluent/agrammatic subjects have more parkinsonian motor features than logopenic subjects, likely reflecting underlying tau pathology in the agrammatic variant.

Do antipsychotic medications reduce or increase mortality in schizophrenia? A critical appraisal of the FIN-11 study

Compared to the general population, people with schizophrenia are at risk of dying prematurely due to suicide and due to different somatic illnesses. The potential role of antipsychotic treatment in affecting suicide rates and in explaining the increased mortality due to somatic disorders is highly debated. A recent study of death registers in Finland compared the cause-specific mortality in 66,881 patients versus the total population (5.2 million) between 1996 and 2006, suggesting that antipsychotic use decreased all-cause mortality compared to no antipsychotic use in patients with schizophrenia, and that clozapine had the most beneficial profile in this regard ( Tiihonen et al., 2009). The benefits of clozapine were conferred by significant protective effects for suicide compared to perphenazine, whereas, a mixed group of ‘other’ antipsychotics, haloperidol, quetiapine and risperidone were reported to be associated with significantly higher all-cause mortality than perphenazine. By contrast, despite known differences in effects on cardiovascular risk factors, there were no significant differences between any of the examined antipsychotics regarding death due to ischemic heart disease. A number of methodological and conceptual issues make the interpretation of these findings problematic, including incomplete reporting of data, questionable selection of drug groups and comparisons, important unmeasured risk factors, inadequate control for potentially confounding variables, exclusion of deaths occurring during hospitalization leading to exclusion of 64% of deaths on current antipsychotics from the analysis, and survivorship bias due to strong and systematic differences in illness duration across the treatment groups. Well designed, prospective mortality studies, with direct measurement of and adjustment for all known relevant risk factors for premature mortality, are needed to identify risk and protective medication and patient factors and to, ultimately, inform clinical practice.

Differences in clinical presentation between norovirus genotypes in nursing homes

Background In healthcare settings, norovirus (NoV) outbreaks are predominated by genotype II.4 (GII.4) strains. Periodically, new variants of GII.4 emerge, causing a temporary increase of outbreaks. Objectives To study the relationship between symptoms and NoV genotype. Study design Data of 49 nursing homes which were monitored for NoV outbreaks in the winter seasons of 2005/2006 and/or 2006/2007 were used. Results Data on symptoms and duration of illness were available for 465 residents and 174 staff members from 28 NoV outbreaks. Genotype GII.4 was responsible for 21 outbreaks. Attack rates for residents seemed to be higher in GII.4 outbreaks compared to other genotypes. In outbreaks caused by GII.4, residents vomited more often than in outbreaks with other genotypes. They also had more often complaints of nausea, abdominal cramps, fever, and mucus in stool. The GII.4 2004 variant outbreaks showed higher percentages of nausea, stomach ache, and fever than outbreaks with the GII.4 2006a variant. Differences in duration of illness were not found. In nursing home staff, no clear differences were found between outbreaks caused by GII.4 and non-GII.4 NoVs. Conclusions Genotype GII.4 was found to be related to more symptomatic disease, including more residents vomiting, and to a lesser extent, higher attack rates among residents.

Frequency and Histopathologic Basis of Hepatic Surface Nodularity in Patients with Fulminant Hepatic Failure

To determine the frequency and histopathologic basis of hepatic surface nodularity at imaging in patients with fulminant hepatic failure. The committee on human research approved this HIPAA-compliant study and waived written informed consent. Thirty-five consecutive patients [24 female [mean age, 38 years +/- 19 (standard deviation); range, 1-67 years] and 11 male [mean age, 29 years +/- 22; range, 2-61 years]] with a mean age of 35 years +/- 20 (range, 1-67 years) who underwent liver transplantation for fulminant hepatic failure at our institution during a 5-year period were retrospectively identified. Pretransplant ultrasonographic (n = 38; three patients each had two studies) and computed tomographic (n = 2) studies were retrospectively and independently reviewed for hepatic surface nodularity. Liver explant histopathologic findings (n = 33; slides unavailable in two patients) were reviewed for cirrhosis and for the combination of alternating foci of confluent regenerative nodules and necrosis. Differences among patients with nodular versus smooth liver surfaces in the proportion with the two histopathologic findings were compared with Fisher exact test. Differences in illness duration and maximum liver biochemical indices were compared with Mann-Whitney Rank Sum test. Fifteen of 35 patients (43%) demonstrated hepatic surface nodularity at pretransplant imaging, none of whom had cirrhosis at histopathologic examination. One patient with a smooth liver surface had cirrhosis. Compared with those who had a smooth liver surface, patients with hepatic surface nodularity had a significantly greater proportion with the histopathologic finding of a combination of alternating foci of confluent regenerative nodules and necrosis (12 of 14 vs one of 19, P < .001), longer illness duration (31 days +/- 32 vs 13 days +/- 13, P = .029), and lower maximum liver biochemical indices. Hepatic surface nodularity is commonly seen at imaging in fulminant hepatic failure and usually reflects a combination of alternating foci of confluent regenerative nodules and necrosis; this is important because an erroneous radiologic diagnosis of cirrhosis in this setting could adversely affect transplantation status.

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors. Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A. Whether these different pharmacological actions produce different effects on brain structure remains unclear. We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based, nonrandomized sample of patients at the first psychotic episode. Subjects were recruited as part of a large epidemiological study (AESOP: aetiology and ethnicity in schizophrenia and other psychoses). We evaluated 22 drug-free patients, 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics. We used high-resolution MRI and voxel-based methods of image analysis. The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes. However, typicals seem to affect more extensively the basal ganglia (enlargement of the putamen) and cortical areas (reductions of lobulus paracentralis, anterior cingulate gyrus, superior and medial frontal gyri, superior and middle temporal gyri, insula, and precuneus), while atypical antipsychotics seem particularly associated with enlargement of the thalami. These changes are likely to reflect the effect of antipsychotics on the brain, as there were no differences in duration of illness, total symptoms scores, and length of treatment among the groups. In conclusion, we would like to suggest that even after short-term treatment, typical and atypical antipsychotics may affect brain structure differently.

Investigation of gestural and pantomime performance in chronic schizophrenic inpatients.

The present study compared the performance on apraxia tests and additional motor tasks between medicated chronic schizophrenic inpatients (n = 21) and healthy subjects (n = 21). Praxis testing did not reveal a clear-cut apractic syndrome in the patient group. The most striking difference between patients and healthy controls was the more frequent use of body parts as object (BPO) by schizophrenic patients (P < 0.0003). There was no significant difference in psychopathology between subgroups classified according to their BPO performance, although a tendency towards a difference in duration of illness and the actual hospitalization period existed between BPO subgroups. Schizophrenic patients performed more poorly than controls in frontal motor tasks: sequencing, including oral sequential movements, and reciprocal innervation. Frontal motor task performance tended to be related to the negative dimension of schizophrenia in accordance with previous studies. The data do not support the assumption that BPO performance is part of a multidimensional concrete attitude in schizophrenic patients. Nevertheless, this peculiarity in motor behaviour might be a link between neurophysiology and psychopathological phenomenology in schizophrenia. We therefore suggest further investigation focusing the performance of object-related pantomime movements in schizophrenic patients.

The Lewy-Body Variant of Alzheimer's Disease

At post-mortem, Lewy bodies (LBs) were found in the brainstem and neocortex of eight out of 65 patients who had been collected during a prospective long-term study on clinically diagnosed Alzheimer's disease. All eight patients had accompanying Alzheimer pathology which was less severe than in a sample of eight age- and sex-matched patients from the same study with neuropathologically verified Alzheimer's disease. Parkinsonian features were more common in patients with LBs. There were no particular differences in duration of illness, severity of cognitive impairment, presence of hallucinations, or fluctuations in the course of illness. Frontal cerebral atrophy was more marked in patients with LBs, as was the loss of neurons in the basal nucleus of Meynert and the substantia nigra. Cognitive performance correlated with the number of pigmented neurons in the substantia nigra. We conclude that the differential diagnosis of LB dementia should be considered in patients satisfying NINCDS-ADRDA criteria for Alzheimer-type dementia who show marked Parkinsonian features and a frontal accentuation of cerebral atrophy.