Randomised controlled trials and 'unexpected' adverse events associated with newly released drugs : improvements in pharmacovigilance systems are necessary for real-time identification of patient safety risks

Adverse drug events are one of the major causes of morbidity in developed countries, yet the drugs involved in these events have been trialled and approved on the basis of randomised controlled trials (RCTs), regarded as the study design that will produce the best evidence.

Though the focus on adverse drug events has been primarily on processes and outcomes associated with the use of these approved drugs, attention needs to be directed to the way in which the RCT study design is structured. The implementation of controls to achieve internal validity in RCTs may be the very controls that reduce external validity, and contribute to the levels of adverse drug events associated with the release of a new drug to the wider patient population.

An examination of these controls, and the effects they can have on patient safety, underscore the importance of knowing about how the clinical trials of a drug are undertaken, rather than relying only on the recorded outcomes.

As the majority of new drugs are likely to be prescribed to older patients who have one or more comorbidities in addition to that targeted by a new drug, and as the RCTs of those drugs typically under-represent the elderly and exclude patients with multiple comorbidities, timely assessment of drug safety signals is essential.

It is unlikely that regulatory jurisdictions will undertake a reassessment of safety issues for drugs that are already approved. Instead, reliance has been placed on adverse drug event reporting systems. Such systems have a very low reporting rate, and most adverse drug events remain unreported, to the eventual cost to patients and healthcare systems.

This makes it essential for near real-time systems that can pick up safety signals as they occur, so that modifications to the product information (or removal of the drug) can be implemented.

How does perceived risk mediate associations between perceived safety and parental restriction of adolescents' physical activity in their neighborhood?

Background
There is evidence that adolescence is a critical period of decline in physical activity. However, adolescents may have limited opportunities to be physically active outdoors if their parents are concerned about neighborhood safety and restrict their adolescent’s physical activity within their neighborhood. Pathways that lead to parental restriction of adolescents’ physical activity (constrained behavior) are under-researched. This study aimed to examine perceived risk as a potential mediator of associations between perceived safety/victimization and constrained behavior.
Methods
Cross-sectional study of adolescents (43% boys) aged 15–17 years (n = 270) in Melbourne, Australia. Parents reported perceived safety (road safety, incivilities and personal safety) and prior victimization in their neighborhood, perceived risk of their children being harmed and whether they constrained their adolescent’s physical activity. Constrained behavior was categorized as ‘avoidance’ or ‘defensive’ behavior depending on a whether physical activity was avoided or modified, respectively, due to perceived risk. MacKinnon’s product-of-coefficients test of mediation was used to assess potential mediating pathways between perceived safety/victimization and constrained behavior.
Results
For girls only, perceived risk was a significant mediator of associations between perceived road safety and avoidance/defensive behavior, and between perceived incivilities, perceived personal safety, victimization and defensive behavior.
Conclusions
Associations between perceived safety/victimization and constrained behavior are complex. Findings may guide the design of interventions that aim to improve actual and perceived levels of safety and reduce perceptions of risk. This is of particular importance for adolescent girls among whom low and declining levels of physical activity have been observed worldwide.

Do parents’ and children’s concerns about sports safety and injury risk relate to how much physical activity children do?

Objective To see whether concerns about injury risk relate to children's physical activity (PA).
Methods Two cohorts were recruited from 19 Australian schools and assessed in 2001 (T1), 2004 (T2) and 2006 (T3). The younger (n=162) was assessed at 6, 9 and 11years old, and the older (n=259) at 11, 14 and 16 years old. At T1 and T2, parents of the younger cohort reported on fear of child being injured, and whether child would be at risk of injury if they played organised sport; the older cohort self-reported injury fear. Accelerometers assessed PA at each time point. Linear regression models examined cross-sectional associations, and also associations between T1 injury fear and risk and T2 PA, and T2 injury fear and risk and T3 PA.
Results In the younger cohort at T2 (9 years), fear and risk were both negatively associated with moderate to vigorous PA (MVPA) (β=−0.17, 95% CI −0.30 to −0.03 and β=−0.26, 95% CI −0.41 to −0.10) and also vigorous PA (VPA). Fear was also associated with moderate PA (MPA). For the older cohort at T1, injury fear was negatively associated with MVPA (β=−0.21, 95% CI −0.35 to −0.07) and also MPA and VPA. Parental perception of risk at T1 (6 years) was negatively associated with children's MPA at T2 (9 years) (β=−0.17, 95% CI −0.32 to −0.02). Sex did not moderate any association.
Conclusions Younger children and their parents need to know which sports have low injury risks. Some children may need increased confidence to participate.

Balanced efficacy, safety, and tolerability recommendations for the clinical management of bipolar disorder

Objective:  To provide practical and clinically meaningful treatment recommendations that amalgamate clinical experience and research findings for each phase of bipolar disorder.

Methods:  A comprehensive search of the literature was undertaken using electronic database search engines (Medline, PubMed, Cochrane reviews) using key words (e.g., bipolar depression, mania, treatment). All relevant randomised controlled trials were examined, along with review papers, meta-analyses, and book chapters known to the authors. In addition, the recommendations from accompanying papers in this supplement have been distilled and captured in the form of summary boxes. The findings, in conjunction with the clinical experience of international researchers and clinicians who are practiced in treating mood disorders, formed the basis of the treatment recommendations within this paper.

Results:  Balancing clinical experience with evidence informed and lead to the development of practical clinical recommendations that emphasise the importance of safety and tolerability alongside efficacy in the clinical management of bipolar disorder.

Conclusions:  The current paper summarises the treatment recommendations relating to each phase of bipolar disorder while providing additional, evidence-based, practical insights. Medication-related side effects and monitoring strategies highlight the importance of safety and tolerability considerations, which, along with efficacy information, should be given equal merit.

'Without fists' : age-mixing and its influence on safety and criminal contamination in women's prisons

Prisons are often considered to be places where violence and intimidation prevail, and where young prisoners are at risk of victimisation from adult prisoners. For this reason, youth in custody are housed separately from adult offenders in most Western jurisdictions. In New Zealand, for a variety of reasons, a separate facility for young women in custody is not provided as it is for young men. Therefore, researchers were able to conduct a study to investigate the experience of age-mixing from the point of view of young women in custody. Dominant notions of what constitutes contamination and who perpetrates violence in the custodial setting have been challenged as a result of analysis of this data. In fact, young women who were age-mixed in custody asserted that age-mixing has the effect of decreasing the degree and impact of the prevailing violent culture.

Is there a need for safety monitoring guidelines for antidepressant treatment?

Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. The World Health Organisation estimates that depression effects approximately 121 million people worldwide, with 26 million people receiving some form of medical care for depression [1]. A large number of these people will be treated with antidepressants. Moreover, antidepressants are commonly administered to special populations, such as the elderly, children and women during reproductive life stages. Depression is also commonly associated with comorbid physical illnesses [2], being overweight [3], tobacco smoking [4], poor diet [5] and lack of physical activity [6]. Large numbers of people being treated, often with vulnerabilities, increases the likelihood of adverse drug reactions to antidepressant treatment.

You say security, we say safety : speaking and talking ‘security’ in Kyrgyzstan

The Copenhagen School's notion of securitization is widely recognised as an important theoretical innovation in the conceptualisation of security, not least for its potential for including a range of actors and spatial scales beyond the state. However, its empirical utility remains more open to question due to a lack of reflexivity regarding local socio-cultural contexts, narrow focus on speech and inherently retrospective nature. Drawing on fieldwork conducted by the author in Kyrgyzstan between September 2005 and June 2006, this paper will examine the implications of these limitations for conducting empirical research on "security" logistically and methodologically. Centrally, the question of how “security” can be researched in the field will be discussed. Consideration will be given to the researcher’s role in talking “security” and how “security” can effectively be located and explicated through the creation of ethnomethodological “thick description”. Issues of contingency, multiple voices and power loci, and inter-cultural translation will be addressed. The paper will conclude with a consideration of how local knowledge can be used to inform our research and help find ways to bridge the divide between the field and theory.

Occupational health and safety among commercial sex workers

The concept of occupational health and safety (OHS) for commercial sex workers has rarely been investigated, perhaps because of the often informal nature of the workplace, the associated stigma, and the frequently illegal nature of the activity. We reviewed the literature on health, occupational risks, and safety among commercial sex workers. Cultural and local variations and commonalities were identified. Dimensions of OHS that emerged included legal and policing risks, risks associated with particular business settings such as streets and brothels, violence from clients, mental health risks and protective factors, alcohol and drug use, repetitive strain injuries, sexually transmissible infections, risks associated with particular classes of clients, issues associated with male and transgender commercial sex workers, and issues of risk reduction that in many cases are associated with lack of agency or control, stigma, and legal barriers. We further discuss the impact and potential of OHS interventions for commercial sex workers. The OHS of commercial sex workers covers a range of domains, some potentially modifiable by OHS programs and workplace safety interventions targeted at this population. We argue that commercial sex work should be considered as an occupation overdue for interventions to reduce workplace risks and enhance worker safety.

Ensuring implementation success : how should coach injury prevention education be improved if we want coaches to deliver safety programmes during training sessions?

Coaches play a major role in encouraging and ensuring that participants of their teams adopt appropriate safety practices. However, the extent to which the coaches undertake this role will depend upon their attitudes about injury prevention, their perceptions of what the other coaches usually do and their own beliefs about how much control they have in delivering such programmes. Fifty-one junior netball coaches were surveyed about incorporating the teaching of correct (safe) landing technique during their delivery of training sessions to junior players. Overall, >94% of coaches had strongly positive attitudes towards teaching correct landing technique and >80% had strongly positive perceptions of their own control over delivering such programmes. Coaches’ ratings of social norms relating to what others think about teaching safe landing were more positive (>94%) than those relating to what others actually do (63–74%). In conclusion, the junior coaches were generally receptive towards delivering safe landing training programmes in the training sessions they led. Future coach education could include role modelling by prominent coaches so that more community-level coaches are aware that this is a behaviour that many coaches can, and do, engage in.

A safety culture in construction business

Promoting safety management is always the top priority in construction business. Fostering safety culture will be one of the most effective ways. This paper is a case study, based upon the “Geller’s 10 principles for achieving a total safety culture”, to review how a construction companyin Hong Kong effectively promoting safety culture and enjoying pleasant safety records. Zero harmis not a “zero sum game”, but it requires positive “top down” and “bottom up” actions from both employers and employees.