Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial

Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease.

Pre-intravitrael injection preparation: endophthalmitis prevention and the importance of povidone-iodine

Despite adherence to strict standards of care in preparation for intravitreal injections, endophthalmitis can still occur. This article focuses on endophthalmitis and the importance of povidone-iodine in pre-procedure antisepsis. An overview of endophthalmitis and an examination of the benefits of povidone-iodine in ocular aseptic technique for the prevention of post-procedure endophthalmitis are provided. The misconceptions that patients and health practitioners may have in relation to povidone-iodine hypersensitivity are also explored.

An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): Protocol for a randomized controlled trial

Background

Organ dysfunction consequent to infection (‘severe sepsis’) is the leading cause of admission to an intensive care unit (ICU). In both animal models and early clinical studies the calcium channel sensitizer levosimendan has been demonstrated to have potentially beneficial effects on organ function. The aims of the Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS) trial are to identify whether a 24-hour infusion of levosimendan will improve organ dysfunction in adults who have septic shock and to establish the safety profile of levosimendan in this group of patients.

This is a multicenter, randomized, double-blind, parallel group, placebo-controlled trial. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg^-1.min^-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom.

This trial will test the efficacy of levosimendan to reduce acute organ dysfunction in adult patients who have septic shock and evaluate its biological mechanisms of action.

The impact of patient suicide on community mental health teams

Suicide in Scotland is considered an urgent public health issue affecting all aspects of society. The aim of this study was to explore how a patient suicide impacts on members of a community mental health team (CMHT). Six members of one CMHT were interviewed on two occasions, approximately nine months following a patient suicide. An interpretative descriptive model, drawing on elements of grounded theory, phenomenology end ethnography was chosen, using semistructured interviews for data collection. Three main themes of emotional response, communication and clinical implications were clearly described. Emotional response included feelings of shock and surprise, concern and personal impact. Communication included examples of personal, team and management communication in the days and weeks following the suicide. Clinical aspects discussed included the non-replacement of staff and training and experience as sub-themes. Findings in relation to the wider published literature are discussed

Falls prevention and support:: translating research, integrating services and promoting the contribution of service users for quality and innovative programmes of care

Falls are a significant threat to the safety, health and independence of older citizens. Despite the substantial evidence that is available around effective falls prevention programmes and interventions, their translation into falls reduction programmes and policies has yet to be fully realised. While hip fracture rates are decreasing, the number and incidence of fall-related hospital admissions among older people continue to rise. Given the demographic trends that highlight increasing numbers of older people in the UK, which is broadly reflected internationally, there is a financial and social imperative to minimise the rate of falls and associated injuries. Falling is closely aligned to growing older (Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010). According to the World Health Organization, around 30% of older people aged over 65 and 50% of those over 80 will fall each year (Falls Fact Sheet Number 344, WHO, Geneva, 2010). Falls happen as a result of many reasons and can have harmful consequences, including loss of mobility and independence, confidence and in many cases even death (Cochrane Database Syst Rev 15, 2009, 146; Slips, Trips and Falls Update: From Acute and Community Hospitals and Mental Health Units in England and Wales, Department of Health, HMSO, London, 2010; Falling Standards, Broken Promises: Report of the National
Audit of Falls and Bone Health in Older People 2010, Health Care Quality
Improvement Partnership, London, 2011). What is neither fair nor correct is the
common belief by old and young alike that falls are just another inconvenience to put up with. The available evidence justifiably supports the view that well-organised services, based upon national standards and expert guidance, can prevent future falls among older people and reduce death and disability from fractures. This paper will draw from the UK, as an exemplar for policy and practice, to discuss the strategic direction of falls prevention programmes for older people and the partnerships that need to exist between researchers, service providers and users of services to translate evidence to the clinical setting. Second, it will propose some mechanisms for disseminating evidence to healthcare professionals and other stakeholders, to improve the quality and capacity of the clinical workforce.

Substance misuse in life and death in a 2-year cohort of suicides

Background: Although substance misuse is a key risk factor in suicide, relatively little is known about the relationship between lifetime misuse and misuse at the time of suicide.

Aims: To examine the relationship between substance misuse and subsequent suicide.

Method: Linkage of coroners' reports to primary care records for 403 suicides occurring over 2 years.

Results: With alcohol misuse, 67% of the cohort had previously sought help for alcohol problems and 39% were intoxicated at the time of suicide. Regarding misuse of other substances, 54% of the cohort was tested. Almost one in four (38%) tested positive, defined as an excess of drugs over the prescribed therapeutic dosage and/or detection of illicit substances. Those tested were more likely to be young and have a history of drug misuse.

Conclusions: A deeper understanding of the relationship between substance misuse and suicide could contribute to prevention initiatives. Furthermore, standardised toxicology screening processes would avoid diminishing the importance of psychosocial factors involved in suicide as a 'cause of death'.

The Relationship Between Cumulative Adversity in Childhood and Adolescent Suicide and Accidental Death

On the whole research has concluded that most young people navigate adolescence with few difficulties, but a minority do find this stage of life challenging, and their ways of coping may have negative consequences for both themselves and others. For some the experience of adversity in earlier childhood, and the cumulative impact of multiple adversities has the potential to compromise a young person’s natural resilience. In some cases this may result in an adolescent feeling overwhelmed, and dying through suicide or other high risk behaviours. This article explores these issues with reference to eight young people who died by suicide in Northern Ireland. The article argues that young people exposed to multiple adversities in childhood require earlier, more sustained and better co-ordinated services from professionals if their psychological and emotional well-being is to be promoted.

European Recommendations for Primary Prevention of Congenital Anomalies: A Joined Effort of EUROCAT and EUROPLAN Projects to Facilitate Inclusion of This Topic in the National Rare Disease Plans

Congenital anomalies (CA) are the paradigm example of rare diseases liable to primary prevention actions due to the multifactorial etiology of many of them, involving a number of environmental factors together with genetic predispositions. Yet despite the preventive potential, lack of attention to an integrated preventive strategy has led to the prevalence of CA remaining relatively stable in recent decades. The 2 European projects, EUROCAT and EUROPLAN, have joined efforts to provide the first science-based and comprehensive set of recommendations for the primary prevention of CA in the European Union. The resulting EUROCAT-EUROPLAN 'Recommendations on Policies to Be Considered for the Primary Prevention of Congenital Anomalies in National Plans and Strategies on Rare Diseases' were issued in 2012 and endorsed by EUCERD (European Union Committee of Experts on Rare Diseases) in 2013. The recommendations exploit interdisciplinary expertise encompassing drugs, diet, lifestyles, maternal health status, and the environment. The recommendations include evidence-based actions aimed at reducing risk factors and at increasing protective factors and behaviors at both individual and population level. Moreover, consideration is given to topics specifically related to CA (e.g. folate status, teratogens) as well as of broad public health impact (e.g. obesity, smoking) which call for specific attention to their relevance in the pre- and periconceptional period. The recommendations, reported entirely in this paper, are a comprehensive tool to implement primary prevention into national policies on rare diseases in Europe.