Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

Objective

Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

Methods

AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

Results

Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue.

Conclusions

The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.     

Mental health first aid training for the Chinese community in Melbourne,Australia: effects on knowledge about and attitudes toward people with mental illness

Background  

The aim of this study was to investigate in members of the Chinese community in Melbourne the impact of Mental Health First Aid (MHFA) training on knowledge about mental disorders and on attitudes to people with mental illness. The hypotheses were that at the end of the training participants would have increased knowledge of mental disorders and related treatments, and decreased negative attitudes towards people with mental disorders.     

Disrupted functional connectivity for controlled visual processing as a basis for impaired spatial working memory in schizophrenia

Although regional brain abnormalities underlying spatial working memory (SWM) deficits in schizophrenia have been identified, little is known about which brain circuits are functionally disrupted in the SWM network in schizophrenia. We investigated SWM-related interregional functional connectivity in schizophrenia using functional magnetic resonance imaging (fMRI) data collected during a memory task that required analysis of spatial information in object structure. Twelve schizophrenia patients and 11 normal control subjects participated. Patients had SWM performance deficits and deficient neural activation in various brain areas, especially in the high SWM load condition. Examination of the covariation of regional brain activations elicited by the SWM task revealed evidence of functional disconnection between prefrontal and posterior visual association areas in schizophrenia. Under low SMW load, we found reduced functional associations between dorsolateral prefrontal cortex (DLPFC) and inferior temporal cortex (ITC) in the right hemisphere in patients. Under high SWM load, we found evidence for further functional disconnection in patients, including additional reduced functional associations between left DLPFC and right visual areas, including the posterior parietal cortex (PPC), fusiform gyrus, and V1, as well as between right inferior frontal cortex and right PPC. Greater prefrontal-posterior cortical functional connectivity was associated with better SWM performance in controls, but not in patients. These results suggest that prefrontal-posterior functional connectivity associated with the maintenance and control of visual information is central to SWM, and that disruption of this functional network underlies SWM deficits in schizophrenia.     

Development and validation of an algorithm for identifying prolonged mechanical ventilation in administrative data

Patients requiring prolonged mechanical ventilation (PMV) are a subset of critically ill patients with high resource utilization and poor long-term outcomes. We sought to develop an algorithm for identifying patients receiving PMV, defined as either 14 or 21 days of mechanical ventilation, in administrative and claims data. The algorithm was derived in mechanically ventilated patients at an academic medical center (n = 1,500) and validated in patients with community-acquired pneumonia in a multi-center clinical registry (n = 20,370), with further evaluation in the Pennsylvania discharge database (n = 62,383). The final algorithm combined the International Classification of Diseases codes for mechanical ventilation, diagnosis related groups for ventilation and tracheostomy, and intensive care unit length of stay. In the derivation dataset the algorithm was highly sensitive (14 days = 92.4%; 21 days = 97.6%) and specific (14 days = 91.6%, 21 days = 92.1%). The definition continued to perform well in the validation dataset (14 days: sensitivity = 87.6%, specificity = 88.5%). In both the derivation and validation datasets the negative predictive value was over 95% and positive predictive values ranged from 60% to 70%. In state discharge data the algorithm identified a cohort of patients with high costs and frequent discharge to skilled care facilities. Administrative data can be used to accurately identify populations of patients receiving PMV.