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To assess influenza symptoms, adherence to mask use recommendations, absenteesm and presenteeism in acute care healthcare workers (HCWs) during influenza epidemics.
The TransFLUas influenza transmission study in acute healthcare prospectively followed HCWs prospectively over 2 consecutive influenza seasons. Symptom diaries asking for respiratory symptoms and adherence with mask use recommendations were recorded on a daily basis, and study participants provided midturbinate nasal swabs for influenza testing.
In total, 152 HCWs (65.8% nurses and 13.2% physicians) were included: 89.1% of study participants reported at least 1 influenza symptom during their study season and 77.8% suffered from respiratory symptoms. Also, 28.3% of HCW missed at least 1 working day during the study period: 82.6% of these days were missed because of symptoms of influenza illness. Of all participating HCWs, 67.9% worked with symptoms of influenza infection on 8.8% of study days. On 0.3% of study days, symptomatic HCWs were shedding influenza virus while at work. Among HCWs with respiratory symptoms, 74.1% adhered to the policy to wear a mask at work on 59.1% of days with respiratory symptoms.
Respiratory disease is frequent among HCWs and imposes a significant economic burden on hospitals due to the number of working days lost. Presenteesm with respiratory illness, including influenza, is also frequent and poses a risk for patients and staff.
Background: For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps program helps people with dementia and their caregivers learn to use tablet computers and find user-friendly apps that facilitate self-management and engagement in meaningful activities. This definitive trial builds on previous feasibility pilot trials of FindMyApps and further evaluates cost-effectiveness.
Method: This is a protocol for a non-blinded randomized controlled trial (RCT) with two arms (intervention and usual care). 150 dyads (person with dementia and their carer) will be recruited. Participants must be resident in the community, with a diagnosis of Mild Cognitive Impairment or mild dementia (Mini Mental-State Examination 17-26, or Global Deterioration Scale 3-4. Dyads will be randomly assigned in equal proportions to receive either the FindMyApps intervention (experimental arm) or usual care (control arm). Primary outcomes measured at 3 months will be: patient self-management and social participation; caregiver sense of competence. Data will be collected through questionnaires filled in by the researcher (patient outcomes) or participants themselves (carer outcomes). In addition to a main effect analysis, a cost-effectiveness analysis will take place. In line with Medical Research Council (MRC) guidance for the evaluation of complex interventions, a process analysis will be undertaken, to identify factors that may influence trial outcomes. Semi-structured interviews and remotely collected data regarding use of the FindMyApps app will support the process analysis.
Result: Results of this study are expected in 2022. The study will be adequately powered to detect at least a moderate effect size of the intervention with respect to the primary outcomes.
Conclusion: This study will investigate the effectiveness and cost-effectiveness of the FindMyApps intervention. The results of the study will provide strong evidence to support or oppose scaling up implementation of the intervention. This is also an example of how the MRC framework for the evaluation of complex interventions can be implemented in practice. In a field which is often criticized for a lack of high quality evidence, randomized controlled trials should be applied more frequently designed for the robust and transparent evaluation of digital tools and technologies.
To determine whether combinations of diagnosis and procedures codes can improve the detection of prosthetic hip and knee joint infections from administrative databases.
We performed a validation study of all readmissions from January 1, 2010, until December 31, 2016, following primary arthroplasty comparing the diagnosis and procedure codes obtained from an administrative database based upon the International Classification of Disease, Tenth Revision (ICD-10) to the reference standard of chart review.
Four tertiary-care hospitals in Toronto, Canada, from 2010 to 2016.
Individuals who had a primary arthroplasty were identified using procedure codes.
Chart review of readmissions identified the presence of a prosthetic joint infection and, if present, the surgical procedure performed.
Overall, 27,802 primary arthroplasties were performed. Among 8,844 readmissions over a median follow-up of 669 days (interquartile range, 256–1,249 days), a PJI was responsible for or present in 586 of 8,844 (6.6%). Diagnosis codes alone exhibited a sensitivity of 0.88 (95% CI, 0.85–0.92) and positive predictive value (PPV) of 0.78 (95% CI, 0.74–0.82) for detecting a PJI. Combining a PJI diagnosis code with procedure codes for an arthroplasty and the insertion of a peripherally inserted central catheter improved detection: sensitivity was 0.92 (95% CI, 0.88–0.94) and PPV was 0.78 (95% CI, 0.74–0.82). However, procedure codes were unable to identify the specific surgical approach to PJI treatment.
Compared to PJI diagnosis codes, combinations of diagnosis and procedure codes improve the detection of a PJI in administrative databases.
Modern machine learning methods have the potential to supply industrial product lifecycle management (PLM) with automated classification of product components. However, there is only little work in the literature on this topic. We propose to apply supervised machine learning on component meta-data. By analysing an industrial case study, we identify requirements and opportunities for automating classification, e.g. in part numbers and product structures. We validate our novel approach through a classification experiment comparing four machine learning methods on a realistic component dataset.
Pharmacogenetics in schizophrenia comprises pharmacokinetical and pharmacodynamical aspects as well as an approach to identify candidate genes associated with therapy response or side effects. Firstly focussing on classical drug targets like dopaminergic or serotonergic receptors, currently also developmental and regulatory genes presumably associated with effects of antipsychotic therapy are identified. The aim of this study was to investigate associations between therapy response in schizophrenic patients and different polymorphisms previously been identified within a genome wide array in rodents treated with MK-801 and/or haloperidol combined with some well-known schizophrenia candidate genes. We genotyped for 200 different polymorphisms in 285 schizophrenic patients, who were treated with different antipsychotics within randomized controlled trials. Psychopathology was measured weekly using the PANSS scale. Correlations between psychopathology and genotypes were calculated by using a linear model (ANCOVA).
We found significant associations between some well-known candidate genes (e.g. D2-, 5HT1A-, and α1A-receptors) and different PANSS subscales at baseline and after four weeks of antipsychotic treatment considered as therapy response. Furthermore we also identified several significant associations between some genes introduced from the animal model and psychopathology at baseline and towards therapy response. Some of them were formerly described in the literature (e.g. Homer1, Phospholipase C and Transthyretin), but most of them have not been related to schizophrenia or antipsychotic treatment by now (e.g. PLEKHA6, CLIC6 and SOSTDC1).
This indicates an involvement of genes in the pathophysiology of schizophrenia apart from yet known candidate genes and might further help in detecting differential therapy response in individuals with schizophrenia.
Accumulating evidence suggests that deficits of visual selective attention may already occur at early stages of Alzheimer's disease (AD) like the prodromal phase of mild cognitive impairment (MCI).
Our study investigated visual selective attention in amnestic MCI and probable AD patients compared to healthy elderly controls. Groups were matched for age, gender and education. In combination with Bundesen's ‘theory of visual attention’, two mathematically independent and quantitative parameter estimates were derived from a partial report of briefly presented letter arrays: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and right hemifield.
Compared to controls, MCI patients showed significantly reduced top-down controlled selection which further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. The majority of patients was biased to the left. Across MCI and AD patients, carriers of the apolipoprotein E ɛ4 allele (ApoE4) revealed a leftward spatial bias. The leftward bias was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. ApoE4-negative subjects showed balanced attentional weighting.
These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal cortico-cortical networks. Accompanying, an early interhemispheric asymmetry in temporo-parietal cortical interactions might cause a pathological spatial bias. As the inheritance of ApoE4 is associated with asymmetric parietal metabolism, a pathological spatial bias may function as early cognitive marker for detecting probable AD subjects.
Since the introduction of second generation antipsychotics (SGA) extrapyramidal-motor symptoms (EPS) have become a lesser problem in the treatment of schizophrenic patients. Yet, some SGAs display these adverse events and first generation antipsychotics are still widely used. Several genetic polymorphisms have been found to be associated with the occurance of EPS.
In this study we tried to identify genes related to EPS from an animal model and then replicated the findings in schizophrenic patients.
To identify new genes and show their relevance in the treatment of schizophrenic patients.
Rats were treated with haloperidol or saline and differential gene expression was assessed by using microarrays. We genotyped 285 schizophrenic patients for candidate genes and differentially expressed genes derived from the animal model. All patients were treated monotherapeutically with different antipsychotics within randomized controlled trials. EPS were assessed weekly using the ESRS and BAS. We used a linear model (ANCOVA) with PANSS total at baseline, type of medication and premedication as covariates for all investigated SNP's.
We found several SNPs to be associated with the occurance of EPS. The best results were obtained for SNPs within the genes of Phospholipase C epsilon 1 (PLCe1), Methionine Sulfoxide Reductase B3 (MSRB3), Chloride Intracellular Channel 6 (CLIC6), Prolactin Receptor (PRLR) and Dopamine Receptor D4 (DRD4). Effect sizes were between 1.7 and 4.9.
We could replicate some findings of the literature and identified four new genes possibly related to EPS. Some of these genes were recently related to schizophrenia.
At present there is a paucity of standardised group behaviour therapy approaches targeting different kinds of personality disorders. On this background, our research group developed a new manualised treatment approach ("Schema-focused Emotive Behavioral Therapy"; SET), which integrates schematherapeutic, emotion-focused, cognitive and behavioural therapy methods. A multi-centre RCT-study evaluated SET based on a sample of 93 patients with personality disorders of clusters B and C. This study compared SET (n=47) with a classical Social Skills Training (SST, n=46) over 30 sessions. Patients were assessed before and after treatment and one year after study intake (follow-up). SET showed significantly higher improvements in several domains such as interpersonal behaviour, emotional coping, and symptomatic impairments. Clinically relevant effects on the SET occurred both in a reduction of the suffering from the disorder, severeness of the disorder, and hope for improvement. Furthermore, SET obtained a highly significant reduction of the dropout rate and a significantly increased use of therapy. Similar results for both comparison groups were found regarding behavioural coping and self-effectiveness. Results indicate that SET both entails a high acceptance of treatment and offers an adequate and effective group therapy for patients with personality disorders. From a clinical and economic point of view, SET promises to significantly contribute to mental health care.
Childhood Attention deficit hyperactivity disorder (ADHD) symptomatology persists in a substantial proportion of cases into adult life. ADHD is highly heritable but the etiology of ADHD is complex and heterogeneous, involving both genetic and non-genetic factors. In the present paper we analyzed the influence of both genetics and adverse life events on severity of ADHD symptoms in 110 adult ADHD patients. Subjects were genotyped for the norepinephrine transporter (NET), the Catechol-O-methyltransferase (COMT), the serotonin transporter promoter polymorphism (SERTPR) and the more rare A/G variant within SERTPR. Three main outcomes were obtained: (1) adverse events showed a small but positive correlation with current ADHD severity; (2) NET, COMT and the A/G variant within SERTPR were not associated with ADHD severity; (3) taking into account stressors, the long (L) SERTPR variant showed a mild effect on ADHD, being associated with an increased severity, particularly as regard affective dysregulations; on the other hand, in subjects exposed to early stressors, it showed a protective effect, as compared to the S variant (see table). In conclusion, our data support the role of environmental factors in adult ADHD symptomatology. SERTPR may be involved in some features of the illness and act as a moderator of environmental influences in ADHD.
In neuroleptic long-term medication, only part of the patients accept regular intake of neuroleptic drugs. The question is whether an interval medication regimen as opposed to continuous medication can help to reduce drop outs in patients with critical attitudes towards long-term medication. In a 2-year prospective study, 122 patients were randomised to an interval and 164 to a continuous neuroleptic medication regimen. The drop out rates were 62.5% in the interval and 53.7% in the continuous medication group. Drop outs generally show more negative attitudes towards treatment. Patients with negative attitudes do not do better under interval medication. Moreover, this regimen even requires more cooperation and trust in terms of the necessity of medication on the part of the patient compared to the continuous medication regimen. Interval medication therefore is a strategy which can only be successful in highly cooperative, but not in treatment-reluctant patients.
During recent years the treatment of personality disorders has increasingly come into focus. As the psychotherapeutic interventions are still limited with respect to these demanding disorders there is a considerable need for further efficacy and, particularly, therapy process investigations. A promising approach is the development of integrated psychotherapy which combines cognitive-behavioral interventions with further change mechanisms such as the clarification of maladaptive schemata. On top of that, interventions should maintain a focus on emotional aspects of the therapeutic alliance (emotion regulation). In a study on “Schema-focused Emotive Behavioral Therapy” (SET), 93 patients with personality disorders of clusters B (predominantly narcissistic and Borderline PS) and C (avoidant and dependent PS) were randomised into one arm with SET group therapy and a control arm with manualised social skills training (SST). Therapies lasted for approximately 30 two-hour sessions.
Therapy process was closely monitored using therapy session reports both from the patients' and therapists' perspectives. Therapy outcome was assessed prior to and after therapy.
We report here on the change mechanisms, which were derived from modeling therapy session reports with novel time series methods (vector autoregression based on the estimation of session-to-session changes). It was found that the two therapy approaches differed with respect to change mechanisms. In SET (yet not in SST) therapy groups, clarification and insight reduced feelings of being rejected and disrespected, which was a major concern of many patients. In addition to this, a contrast was found between the prototypical therapy processes of cluster B and C patients. In conclusion, these results lay the ground for a disorder-specific application of integrated psychotherapy in personality disorders.
Agomelatine is a new antidepressive drug, that is successfully applied in therapy of insomnia and depression. Until now, there has been no report on its application as add-on medication in therapy for the withdrawl ob benzodiazepine.
We are reporting a case of a forty-year-old male patient who was treated with Agomelatine in lorazepam withdrawl therapy. He showed a considerabel reduction of craving as well as of insomnia and vegetative symptoms.
Therefore there is the question if the substance has its own anti-craving component and to what extent the melatonin-receptor profile is involved.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
Soluble Interleukin-6 receptor (sIL-6R) levels are strongly related to the levels of Interleukin-6 (IL-6), and sIL-6Rs increase the immune activating properties of IL-6. We estimated sIL-6R serum levels in 25 schizophrenic patients and 25 healthy controls. In the patients, SIL-6R-CSF levels were also measured. The psychopathology was rated according to the AMDP system. We found a significant correlation between serum and cerebrospinal fluid (CSF) levels of sIL-6R, suggesting that serum levels may be a meaningful marker for the central action of sIL-6R. Moreover, significant correlations between the paranoid-hallucinatory syndrome and sIL-6R levels both in serum and CSF were observed. This finding suggests that IL-6 plays a role in the paranoid-hallucinatory symptomatology in schizophrenia. This can be understood regarding the influence of IL-6 to the catecholaminergic neurotransmission. The downregulating effects of neuroleptic treatment to sIL-6R demonstrate that the sIL-6R levels are decreased in the whole group of schizophrenic patients compared to controls.
Face processing is crucial for social interaction, but impaired in schizophrenia in terms of delays and misperceptions of identity and affective content. One important functional region for early stages of human face processing is the right fusiform face area. Thus, this region might be affected in schizophrenia. Aim of the study was to investigate whether face processing deficits are related to dysfunctions of the right fusiform face area in schizophrenics compared to controls.
In a rapid event-related fMRI design encoding of new faces as well as the recognition of newly learned, famous, and unknown faces was investigated in 13 schizophrenics and 21 healthy controls. Region of interest analysis was applied to each individual's right fusiform face area and tested for group differences.
Controls displayed more BOLD activation during the memorization of faces that were later successfully recognized. In schizophrenics this effect was not present. During the recognition task schizophrenics had lower BOLD responses, less accuracy, as well as longer reaction times to famous and unknown faces.
Our results support the hypothesis that impaired face processing in schizophrenia is related to early stage deficits during the encoding and immediate recognition of faces.
A proinflammatory state in a subgroup of depressed patients has been reported repeatedly (e.g. increased interleukin-6 and tumour necrosis factor-alpha). COX-2 inhibitors down-regulate increased inflammatory markers and are therefore investigated as an add-on therapy in depression. Proinflammatory cytokines and/or kynurenine metabolites may predict the outcome of treatment with COX-2 inhibitors.
To prove or disapprove the hypothesis of a better therapy response in the group of add-on celecoxib to sertraline, particularly in patients with a more pronounced proinflammatory state at baseline. The aim is to find a biological predictor (cytokines and/or kynurenine metabolites) for treatment outcome.
This is a dual-center, randomized, double-blind, placebo-controlled, parallel group phase IIa study. It investigates the mean change in clinical outcome and in serum cytokine and kynurenine levels from baseline to endpoint (week 6) in patients with major depression (HAMD-17 ≥ 22) treated with sertraline plus celecoxib versus sertraline plus placebo for six weeks. 51 depressed patients of both gender, aged between 18 and 60 years without any recent inflammatory disease were enrolled. The study comprises six study visits (6x ratings, 3x blood collections) during six weeks of treatment and a follow-up visit 10 weeks after baseline. Cytokines were measured by Enzyme-linked Immunosorbent Assay (ELISA), kynurenine and its metabolites by High Performance Liquid Chromatography (HPLC).
Results and Conclusion
The study was completed quite recently and the results are in progress.
Preclinical and first clinical studies suggested that the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen might be effective in the treatment of alcohol dependence. However, previous randomized controlled trials have reported inconsistent results, possibly related to the low to medium dosages of baclofen used in these studies.
To assess the efficacy and safety of individually titrated high-dose baclofen (30-270 mg/d) for the treatment of alcohol dependence.
Fifty-six alcohol-dependent patients were randomized to a double-blind treatment with individually titrated baclofen or placebo. Multiple primary outcome measures were total abstinence and cumulative abstinence duration during a 12-week high-dose phase.
Preliminary results of this clinical trial will be presented.
Brain-derived neurotrophic factor (BDNF) plays important roles in neurotransmitter release and synaptic plasticity and has been hypothesized to be involved in the development and maintenance of addictive disorders. Also, alterations in secretion of stress hormones within the <a name="_Hlk388856744">hypothalamic–pituitary–adrenal </a>(HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might modulate behavioural responses to substances of abuse. Therefore, we investigated alterations of BDNF expression and HPA axis activity in non-substance-related addictive disorders, i.e. pathological gambling (PG) and Internet use disorder (IUD).
We measured serum BDNF levels, plasma levels of copeptin, a vasopressin (AVP) surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with PG (n=14), IUD (n=11) and carefully matched healthy controls for PG (n=13) and IUD (n=10).
BDNF serum levels were significantly increased in patients with PG in comparison to healthy control subjects (p = 0.016). Furthermore, cortisol plasma levels correlated negatively with the PG-YBOCS total severity score (r<sup>2</sup> = -.626, p = .039) in patients with PG. There was no significant difference in BDNF serum levels of patients with IUD in comparison to control subjects. Plasma levels of copeptin, ACTH and cortisol in patients with PG and IUD did not differ among groups.
These preliminary results might suggest that the pathophysiology of PG shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in IUD.