Spurious precision : variability in procedural validity of diagnostic procedures in psychotic disorders and implications for research and treatment

Very few studies have quantified the level of agreement among alternative diagnostic procedures that use a common set of fixed operational criteria. The authors examined the procedural validity of four independent methods of assigning DSM-III-R diagnoses of psychotic disorders. METHOD: The research was conducted as a satellite study to the DSM-IV Field Trial for Schizophrenia and Related Psychotic Disorders. The setting was the National Health and Medical Research Council Schizophrenia Research Unit's Early Psychosis Prevention and Intervention Centre, which focuses on first-episode psychosis. Consecutively admitted patients (N = 50) were assessed by independent raters who used four different procedures to determine a DSM-III-R diagnosis. These procedures were 1) the diagnostic instrument developed for the DSM-IV field trial, 2) the Royal Park Multidiagnostic Instrument for Psychosis, 3) the Munich Diagnostic Checklists, and 4) a consensus DSM-III-R diagnosis assigned by a team of clinician researchers who were expert in the use of diagnostic criteria. RESULTS: Concordance between pairs of diagnostic procedures was only moderate. Corresponding levels of percent agreement, however, ranged from 66% to 76%, with converse misclassification rates of 24%-34% (assuming one procedure to be "correct"). CONCLUSIONS: These findings have significant research and clinical implications. Despite the introduction of operationally defined diagnoses, there remained an appreciable level of differential classification or misclassification arising from variability in the method of assigning the diagnostic criteria rather than the criteria themselves. Such misclassification may impede neurobiological research and have harmful clinical effects on patients with first-episode psychosis.

The effects of specific educational preparation on emergency nurses` clinical decisions regarding supplemental oxygen administration

Abstract The use of supplemental oxygen by emergency nurses has important implications for patient outcomes, yet there is significant variability in oxygen administration practises. Specific education related to oxygen administration increases factual knowledge in this domain; however, the impact of knowledge acquisition on nurses' clinical decisions is poorly understood. This study aimed to examine the effect of educational preparation on 20 emergency nurses' decisions regarding the assessment of oxygenation and the use of supplemental oxygen. A pre-test/post-test, quasi-experimental design was used. The intervention was a written, self-directed learning package. The major effects of the completion of the learning package included no change in the number or types of parameters used by nurses to assess oxygenation, a significant decrease in the selection of simple masks, a significant increase in the selection of air entrainment masks, fewer hypothetical outcomes of unresolved respiratory distress and more hypothetical outcomes of decreased respiratory distress. As many nursing education programs are aimed at increasing factual knowledge, while experience remains relatively constant, a greater understanding of the relationship between factual knowledge and clinical decisions is needed if educational interventions are to improve patient outcomes.

2001 Volvo Award winner in clinical studies : effects of a media campaign on back pain beliefs and its potential influence on management of low back pain in general practice

Study Design. Quasi-experimental, nonrandomized, nonequivalent, parallel group-controlled study involving before and after telephone surveys of the general population and postal surveys of general practitioners was conducted, with an adjacent state used as a control group.


Objectives. To evaluate the effectiveness of a population-based intervention designed to alter beliefs about back pain, influence medical management, and reduce disability and workers’ compensation–related costs.


Summary of Background Data. A multimedia campaign begun during 1997 in Victoria, Australia, positively advised patients with back pain to stay active and exercise, not to rest for prolonged periods, and to remain at work.


Methods. The campaign’s impact on population beliefs about back pain and fear-avoidance beliefs was measured in telephone surveys, and the effect of the campaign on the potential management of low back pain by general practitioners was assessed by eliciting their likely approach to two hypothetical scenarios in mailed surveys. Demographically identical population groups in Victoria and the control state, New South Wales, were surveyed at three times: before, during, and after intervention in Victoria.


Results. The studies were completed by 4730 individuals in the general population and 2556 general practitioners. There were large statistically significant improvements in back pain beliefs over time in Victoria (mean scores on the Back Beliefs Questionnaire, 26.5, 28.4, and 29.7), but not in New South Wales (26.3, 26.2, and 26.3, respectively). Among those who reported back pain during the previous year, fear-avoidance beliefs about physical activity improved significantly in Victoria (mean scores on the Fear-Avoidance Beliefs Questionnaire for physical activity, 14, 12.5, and 11.6), but not in New South Wales (13.3, 13.6, and 12.7, respectively). General practitioners in Victoria reported significant improvements over time in beliefs about back pain management, as compared with their interstate colleagues. There were statistically significant interactions between state and time for 7 of 10 responses on management of acute low back pain, and for 6 of 10 responses on management of subacute low back pain.


Conclusion. A population-based strategy of providing positive messages about back pain improves the beliefs of the general population and general practitioners about back pain and appears to influence medical management.

Effects of N-acetylcysteine on substance use in bipolar disorder : a randomized placebo controlled clinical trial

Objective: To evaluate the effect of N-acetylcysteine (NAC) on substance use in a double-blind, placebo-controlled trial of NAC in bipolar disorder. It is hypothesised that NAC will be superior to placebo for reducing scores on the Clinical Global Impressions scale for Substance Use (CGI-SU).

Methods: Participants were randomised to 6-months of treatment with 2 g/day NAC (n = 38) or placebo (n = 37). Substance use was assessed at baseline using the Habits instrument. Change in substance use was assessed at regular study visits using the CGI-SU.

Results: Amongst the 75 participants 78.7% drank alcohol (any frequency), 45.3% smoked tobacco and 92% consumer caffeine. Other substances were used by fewer than six participants. Caffeine use was significantly lower for NAC-treated participants compared with placebo at week 2 of treatment but not at other study visits.

Conclusion: NAC appeared to have little effect on substance use in this population. A larger study on a substance using population will be necessary to determine if NAC may be a useful treatment for substance use.

Nocebo effects in the treatment of major depression: results from an individual study participant-level meta-analysis of the placebo arm of duloxetine clinical trials

BACKGROUND: The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events, and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning. METHOD: This study analyzed pooled clinical trial data in the placebo arms of controlled trials of antidepressant medications to investigate variables associated with the emergence of adverse outcomes in placebo-treated participants (N = 2,457). Specifically, we examined treatment-emergent adverse events (TEAEs) and discontinuation in placebo-treated individuals. Trials were commenced between 1993 and 2010 as studies of duloxetine versus active comparator and/or placebo. RESULTS: TEAEs were reported by 1,569 placebo-treated participants (63.9%), with 115 (4.7%) discontinuing from the studies due to TEAEs and 274 (11.2%) showing worsening of Hamilton Depression Rating Scale total score during placebo treatment. There was specifically no evidence to support the expectancy hypothesis, that reported TEAEs were influenced by adverse effects described in the clinical trials participant information and consent forms, or the conditioning hypothesis, that reported TEAEs would be influenced by adverse effect profiles of previous antidepressant medications used by these study participants. There was some evidence to suggest that people who had previously used complementary medications were more likely to report TEAEs. Variables specific to individual studies were the strongest predictors of TEAEs. DISCUSSION: In this study, TEAEs were very common among placebo-treated clinical trial participants. Unexpectedly, there was no evidence to associate TEAEs with adverse clinical outcomes, nor were the conditioning or expectancy hypotheses supported by these data. CONCLUSIONS: The nocebo effect is a common, covert, and poorly understood driver of clinical outcomes that requires further investigation.

Creatine supplementation and riluzole treatment provide similar beneficial effects in copper, zinc superoxide dismutase (G93A) transgenic mice

This study investigated the effects of riluzole (Ril), creatine (Cr) and a combination of these treatments on the onset and progression of clinical signs and neuropathology in an animal model of familial amyotrophic lateral sclerosis, the G93A transgenic mouse (n=13–17 per group). The onset of clinical signs was delayed (P<0.05) by about 12 days in all treatment groups compared with control; however, no differences occurred between treatments. All animals were killed at 199 days of age. At the end of the experimental period the severity of clinical signs was less (P<0.05) with all treatments compared with control. Again no differences between treatments were observed. The treatments had no effect on the number of neurons in ventral horns of the lumbar region of the spinal cord. Transgenic mice ingesting Cr displayed elevated (P<0.05) total Cr levels in cerebral hemispheres (5%) and spinal cord (8%), but not skeletal muscles. These data demonstrate that treatment with Ril and Cr were both effective in delaying disease onset and clinical disability. To the age of killing, no additional benefit was conferred by co-administration of Ril and Cr.

Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice

Postoperative pulmonary complications are the most frequent and significant contributor to morbidity, mortality, and costs associated with hospitalization. Interestingly, despite the prevalence of these complications in cardiac surgical patients, recognition, diagnosis, and management of this problem vary widely. In addition, little information is available on the continuum between routine postoperative pulmonary dysfunction and postoperative pulmonary complications. The course of events from pulmonary dysfunction associated with surgery to discharge from the hospital in cardiac patients is largely unexplored. In the absence of evidence-based practice guidelines for the care of cardiac surgical patients with postoperative pulmonary dysfunction, an understanding of the path ophysiological basis of the development of postoperative pulmonary complications is fundamental to enable clinicians to assess the value of current management interventions. Previous research on postoperative pulmonary dysfunction in adults undergoing cardiac surgery is reviewed, with an emphasis on the pathogenesis of this problem, implications for clinical nursing practice, and possibilities for future research.

Characterization of haemolytic phospholipase A2 activity in clinical isolates of Campylobacter concisus

A membrane-bound, haemolytic phospholipase A2 (PLA2) activity was detected in clinical strains of Campylobacter concisus isolated from children with gastroenteritis. The clinical strains were assigned into two molecular groups (genomospecies) based on PCR amplification of their 23S rDNA. This calcium-dependent, heat-stable, haemolytic PLA2 activity was detected in strains from both genomospecies. A crude haemolysin extract (CHE) was initially prepared from cellular outer-membrane proteins of these isolates and was further fractionated by ultrafiltration. The haemolytic activity of the extracted fraction (R30) was retained by ultrafiltration using a 30 kDa molecular mass cut-off filter, and was designated haemolysin extract (HE). Both CHE and HE had PLA2 activity and caused stable vacuolating and cytolytic effects on Chinese hamster ovary cells in tissue culture. Primers for the conserved region of pldA gene (phospholipase A gene) from Campylobacter coli amplified a gene region of 460 bp in all tested isolates, confirming the presence of a homologous PLA gene sequence in C. concisus. The detection of haemolytic PLA₂ activity in C. concisus indicates the presence of a potential virulence factor in this species and supports the hypothesis that C. concisus is a possible opportunistic pathogen.

Dietary counseling to increase natural folate intake: a ransomized placebo-controlled trial in free-living subjects to assess effects on serum folate and plasma total homocysteine.

BACKGROUND: The association between vascular disease and elevated plasma total homocysteine (tHcy) concentrations is caused, in part, by inadequate intakes of dietary folate. Increasing folate intake either through supplements or foods naturally rich in folates has been shown to decrease tHcy concentrations. OBJECTIVE: The aim of this study was to determine whether a similar reduction in tHcy was possible in free-living persons receiving dietary counseling. DESIGN: The study included a 4-wk placebo-controlled dietary intervention trial in which participants consumed either unfortified breakfast cereal (control group) or an extra 350 micro g folate derived from food/d (dietary group). Serum folate and tHcy concentrations in both groups were measured before and after the intervention period, and the concentrations in the dietary group were also measured 17 wk after the intervention period. RESULTS: During the 4-wk intervention, mean dietary folate intake in the dietary group increased from 263 (95% CI: 225, 307) to 618 micro g/d (535, 714), resulting in a mean increase in serum folate of 37% (15%, 63%) and a decrease in tHcy from 12.0 (10.9, 13.3) to 11.3 micro mol/L (10.2, 12.5). A further decrease in tHcy occurred in the dietary group during follow-up, with a final tHcy concentration of 9.7 micro mol/L (8.8, 10.8). CONCLUSIONS: Increasing natural folate intake improved folate status and decreased tHcy concentrations to an extent that may significantly reduce the risk of vascular disease. Dietary modification may have advantages over folic acid fortification because the altered food-consumption patterns lead to increased intakes of several vitamins and minerals and decreased intakes of saturated fatty acids.

Effects of a walking program in the psychiatric in-patient treatment setting: a cohort study.

Issue addressed: To assess the effectiveness of a walking program in a psychiatric in-patient unit. Method: In-patients at a private psychiatric unit were offered the opportunity to participate in a daily morning 40 minute walk led by an activity supervisor. After discharge, outcomes for patients who had regularly participated in the walking group (n=35) and patients who had not participated (n=49) were compared for length of stay during their period of admission and Clinical Global Impression - Severity (CGI-S) and  Depression Anxiety Stress Scales (DASS) scores measured at admission and discharge. This was a retrospective analysis of data collected routinely. Results: There were no significant differences between the two cohorts on most primary outcome measures, including length of stay, DASS scores at admission and at discharge and CGI-S scores at admission. Patients who had not participated in the walking group had a significantly lower score on a single measure, the CGI-S, than patients who had participated (p=0.001). Conclusions: This study showed no evidence that in-patients benefited from participating in the physical activity program. However, this must be  interpreted within the confines of a number of study limitations and, as such, the findings can neither support nor refute the effectiveness of physical activities.

Effects of gamma-tocopherol supplementation on thrombotic risk factors

Objective: The antioxidant activity of vitamin E is derived primarily from alpha-tocopherol (α-T) and gammatocopherol (γ-T). Results of epidemiological studies have demonstrated an inverse relationship between vitamin E intake and coronary disease. However, the results of clinical trials using α-T are equivocal. We determined the effect of 5 weeks of 100 mg/d or 200 mg/d γ-T supplementation on thrombotic markers such as platelet reactivity, lipid profile and the inflammation marker C-reactive protein (CRP). Methods and results: Fourteen healthy subjects consumed 100 mg/day while 13 consumed 200 mg/d of γ-T and 12 received placebo (soybean capsules with less than 5 mg/d γ-T) in a double-blinded parallel study design. Fasting pre and post dose blood samples were analysed. Blood γ-T concentrations increased significantly (p<0.05) relative to dose during the intervention period. Both groups receiving active ingredients showed significantly lower platelet activation after supplementation (p<0.05). Subjects consuming 100 mg/d γ-T had significantly decreased LDL cholesterol, platelet aggregation and mean platelet volume (MPV) (p<0.05). Little effect of γ-T was observed on other parameters. Conclusions: These data suggest that γ-T  supplementation may have a permissive role in decreasing the risk of
thrombotic events by improving lipid profile and reducing platelet activity.

The mother-daughter guilt dynamic : effects of type 1 diabetes during life transitions

Aim. The aim of the study was to explore and describe the strategies young women with type 1 diabetes used to manage life transitions. The paper describes one aspect of how guilt dynamic often operates between mothers and daughters and how the women managed the guilt dynamic to create stability in their lives.
Background. When a child is diagnosed with diabetes, major transitional changes occur in the relationships between the mother and her child. The changes affect the psychological and social aspects of their lives and have a major impact on how young women manage their diabetes. A guilt dynamic between mothers and young women with diabetes emerged as a major theme in a larger study that investigated how young women with diabetes managed life transitions. Although the literature indicates that mothers of chronically ill children experience guilt feelings towards their children, little research was identified that addressed the emotional dynamics between mothers and daughters with diabetes.
Design. Using grounded theory method, interviews were conducted with 20 women with type 1 diabetes and five mothers during 2002 and 2003. Constant comparative analysis was used to analyse the data and develop an in-depth understanding of the experience of living with diabetes during life transitions.
Findings. The findings revealed that guilt feelings created a two-way dependency between mothers and their daughters with diabetes. The two-way dependency involved feelings of being a burden to each other, difficulty balancing responsibilities for diabetes management, difficulty relinquishing emotional and social dependency especially during life transitions. In addition, these issues were rarely discussed openly with each other or with health professionals. The findings provide additional information about the human experience of the mother–daughter relationship and the effect on coping with diabetes in the context of life transitions.
Conclusions. Understanding the impact diabetes has on the emotional and social well being of both women with type 1 diabetes and their mothers is critical in planning appropriate support for both groups. Most importantly, it is critical to understand the guilt dynamic that operates during young women with diabetes' life transitions when the daughters' dependency on their mother's control and responsibility for diabetes management undergo changes resulting in emotional responses, especially guilt feelings.
Relevance to clinical practice. Health professionals need to understand the emotional and social impact of the guilt dynamics between young women with type 1 diabetes and their mothers. Adequate and appropriate support can minimize the guilt feelings and enhance stability and quality of life for both mothers and their daughters, especially during major life transitions, such as motherhood.