Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Enhancing social functioning in young people at Ultra High Risk (UHR) for psychosis: A pilot study of a novel strengths and mindfulness-based online social therapy.

BACKGROUND: Psychological and pharmacological treatments have been shown to reduce rates of transition to psychosis in Ultra High Risk (UHR) young people. However, social functioning deficits have been unresponsive to current treatments. AIMS: The study aims were to: i) describe the theoretical basis and therapeutic targets of a novel intervention targeting social functioning in UHR young people; and ii) examine its acceptability, safety and preliminary effect on social functioning. METHODS: An international, multidisciplinary team developed a new intervention (MOMENTUM) to improve social functioning in UHR young people. MOMENTUM blends two novel approaches to social recovery: strengths and mindfulness-based intervention embedded within a social media environment, and application of the self-determination theory of motivation. The acceptability and safety of MOMENTUM were tested through a 2-month pilot study with 14 UHR participants. RESULTS: System usage was high, with over 70% of users being actively engaged over the trial. All participants reported a positive experience using MOMENTUM, considered it safe and would recommend it to others. 93% reported it to be helpful. There were large, reliable improvements in social functioning (d = 1.83, p < 0.001) and subjective wellbeing (d = 0.75, p = 0.03) at follow-up. There were significant increases in the mechanisms targeted by the intervention including strengths usage (d = 0.70, p = 0.03), mindfulness skills (d = 0.66, p = 0.04) and components of social support. Social functioning improvement was significantly correlated with indicators of system usage. CONCLUSION: MOMENTUM is engaging and safe. MOMENTUM appeared to engage the hypothesized mechanisms and showed promise as a new avenue to improve social functioning in UHR young people.

The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis.

BACKGROUND: When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. METHOD: We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. RESULTS: An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01-1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00-1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. CONCLUSIONS: There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.

Effect of narrowband ultraviolet B phototherapy on melanocytic naevi.

BACKGROUND: Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation. OBJECTIVES: To analyse changes in naevi exposed to NB-UVB in a large cohort of patients. METHODS: Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry. RESULTS: Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%). CONCLUSIONS: Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.

A comparative study of a 595-nm with a 585-nm pulsed dye laser in refractory port wine stains.

BACKGROUND: The pulsed dye laser (PDL) is the treatment of choice for port wine stains (PWS); however, some patients' PWS become refractory to further treatments. Technological advances have enabled new machines with the advent of surface cooling devices to deliver longer wavelengths and higher fluence more safely. These advances have the potential to achieve improved response rates in refractory PWS. There are few studies comparing the efficacy of standard PDL treatments for refractory PWS with the wider choice of treatment variables available from newer PDL machines. OBJECTIVES: To determine if there is any advantage of using a longer wavelength (595 nm) and pulse widths (1.5 ms, 6 ms and 20 ms) over conventional PDL settings (wavelength 585 nm, pulse width 1.5 ms) in refractory PWS. METHODS: Eighteen consecutive consenting patients with Fitzpatrick skin types 1-4 with a mean age 35 years (range 17-59 years) with refractory PWS were treated routinely with three separate test areas using 595-nm PDL (using three different pulse width settings of 1.5 ms, 6 ms and 20 ms), compared with test areas treated with 585-nm PDL (pulse width 1.5 ms). All test areas were treated with an identical fluence (15 J cm(-2)), spot size (7 mm) and cooling setting (dynamic cooling 60 ms, delay 60 ms). RESULTS: We found a statistically significant advantage of 595-nm PDL (pulse width 1.5 ms) over 595-nm PDL (pulse width 6 ms) (P < 0.05) in the treatment of refractory PWS; however, we found no significant advantage using longer pulse widths of 20 ms compared with 1.5 ms with the 595-nm PDL. There was no statistically significant advantage in using a 595-nm PDL over a 585-nm PDL using identical pulse widths of 1.5 ms, spot size, fluence and cryogen cooling settings; however, the number of directly comparable test areas was smaller. Some individual patients in our study obtained a better response with certain 595-nm PDL settings (pulse width 1.5 ms and 6 ms) compared with 585-nm PDL (pulse width 1.5 ms). CONCLUSIONS: Our experience of high fluence PDL in the treatment of refractory PWS suggests patients treated with 585 nm (pulse width 1.5 ms) improve to a similar degree as patients treated with 595-nm PDL (pulse width 1.5 ms). However, the use of the 595-nm PDL with longer pulse widths yields no extra advantage. For those patients who have failed to improve with high-fluence 585-nm PDL (pulse width 1.5 ms), test areas using 595-nm PDL (pulse width 1.5 ms and 6 ms) should be undertaken to ascertain if individual patients may benefit from the longer pulse width 595-nm PDL.

Evaluating complex, collaborative programmes: the Partnership Project as a case study.

OBJECTIVE: In Australia, mental health services are delivered by a complex web of public- and private-sector providers. There is a growing recognition that linkages between these groups are not optimal, and a concern that this may lead to poor outcomes. This paper illustrates a conceptual framework for developing, implementing and evaluating programmes concerned with linkages. METHOD: Drawing on theoretical and practical literature, this paper identifies different levels of integration, issues in evaluating programmes to address poor linkages, and features of useful evaluations. Within this context, it describes the method by which the Public and Private Partnerships in Mental Health Project (Partnership Project) is being evaluated. Conducted by St Vincent's Mental Health Service and The Melbourne Clinic, this is one of several Demonstration Projects in Integrated Mental Health Care funded under the National Mental Health Strategy. RESULTS: Collaboration is hard to conceptualize and collaborative programmes usually have many players and components, and tend to operate within already-complex systems. This creates difficulties for evaluation, in terms of what to measure, how to measure it, and how to interpret findings. In spite of these difficulties, the illustrative example demonstrates a model for evaluating collaborative programmes that is currently working well because it is strongly conceptualized, descriptive, comparative, constructively sceptical, positioned from the bottom up, and collaborative. CONCLUSIONS: This model, or aspects of it, could be extended to the evaluation of other mental health programmes and services that have collaborative elements.

Characterization of cellular pathways involved in glioblastoma response to the chemotherapeutic agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by gene expression profiling.

The effectiveness of chemotherapy for human cancers is limited by pharmacokinetic parameters such as variation in metabolism and is determined by the cellular response. In this work, we aimed to gain a more holistic understanding of the molecular basis of glioma response to the DNA-alkylating agent 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) by using a systematic approach: we investigated the expression of 588 genes with various cellular functions in a BCNU-resistant glioblastoma cell line and a BCNU-sensitive subline before and after treatment with BCNU. Our gene expression profiling revealed major differences in gene expression between these two cell lines, especially after treatment with BCNU. One striking example was that BCNU decreased the expression of six DNA-repair genes in sensitive but not in resistant cells. In sensitive cells, BCNU treatment resulted in the induction of two MAP kinase genes; this finding suggests that the specific response to BCNU in sensitive cells may involve the Jun kinase signal transduction pathway. After BCNU treatment, marked induction of tumor necrosis factor was detected only in sensitive cells, suggesting that tumor necrosis factor is a mediator of BCNU-induced cell death. Bcl-2 family members were not altered by BCNU in sensitive cells, suggesting that BCNU-induced cell death may be independent of the bcl-2 pathway. Results of the present study demonstrate that gene expression profiling may facilitate identification of cellular pathways associated with specific responses to chemotherapeutic agents and contribute to an understanding of the molecular basis of drug action.

Monitoring and care of young people at incipient risk of psychosis.

This article describes the theoretical background, origins, and development of a new clinical service for intervention in the putatively prodromal phase of schizophrenia and other psychotic disorders. Establishing such a service required examination of conceptual issues such as the meaning of the prodrome in psychosis and its association with risk of subsequent psychosis, and of practical issues related to identifying prodromal patients in the community and engaging them in monitoring and treatment. Patients' needs, timing, and mode of treatment had to be considered. Preliminary data from the service's 20-month pilot phase are presented to help inform these issues.