Brief psychological interventions for psychiatric disorders in young people with long term physical health conditions: A systematic review and meta-analysis.

OBJECTIVES: Rates of psychiatric disorders are considerably elevated in young people with long term physical health conditions. Currently few children obtain effective mental health treatments in the context of long term physical health conditions, and ways to improve access to evidence-based mental health interventions are urgently needed. One approach is to deploy briefer, more economical, yet still evidence-based, treatments. The objective of this review was to evaluate the efficacy of brief interventions targeting psychiatric disorders in children and young people with long term physical health conditions. METHODS: Predefined terms relating to brief psychological interventions for psychiatric disorders in children with long term physical health conditions were used to search relevant databases. A systematic review and meta-analysis was carried out in accordance with the Cochrane guidelines. Two reviewers independently screened titles and abstracts, extracted the data and conducted risk of bias assessments. RESULTS: A total of 12 randomised controlled trials were found to meet the inclusion criteria of the review. Of those, three studies were suitable for meta-analysis. A large effect size in favour of brief cognitive behavioural therapy for anxiety was found (g = - 0.95, CI -1.49 to -0.041; p < .001) with non-significant moderate-substantial heterogeneity (I2 = 58%; p = .09). CONCLUSION: This review suggests there is preliminary evidence that brief interventions, based on cognitive behavioural principles, may benefit young people with an anxiety disorder in the context of a long term physical health condition. There was insufficient evidence to assess whether this held true for depression and disruptive behaviour.

Demonstration of a CW diode-pumped Ar metastable laser operating at 4 W.

Optically pumped rare gas lasers are being investigated as potential high-energy, high beam quality systems. The lasing medium consists of rare gas atoms (Rg=Ne, Ar, Kr, or Xe) that have been electric discharge excited to the metastable np5(n+1)s P32 state. Following optical excitation, helium (He) at pressures of 200-1000 Torr is used as the energy transfer agent to create a population inversion. The primary technical difficulty for this scheme is the discharge production of sufficient Rg* metastables in the presence of >200 Torr of He. In this Letter, we describe a pulsed discharge that yields >1013 cm-3Ar* in the presence of He at total pressures up to 750 Torr. Using this discharge, a diode-pumped Ar* laser providing 4.1 W has been demonstrated.

Hierarchical Cluster Analysis of Three-Dimensional Reconstructions of Unbiased Sampled Microglia Shows not Continuous Morphological Changes from Stage 1 to 2 after Multiple Dengue Infections in Callithrix penicillata.

It is known that microglial morphology and function are related, but few studies have explored the subtleties of microglial morphological changes in response to specific pathogens. In the present report we quantitated microglia morphological changes in a monkey model of dengue disease with virus CNS invasion. To mimic multiple infections that usually occur in endemic areas, where higher dengue infection incidence and abundant mosquito vectors carrying different serotypes coexist, subjects received once a week subcutaneous injections of DENV3 (genotype III)-infected culture supernatant followed 24 h later by an injection of anti-DENV2 antibody. Control animals received either weekly anti-DENV2 antibodies, or no injections. Brain sections were immunolabeled for DENV3 antigens and IBA-1. Random and systematic microglial samples were taken from the polymorphic layer of dentate gyrus for 3-D reconstructions, where we found intense immunostaining for TNFα and DENV3 virus antigens. We submitted all bi- or multimodal morphological parameters of microglia to hierarchical cluster analysis and found two major morphological phenotypes designated types I and II. Compared to type I (stage 1), type II microglia were more complex; displaying higher number of nodes, processes and trees and larger surface area and volumes (stage 2). Type II microglia were found only in infected monkeys, whereas type I microglia was found in both control and infected subjects. Hierarchical cluster analysis of morphological parameters of 3-D reconstructions of random and systematic selected samples in control and ADE dengue infected monkeys suggests that microglia morphological changes from stage 1 to stage 2 may not be continuous.

Leptospira interrogans at the human-wildlife interface in northern Botswana: a newly identified public health threat.

Leptospirosis is the most widespread zoonosis in the world. In northern Botswana, humans live in close proximity to a diversity of wildlife and peridomestic rodents and may be exposed to a variety of zoonotic pathogens. Little is known regarding the occurrence and epidemiology of L. interrogans in Africa despite the recognized global importance of this zoonotic disease and the threat it poses to public health. In Botswana, banded mongooses (Mungos mungo) live in close proximity to humans across protected and unprotected landscapes and may be a useful sentinel species for assessing the occurrence of zoonotic organisms, such as L. interrogans. We utilized PCR to screen banded mongoose kidneys for leptospiral DNA and identified 41.5% prevalence of renal carriage of L. interrogans (exact binomial 95% CI 27.7-56.7%, n = 41). Renal carriage was also detected in one Selous' mongoose (Paracynictis selousi). This is the first published confirmation of carriage of L. interrogans in either species. This is also the first report of L. interrogans occurrence in northern Botswana and the only report of this organism in a wildlife host in the country. Pathogenic Leptospira are usually transmitted indirectly to humans through soil or water contaminated with infected urine. Other avenues, such as direct contact between humans and wildlife, as well as consumption of mongooses and other wildlife as bushmeat, may pose additional exposure risk and must be considered in public health management of this newly identified zoonotic disease threat. There is a critical need to characterize host species involvement and pathogen transmission dynamics, including human-wildlife interactions that may increase human exposure potential and infection risk. We recommend that public health strategy be modified to include sensitization of medical practitioners to the presence of L. interrogans in the region, the potential for human infection, and implementation of clinical screening. This study illustrates the need for increased focus on neglected zoonotic diseases as they present an important threat to public health.

Establishing a regional network of academic centers to support decision making for new vaccine introduction in Latin America and the Caribbean: the ProVac experience.

BACKGROUND: The Pan American Health Organization's ProVac Initiative, designed to strengthen national decision making regarding the introduction of new vaccines, was initiated in 2004. Central to realizing ProVac's vision of regional capacity building, the ProVac Network of Centers of Excellence (CoEs) was established in 2010 to provide research support to the ProVac Initiative, leveraging existing capacity at Latin American and Caribbean (LAC) universities. We describe the process of establishing the ProVac Network of CoEs and its initial outcomes and challenges. METHODS: A survey was sent to academic, not-for-profit institutions in LAC that had recently published work in the areas of clinical decision sciences and health economic analysis. Centers invited to join the Network were selected by an international committee on the basis of the survey results. Selection criteria included academic productivity in immunization-related work, team size and expertise, successful collaboration with governmental agencies and international organizations, and experience in training and education. The Network currently includes five academic institutions across LAC. RESULTS: Through open dialog and negotiation, specific projects were assigned to centers according to their areas of expertise. Collaboration among centers was highly encouraged. Faculty from ProVac's technical partners were assigned as focal points for each project. The resulting work led to the development and piloting of tools, methodological guides, and training materials that support countries in assessing existing evidence and generating new evidence on vaccine introduction. The evidence generated is shared with country-level decision makers and the scientific community. CONCLUSIONS: As the ProVac Initiative expands to other regions of the world with support from immunization and public health partners, the establishment of other regional and global networks of CoEs will be critical. The experience of LAC in creating the current network could benefit the formation of similar structures that support evidence-based decisions regarding new public health interventions.

Density functional theory (DFT) study of edaravone derivatives as antioxidants.

Quantum chemical calculations at the B3LYP/6-31G* level of theory were employed for the structure-activity relationship and prediction of the antioxidant activity of edaravone and structurally related derivatives using energy (E), ionization potential (IP), bond dissociation energy (BDE), and stabilization energies (ΔE(iso)). Spin density calculations were also performed for the proposed antioxidant activity mechanism. The electron abstraction is related to electron-donating groups (EDG) at position 3, decreasing the IP when compared to substitution at position 4. The hydrogen abstraction is related to electron-withdrawing groups (EDG) at position 4, decreasing the BDE(CH) when compared to other substitutions, resulting in a better antioxidant activity. The unpaired electron formed by the hydrogen abstraction from the C-H group of the pyrazole ring is localized at 2, 4, and 6 positions. The highest scavenging activity prediction is related to the lowest contribution at the carbon atom. The likely mechanism is related to hydrogen transfer. It was found that antioxidant activity depends on the presence of EDG at the C(2) and C(4) positions and there is a correlation between IP and BDE. Our results identified three different classes of new derivatives more potent than edaravone.

Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials.

Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine.

Physical mapping of immune genes in the tammar wallaby (Macropus eugenii).

The tammar wallaby (Macropus eugenii) is a model marsupial that has recently had its genome sequenced to a depth of 2-fold coverage. Although this is a great resource for comparative genomic studies, information on gene location is essential if this resource is to be used to its full potential. In this study, tammar wallaby bacterial artificial chromosomes (BACs) containing key immune genes were isolated from the tammar wallaby BAC library. BACs containing T cell receptor (TCR) and immunoglobulin (Ig) genes were physically mapped using fluorescence in situ hybridisation (FISH) to tammar wallaby chromosomes. Congruence between the locations of these immune genes in the tammar wallaby genome, with those predicted from chromosome painting data, highlights the conservation of genomic context of these important immune genes in marsupials. The isolation and mapping of these key immune genes in the tammar wallaby will aid in the assembly of the recently sequenced light coverage genome and assignment of sequence to chromosomes.

Predicting mortality for patients with exacerbations of COPD and Asthma in the COPD and Asthma Outcome Study (CAOS).

INTRODUCTION: Decisions about the intensity of treatment for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are influenced by predictions about survival and quality of life. Evidence suggests that these predictions are poorly calibrated and tend to be pessimistic. AIM: The aim of this study was to develop an outcome prediction model for COPD patients to support treatment decisions. METHODS: A prospective multi-centre cohort study in Intensive Care Units (ICU) and Respiratory High Dependency Units (RHDU) in the UK recruited patients aged 45 years and older admitted with an exacerbation of obstructive lung disease. Data were collected on patients' characteristics prior to ICU admission, and on their survival and quality of life after 180 days. An outcome prediction model was developed using multivariate logistic regression and bootstrapping. RESULTS: Ninety-two ICUs (53% of those in the UK) and three RHDUs took part. A total of 832 patients were recruited. Cumulative 180-day mortality was 37.9%. Using data available at the time of admission to the units, a prognostic model was developed which had an estimated area under the receiver operating characteristic curve ('c') of 74.7% after bootstrapping that was more discriminating than the clinicians (P = 0.033) and was well calibrated. DISCUSSION: This study has produced an outcome prediction model with slightly better discrimination and much better calibration than the participating clinicians. It has the potential to support risk adjustment and clinical decision making about admission to intensive care.

Survival and quality of life for patients with COPD or asthma admitted to intensive care in a UK multicentre cohort: the COPD and Asthma Outcome Study (CAOS).

BACKGROUND: Non-invasive ventilation is first-line treatment for patients with acutely decompensated chronic obstructive pulmonary disease (COPD), but endotracheal intubation, involving admission to an intensive care unit, may sometimes be required. Decisions to admit to an intensive care unit are commonly based on predicted survival and quality of life, but the information base for these decisions is limited and there is some evidence that clinicians tend to be pessimistic. This study examined the outcomes in patients with COPD admitted to the intensive care unit for decompensated type II respiratory failure. METHODS: A prospective cohort study was carried out in 92 intensive care units and 3 respiratory high dependency units in the UK. Patients aged 45 years and older with breathlessness, respiratory failure or change in mental status due to an exacerbation of COPD, asthma or a combination of the two were recruited. Outcomes included survival and quality of life at 180 days. RESULTS: Of the 832 patients recruited, 517 (62%) survived to 180 days. Of the survivors, 421 (81%) responded to a questionnaire. Of the respondents, 73% considered their quality of life to be the same as or better than it had been in the stable period before they were admitted, and 96% would choose similar treatment again. Function during the stable pre-admission period was a reasonable indicator of function reported by those who survived 180 days. CONCLUSIONS: Most patients with COPD who survive to 180 days after treatment in an intensive care unit have a heavy burden of symptoms, but almost all of them-including those who have been intubated-would want similar intensive care again under similar circumstances.

Preference for place of care and place of death in palliative care: are these different questions?

Place of death is at times suggested as an outcome for palliative care services. This study aimed to describe longitudinal preferences for place of care and place of death over time for patients and their caregivers. Longitudinal paired data of patient/caregiver dyads from a prospective unblinded cluster randomised control trial were used. Patients and caregivers were separately asked by the palliative care nurse their preference at that time for place of care and place of death. Longitudinal changes over time for both questions were mapped; patterns of agreement (patient and caregiver; and preference for place of death when last asked and actual placed of death) were analysed with kappa statistics. Seventy-one patient/caregiver dyads were analysed. In longitudinal preferences, preferences for both the place of care (asked a mean of >6 times) and place of death (asked a mean of >4 times) changed for patients (28% and 30% respectively) and caregivers (31% and 30%, respectively). In agreement between patients and caregivers, agreement between preference of place of care and preferred place of death when asked contemporaneously for patients and caregivers was low [56% (kappa 0.33) and 36% (kappa 0.35) respectively]. In preference versus actual place of death, preferences were met for 37.5% of participants for home death; 62.5% for hospital; 76.9% for hospice and 63.6% for aged care facility. This study suggests that there are two conversations: preference for current place of care and preference for care at the time of death. Place of care is not a euphemism for place of death; and further research is needed to delineate these. Patient and caregiver preferences may not change simultaneously. Implications of any mismatch between actual events and preferences need to be explored.

The impact of private-sector provision on equitable utilisation of coronary revascularisation in London.

OBJECTIVE: To investigate the impact of including private-sector data on assessments of equity of coronary revascularisation provision using NHS data only. DESIGN: Analyses of hospital episodes statistics and private-sector data by age, sex and primary care trust (PCT) of residence. For each PCT, the share of London's total population and revascularisations (all admissions, NHS-funded, and privately-funded admissions) were calculated. Gini coefficients were derived to provide an index of inequality across subpopulations, with parametric bootstrapping to estimate confidence intervals. SETTING: London. PARTICIPANTS: London residents undergoing coronary revascularisation April 2001-December 2003. INTERVENTION: Coronary artery bypass graft or angioplasty. MAIN OUTCOME MEASURES: Directly standardised revascularisation rates, Gini coefficients. RESULTS: NHS-funded age-standardised revascularisation rates varied from 95.2 to 193.9 per 100,000 and privately funded procedures from 7.6 to 57.6. Although the age distribution did not vary by funding, the proportion of revascularisations among women that were privately funded (11.0%) was lower than among men (17.0%). Privately funded rates were highest in PCTs with the lowest death rates (p = 0.053). NHS-funded admission rates were not related to deprivation nor age-standardised deaths rates from coronary heart disease. Privately funded admission rates were lower in more deprived PCTs. NHS provision was significantly more egalitarian (Gini coefficient 0.12) than the private sector (0.35). Including all procedures was significantly less equal (0.13) than NHS-funded care alone. CONCLUSION: Private provision exacerbates geographical inequalities. Those responsible for commissioning care for defined populations must have access to consistent data on provision of treatment wherever it takes place.

Transcription factor GATA-3 is involved in repression of promoter activity of the human interleukin-4 gene.

GATA-3 was shown to bind to two sites of the IL-4 gene promoter in human T-cell lines PER-117 and Jurkat. A motif located in the region of position -860 and responsible for GATA-3 binding was detected for the first time. Mutation or deletion of this site increased the promoter activity. The findings suggest a direct involvement of GATA-3 in regulation of the human IL-4 gene transcription as a repressor of the promoter activity.

Dexamethasone suppresses human interleukin-5 gene promoter.

Synthetic glucocorticoid dexamethasone suppressed interleukin-5 gene expression in PER-117 human T cells at the level of transcription. The conserved lymphokine element 0 in the interleukin-5 gene promoter context served as a target for dexamethasone.

An experimental study of determinants of the extent of disagreement within clinical guideline development groups.

OBJECTIVE: To assess the effect of design features and clinical and social cues on the extent of disagreement among participants in a formal consensus development process. METHODS: Factorial design involving 16 groups consisting of 135 general practitioners (GPs) and 42 mental health professionals from England. The groups rated the appropriateness of four mental health interventions for three conditions (chronic back pain, irritable bowel syndrome, and chronic fatigue syndrome) in the context of various clinical and social cues. The groups differed in three design features: provision of a systematic literature review (versus not provided), group composition (mixed versus GP only), and assumptions about the healthcare resources available (realistic versus idealistic). Disagreement was measured using the mean absolute deviation from a group's median rating for a scenario. RESULTS: None of the design features significantly affected the extent of disagreement within groups (all p>0.3). Disagreement did differ between treatments (closer consensus for cognitive behavioural therapy and behavioural therapy than for brief psychodynamic intervention therapy and antidepressants) and cues (closer consensus for depressed patients and patients willing to try any treatment). CONCLUSION: In terms of the extent of disagreement in the groups in this study, formal consensus development was a robust technique in that the results were not dependent on the way it was conducted.

Variation in the costs of delivering routine immunization services in Peru.

OBJECTIVE: Estimates of vaccination costs usually provide only point estimates at national level with no information on cost variation. In practice, however, such information is necessary for programme managers. This paper presents information on the variations in costs of delivering routine immunization services in three diverse districts of Peru: Ayacucho (a mountainous area), San Martin (a jungle area) and Lima (a coastal area). METHODS: We consider the impact of variability on predictions of cost and reflect on the likely impact on expected cost-effectiveness ratios, policy decisions and future research practice. All costs are in 2002 prices in US dollars and include the costs of providing vaccination services incurred by 19 government health facilities during the January-December 2002 financial year. Vaccine wastage rates have been estimated using stock records. FINDINGS: The cost per fully vaccinated child ranged from 16.63-24.52 U.S. Dollars in Ayacucho, 21.79-36.69 U.S. Dollars in San Martin and 9.58-20.31 U.S. Dollars in Lima. The volume of vaccines administered and wastage rates are determinants of the variation in costs of delivering routine immunization services. CONCLUSION: This study shows there is considerable variation in the costs of providing vaccines across geographical regions and different types of facilities. Information on how costs vary can be used as a basis from which to generalize to other settings and provide more accurate estimates for decision-makers who do not have disaggregated data on local costs. Future studies should include sufficiently large sample sizes and ensure that regions are carefully selected in order to maximize the interpretation of cost variation.

The parathyroid hormone-related protein receptor is expressed in breast cancer bone metastases and promotes autocrine proliferation in breast carcinoma cells.

Overproduction of parathyroid hormone-related protein (PTHRP) occurs in a high proportion of primary breast cancers (PBC) and is strongly implicated in their metastatic spread to bone. Although the PTHRP-receptor (PTHRP-R) is often coexpressed with PTHRP in PBC, its role in regulating breast cancer cell proliferation and metastases to bone remains unclear. The aims of this study were to determine the expression of the PTHRP-R in breast cancer bone metastases (BM) and to investigate the effects of PTHRP-R overexpression on breast cancer cell proliferation. PTHRP-R expression occurred in 85% (11 out of 13) of BM compared with 58% (39 out of 67) of PBC. Median expression was higher (P<0.05) in BM compared with PBC. PTHRP increased cAMP accumulation and DNA synthesis in MCF-7 cells stably overexpressing the PTHRP-R (MCF-7(WTR)) but not in MCF-7(VEC) control cells. The increase in DNA synthesis was mimicked by the cAMP pathway activator forskolin. The receptor antagonist PTHRP(7-34) reduced DNA synthesis in MCF-7(WTR) cells, but not MCF-7(VEC) cells, indicating that receptor overexpression promotes autocrine PTHRP activity. MCF-7(WTR) cells showed increased mitogenic responsiveness to fetal calf serum and reduced doubling times. PTHRP induced weak activation of ERK1 and ERK2 and potentiated their activation by serum growth factors. Collectively these results show that the PTHRP-R is frequently expressed in breast cancer BM and indicate that receptor overexpression drives proliferation via autocrine signals that are mediated via cAMP and ERK pathways.

Is postnatal depression a risk factor for sudden infant death?

BACKGROUND: In New Zealand, an association has been shown between postnatal depression and sudden infant death syndrome (SIDS). AIM: To replicate the New Zealand study. DESIGN OF STUDY: Case-control study. SETTING: The city of Sheffield, UK. METHOD: The database of the Sheffield Child Development Study was used Demographic and obstetric data were collected and at one month postpartum the Edinburgh Postnatal Depression Scale (EPDS) was administered. Detailed information on the cause of all infant deaths was available. RESULTS: There were 32,984 live births during the study period (from the year 1988 to 1993) and 42 babies died with the cause registered as SIDS. Multivariate analysis showed that smoking was the most important risk factorfor SIDS (odds ratio [OR] = 7.24, 95% confidence interval [95% CI] = 2.76 to 19.01), followed by a high EPDS (OR = 3.20, 95% CI = 1.46 to 6.99) and residence in an area of poverty (OR = 2.33, 95% CI = 1.06 to 5.11). CONCLUSIONS: The Sheffield data confirm the New Zealand findings. A high EPDS score and, by implication, postnatal depression, may be risk factors for SIDS, however, there are many possible explanations for the association.

Novel NG36/G9a gene products encoded within the human and mouse MHC class III regions.

Previous annotation of the Class III region of the human Major Histocompatibility Complex (MHC) depicts NG36 as an independent gene, which lies immediately centromeric to the G9a gene. However, data presented in this report show that in human and mouse cells the NG36 and G9a genes are predominantly expressed within a single approximately 3.9-kbp transcript. Thus, the human NG36/G9a gene contains 28 exons (4 exons from the NG36 gene and 24 exons from the G9a gene), spans 17.938 kb, and encodes a 1210-amino acid polypeptide. In addition, a splice variant (NG36G9a-SPI), which lacks exon 10, was found to be coexpressed together with the full-length NG36/G9a transcript in both human and mouse cells. To aid functional characterization of the novel NG36/G9a gene-product, T7-epitope-tagged versions of the complete NG36/G9a protein or the G9a region alone (amino acids 210 to 1210) was transiently expressed in mammalian cells. Surprisingly, the sub-cellular distribution of the NG36/G9a-T7 and G9a-T7 proteins was found to be quite distinct. Whereas the G9a-T7 protein was observed in both the cytoplasm and the nucleus, the NG36/G9a-T7 protein was extensively concentrated within the nucleus. Also, the G9a-T7 protein frequently appeared marginalized at the nuclear periphery, while the NG36/G9a-T7 protein was generally found throughout the nucleoplasm. As such, it would appear that the NG36 domain plays a key role in controlling the sub-cellular distribution of the NG36/G9a protein.