Treatment resistors

Treatment resistors, that is children whose reading skills have not responded to sustained periods of appropriate intervention, have long been the concern of parents, educators, clinicians and researchers. Rudolph Flesch's book of 1955, Why Johnny Can't Read and What You Can Do About It, sparked the "great (and largely continuing) debate" about appropriate instructional methods for teaching reading.

The PG500 series : novel heparan sulfate mimetics as potent angiogenesis and heparanase inhibitors for cancer therapy

Heparan sulfate mimetics, which we have called the PG500 series, have been developed to target the inhibition of both angiogenesis and heparanase activity. This series extends the technology underpinning PI-88, a mixture of highly sulfated oligosaccharides which reached Phase III clinical development for hepatocellular carcinoma. Advances in the chemistry of the PG500 series provide numerous advantages over PI-88. These new compounds are fully sulfated, single entity oligosaccharides attached to a lipophilic moiety, which have been optimized for drug development. The rational design of these compounds has led to vast improvements in potency compared to PI-88, based on in vitro angiogenesis assays and in vivo tumor models. Based on these and other data, PG545 has been selected as the lead clinical candidate for oncology and is currently undergoing formal preclinical development as a novel treatment for advanced cancer.

Nutritional status and information needs of medical oncology patients receiving treatment at an Australian public hospital

This study aimed to identify: i) the prevalence of malnutrition according to the scored Patient Generated-Subjective Global Assessment (PG-SGA); ii) utilization of available nutrition resources; iii) patient nutrition information needs; and iv) external sources of nutrition information. An observational, cross-sectional study was undertaken at an Australian public hospital on 191 patients receiving oncology services. According to PG-SGA, 49% of patients were malnourished and 46% required improved symptom management and/or nutrition intervention. Commonly reported nutrition-impact symptoms included: peculiar tastes (31%), no appetite (24%) and nausea (24%). External sources of nutrition information were accessed by 37%, with popular choices being media/internet (n=19) and family/friends (n=13). In a sub-sample (n=65), 32 patients were aware of the available nutrition resources, 23 thought the information sufficient and 19 patients had actually read them. Additional information on supplements and modifying side effects was requested by 26 patients. Malnutrition is common in oncology patients receiving treatment at an Australian public hospital and almost half require improved symptom management and/or nutrition intervention. Patients who read the available nutrition information found it useful, however awareness of these nutrition resources and the provision of information on supplementation and managing symptoms requires attention.

Tests of the elaborated intrusion theory of craving and desire : features of alcohol craving during treatment for an alcohol disorder

Objectives. We tested predictions from the elaborated intrusion (EI) theory of desire, which distinguishes intrusive thoughts and elaborations, and emphasizes the importance of imagery. Secondarily, we undertook preliminary evaluations of the Alcohol Craving Experience (ACE) questionnaire, a new measure based on EI Theory. Methods. Participants (N ¼ 232) were in correspondence-based treatment trials for alcohol abuse or dependence. The study used retrospective reports obtained early in treatment using the ACE, and daily self-monitoring of urges, craving, mood and alcohol consumption. Results. The ACE displayed high internal consistency and test – retest reliability and sound relationships with self-monitored craving, and was related to Baseline alcohol dependence, but not to consumption. Imagery during craving was experienced by 81%,with 2.3 senses involved on average. More frequent imagery was associated with longer episode durations and stronger craving. Transient intrusive thoughts were reported by 87% of respondents, and were more common if they frequently attempted to stop alcohol cognitions. Associations between average daily craving and weekly consumption were seen. Depression and negative mood were associated with more frequent, stronger and longer lasting desires for alcohol. Conclusions. Results supported the distinction of automatic and controlled processes in craving, together with the importance of craving imagery. They were also consistent with prediction of consumption from cross-situational averages of craving, and with positive associations between craving and negative mood. However, this study’s retrospective reporting and correlational design require that its results be interpreted cautiously. Research using ecological momentary measures and laboratory manipulations is needed before confident inferences about causality can be made.

Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum

Objectives: To report on the design, significance and potential impacts of the first documented human clinical trial assessing the anxiolytic and thymoleptic efficacy of an aqueous monoextract of Piper methysticum (kava). The significance of the qualitative element of our clinical trial is also explored. The Kava Anxiety Depression Spectrum Study (KADSS) is a 3-week placebocontrolled, double-blind, cross-over trial involving 60 adult participants (18—65) with elevated stable anxiety and varying levels of depressive symptoms. Aims: The aims of KADSS are: (1) to determine whether an aqueous standardised extract of kava is effective for the treatment of anxiety; (2) to assess the effects of kava on differing levels of depression; and (3) to explore participants’ experience of taking kava via qualitative research. The study also provides preliminary assessment of the safety of an aqueous extract of kava in humans. Conclusion: If results reveal that the aqueous kava preparation exerts significant anxiolytic effects and appears safe, potentially beneficial impacts may occur. Data supporting a safe and effective kava extract may encourage a re-introduction of kava to Europe, UK and Canada. This may provide a major socioeconomic benefit to Pacific Island nations, and to sufferers of anxiety disorders.

Mailed treatment to augment primary care for alcohol disorders : a randomised controlled trial

Introduction and Aims: Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods: A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3–6. Results: Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions: The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.

Psychological treatment dropout among pathological gamblers

Premature dropout from treatments for pathological gambling is potentially of significant importance, if it occurs before substantial progress has been made in addressing the problem. A systematic review of current research on dropout from psychological treatments for pathological gambling identified 12 studies from five countries. Dropout ranged from 14% to 50%, with a median of dropout 26%. Overall, 31% of the participants dropped out of treatment. Few studies distinguish between dropouts at different stages of participation. The evidence on specific variables that predict dropout is limited or inconsistent, and is characterised by a lack of a coherent, gambling-specific model and by methodological problems. Two studies that attempted to apply motivational and compliance-enhancing techniques were found. Both showed promising effects on reduction of dropout and improvement of short-term impact of treatment, but inconsistent results on longer-term outcomes were obtained. The review highlighted a need for more rigorous investigation of the extent of dropout and of variables associated with dropout from pathological gambling treatment programs. Further research on interventions to enhance retention and reduce dropout from psychological treatment is also required.

Ethyl-eicosapentaenoic acid in first-episode psychosis : a 1H-MRS study

Ethyl-eicosapentaenoic acid (E-EPA) is an omega-3 fatty acid that has been used in a range of neuropsychiatric conditions with some benefits. However, its mechanism of action is unknown. Here, we investigate its effects on in vivo brain metabolism in first-episode psychosis (FEP). Proton magnetic resonance spectroscopy at 3 T was performed in the temporal lobes of 24 FEP patients before and after 12 weeks of treatment in the context of a larger double-blind, placebo-controlled E-EPA augmentation study. Treatment group effects for glutathione (F1,12=6.1, p=0.03), and a hemisphere-by-group interaction for glutamine/glutamate (F1,20=4.4, p=0.049) were found. Glutathione increased bilaterally and glutamate/glutamine increased in the left hemisphere following E-EPA administration. Improvement in negative symptoms correlated with metabolic brain changes, particularly glutathione (r=-0.57). These results suggest that E-EPA augmentation alters glutathione availability and modulates the glutamine/glutamate cycle in early psychosis, with some of the metabolic brain changes being correlated with negative symptom improvement. Larger confirmatory studies of these postulated metabolic brain effects of E-EPA are warranted.

A 1H-MRS investigation of the medial temporal lobe in antipsychotic-naïve and early-treated first episode psychosis

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

Synthesis and characterization of boehmite nanofibers

Boehmite nanofibers of high quality were synthesized through a wet-gel conversion process without the use of a surfactant. The long nanofibers of boehmite with clear-cut edges were obtained by steaming the wet-gel precipitate at 170 ºC for 2 days under a pH 5. Hydrothermal treatment of the boehmite gels enabled self-assembly through directed crystal growth. Detailed characterization using X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Infrared Emission Spectroscopy (IES) and Raman Spectroscopy is presented.

Mechanisms of improvement in treatment for depression : test of a self-efficacy and performance model

Tested D. J. Kavanagh's (1983) depression model's explanation of response to cognitive-behavioral treatment among 19 20–60 yr old Ss who received treatment and 24 age-matched Ss who were assigned to a waiting list. Measures included the Beck Depression Inventory and self-efficacy (SE) and self-monitoring scales. Rises in SE and self-monitored performance of targeted skills were closely associated with the improved depression scores of treated Ss. Improvements in the depression of waiting list Ss occurred through random, uncontrolled events rather than via a systematic increase in specific skills targeted in treatment. SE regarding assertion also predicted depression scores over a 12-wk follow-up.

Effectiveness of current treatment approaches for benzodiazepine discontinuation : a meta-analysis.

Aims: To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation. Methods: A systematic review of approaches to benzodiazepine discontinuation in general practice and out-patient settings was undertaken. Routine care was compared with three treatment approaches: brief interventions, gradual dose reduction (GDR) and psychological interventions. GDR was compared with GDR plus psychological interventions or substitutive pharmacotherapies. Results: Inclusion criteria were met by 24 studies, and a further eight were identified by future search. GDR [odds ratio (OR) = 5.96, confidence interval (CI) = 2.08–17.11] and brief interventions (OR = 4.37, CI = 2.28–8.40) provided superior cessation rates at post-treatment to routine care. Psychological treatment plus GDR were superior to both routine care (OR = 3.38, CI = 1.86–6.12) and GDR alone (OR = 1.82, CI = 1.25–2.67). However, substitutive pharmacotherapies did not add to the impact of GDR (OR = 1.30, CI = 0.97– 1.73), and abrupt substitution of benzodiazepines by other pharmacotherapy was less effective than GDR alone (OR = 0.30, CI = 0.14–0.64). Few studies on any technique had significantly greater benzodiazepine discontinuation than controls at follow-up. Conclusions: Providing an intervention is more effective than routine care. Psychological interventions may improve discontinuation above GDR alone. While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use.

Substance Treatment Options in Psychosis (STOP) : a new intervention for dual diagnosis

Despite the high co-occurrence of psychosis and substance abuse, there is very little research on the development of effective treatments for this problem. This paper describes a new intervention that facilitates reaching functional goals through collaboration between therapists, participants and families. Substance Treatment Options in Psychosis (STOP) integrates pharmacological and psycho-logical treatments for psychotic symptoms, with cognitive-behavioural approaches to substance abuse. STOP is tailored to participants' problems and abilities, and recognises that control of consumption and even engagement may take several attempts. Training in relevant skills is augmented by bibliotherapy, social support and environmental change. A case description illustrates the issues and challenges in implementation.

Eye-movements and visual imagery : a working memory approach to the treatment of post-traumatic stress disorder

It has been claimed that the symptoms of post-traumatic stress disorder (PTSD) can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R), a procedure that involves the individual making saccadic eye-movements while imagining the traumatic event. We hypothesized that these eye-movements reduce the vividness of distressing images by disrupting the function of the visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce the intensity of the emotion associated with the image. This hypothesis was tested by asking non-PTSD participants to form images of neutral and negative pictures under dual task conditions. Their images were less vivid with concurrent eye-movements and with a concurrent spatial tapping task that did not involve eye-movements. In the first three experiments, these secondary tasks did not consistently affect participants' emotional responses to the images. However, Expt 4 used personal recollections as stimuli for the imagery task, and demonstrated a significant reduction in emotional response under the same dual task conditions. These results suggest that, if EMD-R works, it does so by reducing the vividness and emotiveness of traumatic images via the VSSP of working memory. Other visuospatial tasks may also be of therapeutic value.