Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective: To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to 'current practice'. Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria ('equity'; 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6-17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios. Results: Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders. Conclusions: Cognitive behavioural therapy provided by a public psychologist is the most effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require 'start-up' costs and attention to ensuring an adequate workforce.

Variable effects of larval size on post-metamorphic performance in the field

Larval quality may be capable of explaining much of the variation in the recruitment and subsequent population dynamics of benthic marine invertebrates. Whilst the effects of larval nutritional condition on adult performance have received the most attention, recent work has shown that larval size may also be an important and ubiquitous source of variation in larval quality. We examined the effects of variation in larval size on the post-metamorphic survival and growth of Watersipora subtorquata in 2 very different habitats - experimental substrata and pier pilings. We found strong effects of larval size on colony performance, although these varied among experiments. For colonies on experimental substrata, larval size positively affected adult survival and, initially, growth. However, after 3 wk in the field, there was no relationship between larval size and colony size, possibly because colonies were completely surrounded by newly settled organisms. Larval size also positively affected post-metamorphic growth of colonies on pier pilings, but, surprisingly, colonies that came from larger larvae had lower survival than colonies from smaller larvae. Overall, variation in larval size will strongly affect the recruitment and subsequent performance of adults in this species, although this may vary among different habitats. This study highlights the importance of examining the effects of larval quality on adult performance in as realistic conditions as possible, because of the strong interaction between larval size effects and the environment.

Geographical variation in offspring size effects across generations

Offspring size is thought to strongly affect offspring fitness and many studies have shown strong offspring size/fitness relationships in marine and terrestrial organisms. This relationship is strongly mitigated by local environmental conditions and the optimal offspring size that mothers should produce will vary among different environments. It is assumed that offspring size will consistently affect the same traits among populations but this assumption has not been tested. Here I use a common garden experiment to examine the effects of offspring size on subsequent performance for the marine bryozoan Bugula neritina using larvae from two very different populations. The local conditions at one population (Williamstown) favour early reproduction whereas the other population (Pt. Wilson) favours early growth. Despite being placed in the same habitat, the effects of parental larval size were extremely variable and crossed generations. For larvae from Williamstown, parental larval size positively affected initial colony growth and larval size in the next generation. For larvae from the other population, parental larval size positively affected colony fecundity and negatively affected larval size in the next generation. Traditionally, exogenous factors have been viewed as the sole source of variation in offspring size/fitness relationship but these results show that endogenous factors (maternal source population) can also cause variation in this crucial relationship. It appears offspring size effects can be highly variable among populations and organisms can adapt to local conditions without changing the size of their offspring.

Age-at-first-registration for affective psychosis and schizophrenia

We compared the age-at-first-registration for patients with schizophrenia and affective psychosis in a statewide mental health register. After excluding those receiving (1) a diagnosis of both schizophrenia (ICD-9 295.x) and affective psychosis (ICD-9 296.x), or (2) a diagnosis of ICD-9 296.1 (which can cover major depressive episode), we adjusted the distributions for the age structure of the background general population. We found that all distributions showed a wide age range of onset, with a similar male modal age group of 20-24 for schizophrenia and 25-29 for affective psychosis. The female modal age group was 50-54 for both diagnoses. Although more individuals were diagnosed with schizophrenia (males = 2,434, females = 1,609) than with affective psychosis (males = 670, females = 913), the shape of the two distributions was similar. This finding suggests that factors influencing age-at-first-registration for schizophrenia and affective psychosis may be similar, especially for females.

Offspring size effects in the marine environment: A field test for a colonial invertebrate

A central tenet of life-history theory is the presence of a trade-off between the size and number of offspring that a female can produce for a given clutch. A crucial assumption of this trade-off is that larger offspring perform better than smaller offspring. Despite the importance of this assumption empirical, field-based tests are rare, especially for marine organisms. We tested this assumption for the marine invertebrate, Diplosoma listerianum, a colonial ascidian that commonly occurs in temperate marine communities. Colonies that came from larger larvae had larger feeding structures than colonies that came from smaller larvae. Colonies that came from larger larvae also had higher survival and growth after 2 weeks in the field than colonies that came from smaller larvae. However, after 3 weeks in the field the colonies began to fragment and we could not detect an effect of larval size. We suggest that offspring size can have strong effects on the initial recruitment of D. listerianum but because of the tendency of this species to fragment, offspring size effects are less persistent in this species than in others.

Transgenerational offspring size effects in marine invertebrates

In marine invertebrates, the larval and adult stages of many species are often ecologically distinct and as consequence these stages have been traditionally been viewed as physiologically separate. More recently, we have begun to recognize that metamorphosis does not represent a new beginning and events during the larval stage can influence adult performance. I will discuss recent work that suggests that the links between life-history stages are even more pervasive than we currently appreciate. For several species of marine invertebrate, I have found that events during one generation can strongly affect performance in the subsequent generation and events during the haploid phase can affect performance in the diploid phase. All of these links are mediated by changes in offspring size or offspring quality. I will discuss the implication of these strong links for the way we view the ecology of marine invertebrates and the evolution of offspring size in this group.

Less inhibited with age? Larval age modifies responses to natural settlement inhibitors

As larvae of marine invertebrates age, their response to settlement cues can change. This change can have significant consequences to both the ecology of these organisms, and to their response to antifouling coatings. This study examines how larval age affects the settlement response of larvae to two naturally derived settlement inhibitors, non-polar extracts from the algae Delisea pulchra and Dilophus marginatus, the former of which contains compounds that are in commercial development as antifoulants. Two species of marine invertebrates with non-feeding larvae were investigated: the bryozoans Watersipora subtorquata and Bugula neritina. Larval age strongly affected larval settlement, with older larvae settling at much higher rates than younger larvae. Despite having strong, inhibitory effects on young larvae, the non-polar extracts did not inhibit the settlement of older larvae to the same degree for both species studied. The results show that the effects of ecologically realistic settlement inhibitors are highly dependent on larval age. Given that the age of settling larvae is likely to be variable in the field, such age specific variation in settlement response of larvae may have important consequences for host-epibiont interactions in natural communities.

The usefulness of acetic acid wash and chemiluminescent illumination (Vizilite) in the visualization of oral mucosal white lesions

A diligent and careful examination of the mouth and oral structures has been historically deficient in revealing premalignant and malignant oral lesions. Conventional screening practice for oral neoplastic lesions involves visual scrutiny of the oral tissues with the naked eye under projected incandescent or halogen illumination. Visualization is the principal strategy used to find patients with lesions at risk for malignant transformation; hence, any procedure which highlights neoplastic lesions should aid the clinician. This pilot study examined the usefulness of acetic acid wash and chemiluminescent light (Vizilite) in enhancing visualization of oral mucosal white lesions, and its ability to highlight malignant and potentially malignant lesions. Fifty five patients referred for assessment of a white lesion, were prospectively screened with Vizilite, and an incisional biopsy performed for a definitive diagnosis. The age, sex, and smoking status of all patients were recorded, and all lesions were photographed. The visibility, location, size, border, and presence of satellite lesions, were also recorded. The Vizilite tool enhanced intraoral visualization of 26 white lesions, but it could not distinguish between epithelial hyperplasia, dysplasia, or carcinoma. Indeed, all lesions appeared ‘‘aceto-white’’, regardless of the definitive diagnosis. On one occasion, Vizilite aided in the identification of a satellite lesion that was not observed by routine visual inspection. Vizilite appears to be a useful visualization tool, but it does not aid in the identification of malignant and potentially malignant lesions of the oral mucosa.

Cognitive deficits, length of illness and symptom severity in schizophrenia

Background Research using neuropsychological testing has demonstrated that patients with schizophrenia show deficits in multiple neurocognitive domains. The aim of this study is to identify cognitive deficits that correlate with length of illness and symptom severity. Method Twenty clinically stable outpatients with chronic schizophrenia (18M : 2F) and 14 healthy controls (13M : 1F), matched on age, gender and parental education, were administered a neuropsychological battery consisting of the Hayling Sentence Completion Test (HSCT), WMS-III Verbal Paired Associates & Letter Number Sequencing, Modified Card Sort Test (MCST), Pyramids & Palm Trees Test, National Adult Reading Test (NART), Controlled Oral Word Association Test (COWAT), and WAIS-III. Severity of symptoms was rated with the Structured Clinical Interview – Positive and Negative Syndromes Scale (SCI-PANSS). Results In comparison to controls, patients showed significant deficits on all of the neuropsychological tasks except for the COWAT. MCST total categories, NART, Verbal IQ and arithmetic, similarities & digit symbol of the WAIS-III had the largest effect size between the groups. The longer the illness duration, the poorer the performance on WAISIII block design and the lower the performance IQ score. The poorer the performance on WMS-III letter number sequencing, the greater the positive symptoms, negative symptoms and general psychopathology. Conclusion Compared to controls, patients showed large effect sizes on measures of executive functioning, intelligence, working memory, verbal comprehension and speed of processing. The findings suggest that impairment in executive functioning and performance IQ is associated with length of illness, while impairment in working memory is associated with heightened symptom severity.

A comparison of dissected follicle numbers and follicle counts on the ovarian surface for the evaluation of ovarian follicular populations in Bos indicus cows

Ovaries (n = 140) from 70 mixed-age multiparous, lactating Brahman cross (3/4-7/8 Bos indicus) cows were used to examine the hypothesis that counts of follicles visible on the surface of the ovaries of Bos indicus cows and their classification into diameter size classes, are closely correlated with numbers of follicles in those size classes found by complete dissection of the ovary. immediately after ovariectomy, mean diameters (long and short axes averaged) of all follicles greater than or equal to 2 mm visible on the surface of each ovary were measured. All follicles greater than or equal to 2 mm were dissected from the ovaries, excess stroma removed and follicle diameters measured under a stereomicroscope using an ocular graticule. For each ovary, follicles were classified in either small (8 mm) categories based on either diameters of surface or dissected follicles. Data for numbers of surface and dissected follicles (mean +/- SE) in small, medium, large categories and total follicle numbers, respectively, were 24.4 +/- 1.6 vs. 28.0 +/- 1.9, 1.6 +/- + 0.2 vs. 11.6 +/- 1.0, 0.5 +/- 0.1 vs. 0.7 +/- 0.1 and 26.4 +/- 1.6 vs. 40.4 +/- 2.5. Correlation coefficients (r) for counts of surface and dissected follicles in small, medium, large and total follicle numbers were 0.76, 0.40, 0.69 and 0.79, respectively. Medium size follicles presented only a small translucent area on the surface of the ovary, leading to an underestimate of numbers when categorised by surface evaluation. Counts of follicles visible on the surface of the ovaries of Bos indicus cows and their classification into size classes based on estimated diameter, are closely correlated with numbers of follicles in those size classes found at dissection of the ovary for small (8 mm) and total follicles but not for medium sized (4-8 mm) follicles. (C) 1997 Elsevier Science B.V.

Cumulative sedimentation analysis of Escherichia coli debris size

A new method to measure Escherichia coil cell debris size after homogenization is presented. It is based on cumulative sedimentation analysis under centrifugal force, coupled with Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis of sedimented proteins. The effects that fermentation and homogenization conditions have on the resulting debris distributions were investigated using this method. Median debris size decreased significantly from approximately 0.5 mu m to 0.3 mu m as the number of homogenization passes increased from 2 to 10. Under identical homogenization conditions, uninduced host cells in stationary phase had a larger debris size than exponential cells after 5 homogenizer passes. This difference was not evident after 2 or in passes, possibly because of confounding intact cells and the existence of a minimum debris size for the conditions investigated. Recombinant cells containing protein inclusion bodies had the smallest debris size following homogenization. The method was also used to measure the size distribution of inclusion bodies. This result compared extremely well with an independent determination using centrifugal disc photosedimentation (CDS), thus validating the method. This is the first method that provides accurate size distributions of E. coli debris without the need for sample pretreatment, theoretical approximations (e.g. extinction coefficients), or the separation of debris and inclusion bodies prior to analysis. (C) 1997 John Wiley & Sons, Inc.