Big tau aggregation disrupts microtubule tyrosination and causes myocardial diastolic dysfunction: from discovery to therapy.

BACKGROUND: Amyloid plaques and neurofibrillary tangles, the molecular lesions that characterize Alzheimer's disease (AD) and other forms of dementia, are emerging as determinants of proteinopathies 'beyond the brain'. This study aims to establish tau's putative pathophysiological mechanistic roles and potential future therapeutic targeting of tau in heart failure (HF). METHODS AND RESULTS: A mouse model of tauopathy and human myocardial and brain tissue from patients with HF, AD, and controls was employed in this study. Tau protein expression was examined together with its distribution, and in vitro tau-related pathophysiological mechanisms were identified using a variety of biochemical, imaging, and functional approaches. A novel tau-targeting immunotherapy was tested to explore tau-targeted therapeutic potential in HF. Tau is expressed in normal and diseased human hearts, in contradistinction to the current oft-cited observation that tau is expressed specifically in the brain. Notably, the main cardiac isoform is high-molecular-weight (HMW) tau (also known as big tau), and hyperphosphorylated tau segregates in aggregates in HF and AD hearts. As previously described for amyloid-beta, the tauopathy phenotype in human myocardium is of diastolic dysfunction. Perturbation in the tubulin code, specifically a loss of tyrosinated microtubules, emerged as a potential mechanism of myocardial tauopathy. Monoclonal anti-tau antibody therapy improved myocardial function and clearance of toxic aggregates in mice, supporting tau as a potential target for novel HF immunotherapy. CONCLUSION: The study presents new mechanistic evidence and potential treatment for the brain-heart tauopathy axis in myocardial and brain degenerative diseases and ageing.

Palliative care research utilising intersectionality: a scoping review.

BACKGROUND: Access to palliative care is recognised as a human right, yet clear disparities exist. There have been recent appeals to examine people's contexts and interactions with social systems which for many, adversely influence their utilisation of palliative care. Intersectionality provides a way to understand these drivers of inequity and ultimately advocate for change. AIM: To identify and describe published studies utilising intersectionality in relation to need, access and experience of palliative care. DESIGN: A scoping review. DATA SOURCES: Medline, PsycINFO, CINAHL and Google Scholar databases and a manual search were undertaken for studies published up to January 2023. Included studies were evidence based articles where palliative or end of life care was the focus and intersectionality was identified and/or applied to the research that was undertaken. RESULTS: Ten published studies were included. An analytic framework was developed to identify the extent that intersectionality was utilised in each study. A wide range of different groups were researched across the studies, with most focusing on aspects of their participant's identity in relation to palliative care access and experience. Common topics of power, heterogeneity of people within the health system and barriers to palliative care were illuminated across the studies. CONCLUSIONS: Very limited research to date has utilised intersectionality to understand access, utilisation and experience of palliative care. This scoping review demonstrates intersectionality can provide a way to illuminate rich understandings of inequity in palliative care. It is imperative that future palliative research incorporates an intersectionality focus to further clarify the needs and experiences of structurally marginalised groups.

Be You: A national education initiative to support the mental health of Australian children and young people.

Early learning services and schools provide unique settings for mental health promotion and early intervention due to the potential for population-level dosage and reach in terms of reducing multiple risk factors and enabling protective factors among young people. Educators play a key role in supporting children and young people's experiences of, and access to mental health promotion opportunities, and hold unparalleled opportunity in terms of creating mental health-promoting learning environments. In 2018, the Australian National Mental Health in Education Initiative, Be You, was launched. Be You is a multi-million-dollar Australian government-supported initiative, freely available to all 24,000 early learning services, primary and secondary schools throughout Australia. The potential for subsequent population reach is proposed to potentially exceed that of any mental health promotion initiative for children and young people previously observed in Australia. Be You aims to foster mentally healthy learning communities across Australia through building capacity among educators to embed mental health promotion strategies. The Initiative was developed based on a review and integration of previous national mental health promotion frameworks, with an overall alignment to existing state and territory education, social and emotional well-being frameworks, and the Australian Curriculum. In delivering facilitated support from specialised consultants to early learning services and schools participating in the initiative, Be You draws on professional learning principles designed to build capacity in educators and educational systems relating to mental health promotion. It uses an updated, multi-module online platform providing interactive, evidence-based resources. This paper presents the Be You framework, describes the evidence sources used to inform the underlying principles and objectives, discusses the specific components that form the initiative, details the professional learning modules and content, and discusses potential implications for population mental health and prevention efforts.

The Positive and Negative Experiences of 342 Antidepressant Users.

Most efficacy and safety studies about medications adopt a quantitative approach, testing specific hypotheses with restricted samples. This online survey provides additional insights by directly asking people open questions. Thematic analysis was used to explore the responses of 342 antidepressant users to "Is there anything else you would like to tell us about your experience of taking medication". 59 (17.3%) made exclusively positive comments, 146 (42.7%) purely negative comments and 137 (40.0%) offered a mixture of positive and negative. Positive themes included: daily coping, life-changing/saving and stepping stone. Negative themes included: physical adverse effects, emotional and cognitive blunting, and withdrawal effects. Many participants also commented on relationships with prescribers. Collaboration was particularly valued. Negative sub-themes included failings in relation to information (especially about adverse effects and withdrawal), support, and alternatives. Clinicians have a duty to inform potential antidepressant users about positive and adverse effects, including withdrawal effects.

Replication of a whole school ethos-changing intervention: different context, similar effects, additional insights.

BACKGROUND: Whole school, ethos-changing interventions reduce risk behaviours in middle adolescence, more than curriculum-based approaches. Effects on older ages are not known. We set out to replicate one of these interventions, Australia's Gatehouse Project, in a rural Canadian high school. METHODS: A guided, whole school change process sought to make students feel more safe, connected, and valued by: changes in teaching practices, orientation processes, professional development of staff, recognition and reward mechanisms, elevating student voice, and strategies to involve greater proactivity and participation. We conducted risk behaviour surveys in grades 10 to 12 before the intervention and 2 years afterwards, and social network analyses with the staff. Changes in health and health risk behaviours were assessed using chi-square. Interactions between the intervention and gender and between the intervention and school engagement were assessed using interaction terms in logistic regression models. Changes in the density of relationships among staff were tested with methods analogous to paired t-tests. RESULTS: Like Gatehouse, there was no statistically significant reduction in depressive symptoms or bullying, though the trend was in that direction. Among girls, there was a statistically significant decrease in low school engagement (45% relative reduction), and decreases in drinking (46% relative reduction), unprotected sex (61% relative reduction) and poor health (relative reduction of 73%). The reduction in drinking matched the national trend. Reductions in unprotected sex and poor health went against the national trend. We found no statistically significant changes for boys. The effects coincided with statistically significant increases in the densities of staff networks, indicating that part of the mechanism may be through relationships at school. CONCLUSIONS: A non-specific, risk protective intervention in the social environment of the school had a significant impact on a cluster of risk behaviours for girls. Results were remarkably like reports from similar school environment interventions elsewhere, albeit with different behaviours being affected. It may be that this type of intervention activates change processes that interact highly with context, impacting different risks differently, according to the prevalence, salience and distribution of the risk and the interconnectivity of relationships between staff and students. This requires further exploration.

Causes of mortality and pathological lesions observed post-mortem in red squirrels (Sciurus vulgaris) in Great Britain.

BACKGROUND: The red squirrel population in Great Britain has declined dramatically in recent decades, principally due to squirrelpox. Concern exists that red squirrels may become extinct nationally and, as there has been limited research in to diseases other than squirrelpox, this study aimed to identify additional causes of mortality. RESULTS: Post-mortem examinations on 163 red squirrels found dead on Isle of Wight (IoW) England, in Scotland and at other locations in Great Britain showed that 41.7% (n = 68) were killed by road traffic and 9.2% (n = 15) by predators, principally domestic cats and dogs. The overall male/female ratio was 1.08/1. Fleas were recorded on 34.9% of IoW squirrels and on 43.8% of Scottish squirrels but sucking lice and ixodid ticks were only seen on Scottish squirrels. Bacterial infections were significant, particularly in association with respiratory disease (n = 16); two squirrels died of Bordetella bronchiseptica bronchopneumonia. Cases of fatal exudative dermatitis (n = 5) associated with a lukM-positive clone of Staphylococcus aureus occurred only on the IoW. Toxoplasmosis (n = 12) was also confined to IoW where it was responsible for almost one tenth (9.5%) of all deaths. Hepatozoonosis was common, especially in IoW squirrels, but was not considered a primary cause of mortality. Hepatic capillariasis affected four IoW squirrels and one from Scotland. Fungal infections included oral candidiasis, adiaspiromycosis and pulmonary phaeohyphomycosis. Neoplastic conditions diagnosed were: pulmonary carcinoma, gastric spindle cell tumour, renal papillary adenoma and trichoepithelioma. Epidermal hyperplasia of unknown aetiology was seen in squirrels showing crusty lesions of the ear pinnae on IoW (n = 3) and Brownsea Island (n = 1), associated in two cases with cutaneous wart-like growths. Miscellaneous diagnoses included chylothorax, electrocution, intussusception, suspected cholecalciferol rodenticide poisoning and foetal death and mummification. No cases of squirrelpox were diagnosed. CONCLUSIONS: Red squirrels in Britain suffer premature or unnatural mortality due to a number of conditions in addition to squirrelpox, many of which result, directly or indirectly, from human activities: road traffic trauma, pet predation, toxoplasmosis, trap injuries, rodenticide poisoning and electrocution accounted for 61% of all recorded mortality in this study. Red squirrels are also affected by several diseases of unknown aetiology which merit further research.

Are mental health nurses meeting the requirements of second health professionals in presenting opinions to the court?

WHAT IS KNOWN ON THE SUBJECT?: Mental health legislation is currently under review following recommendations for repeal and replacement. Through the statutory role of the second health professional, mental health nurses are in a strong position to offer a unique clinical perspective, engagement and advocacy for tangata whaiora (person seeking wellness) and whanau. Maori are more likely to be subject to a compulsory treatment order than non-Maori. Whanau involvement in care is a core element to well-being from a Te Ao Maori (Maori world view) perspective. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: Understanding the level of whanau involvement in the MHA process. Understanding challenges for nursing practice for consideration in the current review of MHA legislation. Identification of the opportunity nurses have to contribute to reducing high rates of Maori under CTOs. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The current MHA review needs to include the resourcing required to support the clinicians practising in statutory roles. More emphasis is needed to build the cultural knowledge and capability of the nursing workforce to integrate principles of a Te Ao Maori worldview into care delivery. These learnings highlight the importance of nursing responsibility in the SHP role. ABSTRACT: Introduction Clinical practice within statutory roles is an important issue for the nursing profession. There is increasing involvement of nurses undertaking statutory roles and opportunities for nurses to advocate and offer their unique clinical opinion regarding the need for restrictive measures imposed by mental health act legislation. Aim The aim of this study was to analyse whether registered nurses who undertake the role of second health professional (SHP) within New Zealand's Mental Health (Compulsory Assessment and Treatment) Act (1992) (MHA) are meeting the expectations of that role. Method A retrospective analysis of 156 cases was undertaken of clinical reports completed by registered nurses. The reports were measured against an established competency framework modified to include MHA expectations for whanau (family) involvement. Results From a sample of 156 cases, 22 were identified as reviews of initial orders for assessment and treatment while 134 were opinions related to the application for a compulsory treatment order (CTO). In most cases, reports achieved a good standard. There were limitations in nurses completing the documentation to the required standard, and adaptations were evident in efforts to meet clinical and legal expectations. There was a significant absence of evidence of whanau consultation. Discussion Resourcing through education, support and ongoing development are required to ensure that nurses are equipped to meet the expectations of the legislation. There is an opportunity for nurses to influence decision-making and support the reduction in use of community treatment orders. A review of the existing competency framework is required to include cultural approaches and involvement of whanau. Implications for Practice It is important to understand the factors that strengthen nursing practice to improve health outcomes and tangata whaiora and whanau experience. This study uses methods of clinical audit to describe current practice and establish an evidence base to measure change. It also offers important learnings for consideration within MHA legislation review and for nursing workforce development.

Fatal exudative dermatitis in island populations of red squirrels (Sciurus vulgaris): spillover of a virulent Staphylococcus aureus clone (ST49) from reservoir hosts.

Fatal exudative dermatitis (FED) is a significant cause of death of red squirrels (Sciurus vulgaris) on the island of Jersey in the Channel Islands where it is associated with a virulent clone of Staphylococcus aureus, ST49. S. aureus ST49 has been found in other hosts such as small mammals, pigs and humans, but the dynamics of carriage and disease of this clone, or any other lineage in red squirrels, is currently unknown. We used whole-genome sequencing to characterize 228 isolates from healthy red squirrels on Jersey, the Isle of Arran (Scotland) and Brownsea Island (England), from red squirrels showing signs of FED on Jersey and the Isle of Wight (England) and a small number of isolates from other hosts. S. aureus was frequently carried by red squirrels on the Isle of Arran with strains typically associated with small ruminants predominating. For the Brownsea carriage, S. aureus was less frequent and involved strains associated with birds, small ruminants and humans, while for the Jersey carriage S. aureus was rare but ST49 predominated in diseased squirrels. By combining our data with publicly available sequences, we show that the S. aureus carriage in red squirrels largely reflects frequent but facile acquisitions of strains carried by other hosts sharing their habitat ('spillover'), possibly including, in the case of ST188, humans. Genome-wide association analysis of the ruminant lineage ST133 revealed variants in a small number of mostly bacterial-cell-membrane-associated genes that were statistically associated with squirrel isolates from the Isle of Arran, raising the possibility of specific adaptation to red squirrels in this lineage. In contrast there is little evidence that ST49 is a common carriage isolate of red squirrels and infection from reservoir hosts such as bank voles or rats, is likely to be driving the emergence of FED in red squirrels.

Harnessing complexity: taking advantage of context and relationships in dissemination of school-based interventions.

Schools and school systems are increasingly asked to use evidence-based strategies to promote the health and well-being of students. The dissemination of school-based health promotion research, however, offers particular challenges to conventional approaches to dissemination. Schools and education systems are multifaceted organizations that sit within constantly shifting broader contexts. This article argues that health promotion dissemination needs to be rethought for school communities as complex systems and that this requires understanding and harnessing the dynamic ecology of the sociopolitical context. In developing this argument, the authors draw on their experience of the dissemination process of a multilevel school-based intervention in a complex educational context. Building on this experience, they argue for the need to move beyond conventional dissemination strategies to a focus on active partnerships between developers and users of school-based intervention research and offer a conceptual tool for planning dissemination.

The Heart of the Alzheimer's: A Mindful View of Heart Disease.

Purpose of Review: This review summarizes the current evidence for the involvement of proteotoxicity and protein quality control systems defects in diseases of the central nervous and cardiovascular systems. Specifically, it presents the commonalities between the pathophysiology of protein misfolding diseases in the heart and the brain. Recent Findings: The involvement of protein homeostasis dysfunction has been for long time investigated and accepted as one of the leading pathophysiological causes of neurodegenerative diseases. In cardiovascular diseases instead the mechanistic focus had been on the primary role of Ca2+ dishomeostasis, myofilament dysfunction as well as extracellular fibrosis, whereas no attention was given to misfolding of proteins as a pathogenetic mechanism. Instead, in the recent years, several contributions have shown protein aggregates in failing hearts similar to the ones found in the brain and increasing evidence have highlighted the crucial importance that proteotoxicity exerts via pre-amyloidogenic species in cardiovascular diseases as well as the prominent role of the cellular response to misfolded protein accumulation. As a result, proteotoxicity, unfolding protein response (UPR), and ubiquitin-proteasome system (UPS) have recently been investigated as potential key pathogenic pathways and therapeutic targets for heart disease. Summary: Overall, the current knowledge summarized in this review describes how the misfolding process in the brain parallels in the heart. Understanding the folding and unfolding mechanisms involved early through studies in the heart will provide new knowledge for neurodegenerative proteinopathies and may prepare the stage for targeted and personalized interventions.

QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data.

Array-based technologies have been used to detect chromosomal copy number changes (aneuploidies) in the human genome. Recent studies identified numerous copy number variants (CNV) and some are common polymorphisms that may contribute to disease susceptibility. We developed, and experimentally validated, a novel computational framework (QuantiSNP) for detecting regions of copy number variation from BeadArray SNP genotyping data using an Objective Bayes Hidden-Markov Model (OB-HMM). Objective Bayes measures are used to set certain hyperparameters in the priors using a novel re-sampling framework to calibrate the model to a fixed Type I (false positive) error rate. Other parameters are set via maximum marginal likelihood to prior training data of known structure. QuantiSNP provides probabilistic quantification of state classifications and significantly improves the accuracy of segmental aneuploidy identification and mapping, relative to existing analytical tools (Beadstudio, Illumina), as demonstrated by validation of breakpoint boundaries. QuantiSNP identified both novel and validated CNVs. QuantiSNP was developed using BeadArray SNP data but it can be adapted to other platforms and we believe that the OB-HMM framework has widespread applicability in genomic research. In conclusion, QuantiSNP is a novel algorithm for high-resolution CNV/aneuploidy detection with application to clinical genetics, cancer and disease association studies.

Staying on, and coming off, antidepressants: The experiences of 752 UK adults.

INTRODUCTION: Prescription rates for antidepressants (ADs) are high and continue to increase, despite evidence of significant adverse effects, including withdrawal symptoms, and marginal benefit relative to placebo only for short-term treatment of major depression. Such high rates seem to be explicable more in terms of long term usage and repeat prescribing rather than by increases in depression or new patients. METHOD: This paper reports the responses of a convenience sample of 752 people who had taken antidepressants, but no other psychiatric drugs, 'within the last two years' and completed the Medications for Mental Health Survey online in the UK. RESULTS: Most participants had either come off antidepressants (34%) or had tried and failed (36%). Of those still taking them 76% had been doing so for at least a year and 36% for five years or more. 26% expected to take them forever. About half (48%) did not have their drugs reviewed at least every three months. Most (65%) had never had a discussion with the prescriber about coming off. Nearly half (45%) of those who had stopped the drugs had done so without consulting their doctor. However, of those who came off after consulting their doctor, the majority (65%) experienced the doctor to be supportive. CONCLUSIONS: The findings are consistent with the idea that high rates are largely explicable by chronic usage, which in turn is partially explained by withdrawal symptoms. Prescribers should strive to establish collaborative relationships in which patients are fully informed about withdrawal effects and their views, about starting and finishing medication, should be explored and valued.

Pathogen invasion history elucidates contemporary host pathogen dynamics.

Amphibians, the most threatened group of vertebrates, are seen as indicators of the sixth mass extinction on earth. Thousands of species are threatened with extinction and many have been affected by an emerging infectious disease, chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd). However, amphibians exhibit different responses to the pathogen, such as survival and population persistence with infection, or mortality of individuals and complete population collapse after pathogen invasion. Multiple factors can affect host pathogen dynamics, yet few studies have provided a temporal view that encompasses both the epizootic phase (i.e. pathogen invasion and host collapse), and the transition to a more stable co-existence (i.e. recovery of infected host populations). In the Sierra Nevada mountains of California, USA, conspecific populations of frogs currently exhibit dramatically different host/ Bd-pathogen dynamics. To provide a temporal context by which present day dynamics may be better understood, we use a Bd qPCR assay to test 1165 amphibian specimens collected between 1900 and 2005. Our historical analyses reveal a pattern of pathogen invasion and eventual spread across the Sierra Nevada over the last century. Although we found a small number of Bd-infections prior to 1970, these showed no sign of spread or increase in infection prevalence over multiple decades. After the late 1970s, when mass die offs were first noted, our data show Bd as much more prevalent and more spatially spread out, suggesting epizootic spread. However, across the ~400km2 area, we found no evidence of a wave-like pattern, but instead discovered multiple, nearly-simultaneous invasions within regions. We found that Bd invaded and spread in the central Sierra Nevada (Yosemite National Park area) about four decades before it invaded and spread in the southern Sierra Nevada (Sequoia and Kings Canyon National Parks area), and suggest that the temporal pattern of pathogen invasion may help explain divergent contemporary host pathogen dynamics.

Conservation of genetic uniqueness in remaining populations of red squirrels (Sciurus vulgaris L.) in the South of England.

The Eurasian red squirrel (Sciurus vulgaris) is an emblematic species for conservation, and its decline in the British Isles exemplifies the impact that alien introductions can have on native ecosystems. Indeed, red squirrels in this region have declined dramatically over the last 60 years due to the spread of squirrelpox virus following the introduction of the gray squirrel (Sciurus carolinensis). Currently, red squirrel populations in Britain are fragmented and need to be closely monitored in order to assess their viability and the effectiveness of conservation efforts. The situation is even more dramatic in the South of England, where S. vulgaris survives only on islands (Brownsea Island, Furzey Island, and the Isle of Wight). Using the D-loop, we investigated the genetic diversity and putative ancestry of the squirrels from Southern England and compared them to a European dataset composed of 1,016 samples from 54 populations. We found that our three populations were more closely related to other squirrels from the British Isles than squirrels from Europe, showed low genetic diversity, and also harbored several private haplotypes. Our study demonstrates how genetically unique the Southern English populations are in comparison with squirrels from the continental European range. We report the presence of four private haplotypes, suggesting that these populations may potentially harbor distinct genetic lineages. Our results emphasize the importance of preserving these isolated red squirrel populations for the conservation of the species.

BeadArray-based genotyping.

There is a demand for technologies that allow the interrogation of large numbers of SNP polymorphisms, both in whole-genome panels and in smaller custom designed sets, to attempt to elucidate the nature of complex disease through linkage and association studies. The Illumina BeadArray technology offers a flexible platform for such analyses through two assays: GoldenGate, as described in this chapter, and Infinium II. Both assays utilize the BeadArray technology, where targeted regions of DNA are immobilized on beads randomly arranged into arrays, and the SNPs visualized through fluorescent tags, which differentiate among alleles. The platform is scalable such that mid- to high-throughput projects can be designed and completed in either a manual or automated mode. Small amounts of starting material are required, and in the case of GoldenGate, some level of sample degradation can be tolerated. The assays are efficient and reliable giving high pass rates and concordance levels.

Access to specialist palliative care services by people with severe and persistent mental illness: A retrospective cohort study.

Compared to the general population, people with pre-existing serious and persistent mental illness (SPMI) have higher rates of physical illness and die at an earlier age, raising questions about their palliative and end-of-life care needs when they are diagnosed with an incurable physical illness. In the present study, we explored access to specialist palliative care services within one New Zealand health district. Routinely-collected, de-identified patient information on a cohort of people diagnosed with SPMI, and receiving specialist palliative care services from the Capital and Coast District Health Board (CCDHB), was compared to the general population from the same health district. People with SPMI are 3.5 times less likely to receive specialist palliative services compared to the general population from the Capital and Coast District Health Board. The proportion of people identifying as Maori is 1.2 times higher in the SPMI cohort than the general CCDHB population. The SPMI cohort experiences a higher level of deprivation compared to the general population in the CCDHB. The present study confirms that those diagnosed with an SPMI are less likely to use specialist palliative care services at the end of life. Research using a national dataset is needed to determine whether the study findings are applicable to the national population.

A comparison of the Gatehouse Bullying Scale and the peer relations questionnaire for students in secondary school.

BACKGROUND: Bullying occurs in all schools. Measuring bullying in schools is complicated because both definitions of bullying and methods for measuring bullying vary. This study compared a brief 12-item Gatehouse Bullying Scale (GBS) with items drawn from the Peer Relations Questionnaire (PRQ), a well-established bullying questionnaire to measure the concurrent validity of the GBS. METHODS: Year 8 secondary school students (14 years of age) in metropolitan and regional Victoria, Australia, completed questionnaires assessing being teased, being deliberately left out, had rumors spread about oneself, and/or being physically threatened or hurt. RESULTS: The prevalence of bullying using GBS and PRQ was 57% and 61%, respectively. Percent agreement between the 2 measures was high. Agreement adjusted for chance was moderate (kappa 0.5). The GBS had good to moderate test-retest reliability (rho 0.65). CONCLUSIONS: The GBS is a short, reliable tool measuring the occurrence of bullying in schools. As well as a global estimate of bullying, the GBS provides estimates of 2 covert and 2 overt types of bullying which can be useful for schools to better plan interventions dealing with school bullying.

The interpersonal adverse effects reported by 1008 users of antidepressants; and the incremental impact of polypharmacy.

Antidepressant drugs are being prescribed at ever increasing rates internationally, despite marginal benefit compared to placebo and a range of adverse effects. Most studies of adverse effects focus on biological phenomena. This article presents the results of an online survey of 1008 self-selected anti-depressant users in Britain, which asked about five adverse effects in the interpersonal domain. The most commonly reported among participants who took only antidepressants were: Sex Life - 43.7%, Work or Study - 27.0% and Social Life - 23.5%. These rates of interpersonal adverse effects were even higher for the 52% of participants who were also taking one or more other psychiatric drugs. Only about a half (48%) felt they had been given enough information about side effects by the prescriber. Those initially prescribed medication by a psychiatrist were more likely to be on several types of drugs and reported more adverse effects than those whose prescriber was a General Practitioner (GP). Researchers and prescribers are encouraged to pay greater attention to interpersonal adverse effects.

Promoting social inclusion in schools: a group-randomized trial of effects on student health risk behavior and well-being.

OBJECTIVES: We sought to test the efficacy of an intervention that was designed to promote social inclusion and commitment to education, in reducing among students health risk behaviors and improving emotional well-being. METHODS: The design was a cluster-randomized trial in 25 secondary schools in Victoria, Australia. The subjects were 8th-grade students (aged 13 to 14 y) in 1997 (n=2545) and subsequent 8th-grade students in 1999 (n=2586) and 2001 (n=2463). The main outcomes were recent substance use, antisocial behavior, initiation of sexual intercourse, and depressive symptoms. RESULTS: At 4-year follow-up, the prevalence of marked health risk behaviors was approximately 20% in schools in the comparison group and 15% in schools in the intervention group, an overall reduction of 25%. In ordinal logistic regression models a protective effect of intervention was found for a composite measure of health risk behaviors in unadjusted models (odds ratio [OR]= 0.69; 95% confidence interval [CI]= 0.50, 0.95) and adjusted models (OR= 0.71; CI =0.52, 0.97) for potential confounders. There was no evidence of a reduction in depressive symptoms. CONCLUSION: The study provides support for prevention strategies in schools that move beyond health education to promoting positive social environments.

Seasonal variation in diagnosis of invasive cutaneous melanoma in Eastern England and Scotland.

BACKGROUND: Worldwide, the incidence of cutaneous melanoma has been reported to be highest in the summer and lowest in the winter. Northern Irish data suggested seasonal variation for women only, especially those with thinner melanomas, sited on limbs. We interrogated two larger UK cancer registries for temporal differences in melanoma diagnosis and associated patient characteristics. METHODS: Melanomas diagnosed from 2006 to 2010 in the Eastern England and Scottish cancer registries (n=11,611) were analysed by month of diagnosis, patient demographics and melanoma characteristics, using descriptive and multivariate modelling methods. RESULTS: More patients with melanoma were diagnosed in the summer months (June 9.9%, July 9.7%, August 9.8%) than the winter months (December 7.2%, January 7.2%, February 7.1%) and this pattern was consistent in both regions. There was evidence that the seasonal patterns varied by sex (p=0.015), melanoma thickness (p=0.002), body site (p=0.006), and type (superficial spreading melanomas p=0.005). The seasonal variation was greatest for diagnosis of melanomas occurring on the limbs. CONCLUSION: This study has confirmed seasonal variation in melanoma diagnosis in Eastern England and Scotland across almost all population demographics and melanoma characteristics studied, with higher numbers diagnosed in the summer months, particularly on the limbs. Seasonal patterns in skin awareness and related help-seeking are likely to be implicated. Targeted patient interventions to increase sun awareness and encourage year-long skin inspection are warranted.