Erik Monasterio

Off-Label Use of Atypical Antipsychotics

Licensed indications for medicines were designed to regulate the claims that can be made about a medicine by a pharmaceutical company. Off-label prescribing (i.e. prescribing a drug for an indication outside of that for which it is licensed) is legal and an integral part of medical practice. In psychiatry, off-label prescribing is common and gives clinicians scope to treat patients who are refractory to standard therapy or where there is no licensed medication for an indication. However, efficacy or safety of such off-label use may not be established.There is a growing list of licensed indications for atypical antipsychotics (AAP) beyond schizophrenia and bipolar affective disorder, and also more evidence for other indications where pharmaceutical companies have not obtained a license. Pharmaceutical companies have promoted AAPs for off-label indications to increase sales and consequently have been fined by the US FDA for this.Since the 1990s, AAP use has expanded considerably, for example, the off-label use of quetiapine alone accounted for an estimated 17% of the AAP spend in New Zealand in 2010. There are a number of potential problems with the expanded use of AAPs outside of schizophrenia and related psychoses. A larger population will be exposed to their adverse effects, which include weight gain, type 2 diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. There are also concerns with the abuse of these agents, in particular quetiapine.Given that an increasing percentage of the population is being treated with these agents, off-label prescribing of AAPs is a cause for concern; they have a propensity to cause significant side effects and their efficacy and long-term safety for most off-label indications remains largely unknown, and therefore the risks and benefits of their use should be carefully weighed up prior to prescribing these agents off-label.

Personality characteristics in a population of mountain climbers

OBJECTIVE Mountaineering and mountain-related sports are growing in popularity and are associated with significant risk of injury. There is a perception that mountaineers possess unique personality characteristics that attract them to the sport. We aim to determine whether there are any identifiable differences between the personality characteristics of experienced mountaineers and a normal control population and to determine whether there is an association between specific personality traits and risk of injury. METHODS Questionnaires were utilized to obtain data on demographics, accidents, and personality characteristics from a population of experienced mountaineers. The Temperament and Character Inventory (TCI) was used, and the results were compared with normative data from age-matched controls. RESULTS Forty-seven mountaineers from 8 different countries enrolled in the study. The mean age was 33 years, and 44 (90%) had been mountaineering for more than 5 years. Twenty-three climbers (49%) had been involved in a total of 33 accidents. Mountaineers scored higher on novelty seeking (P < .05) and self-directedness (P < .05) and lower on harm avoidance (P < .001) and self-transcendence (P < .001). There was a significant association between the character measure of cooperativeness and the total number (-.33, P < .05) and severity (-.475, P < .05) of accidents. CONCLUSIONS Mountaineering is associated with significant risk of injury. Wide variation in the scores of personality traits suggests that there is not a tightly defined personality profile among mountaineers. Scores on cooperativeness may assist in determining risk of injury in mountaineers.

Personality characteristics of BASE jumpers.

BASE jumping is an extreme sport, which is associated with significant risk of injury and death. We aimed to determine whether BASE jumpers have different personality characteristics to an age-matched, normal control population. An international population of BASE jumpers was examined using the Temperament and Character Inventory (TCI). Mean age was thirty-four years; fifty-nine (87%) jumpers were male; twenty-eight (41%) jumpers had sustained a significant injury. A substantial proportion of the BASE jumpers presented extremely low scores in the temperament measure of Harm Avoidance (p < 0.001); the extent of which has not been reported in any other population.

The epidemiology of severe and catastrophic injuries in BASE jumping.

Objective:To report the demographic characteristics, injury rate, severity, and morbidity in BASE jumping. Design:Cross-sectional survey. Setting:BASE jumping group meetings from 2006 to 2010. Participants:Heterogenic group of 102 International BASE jumpers. Assessment of Risk Factors:Injuries reported as function of jumps made, jumping days, age, experience, and sex. Main Outcome Measures:Incidence, severity, and type of injuries. Results:Responses from 68 subjects were available for analysis. The median number of jumps was estimated at 286 per respondent. The median time respondents had participated in BASE jumping was 5.8 years. There were 39 reported severe injuries sustained by 29 different jumpers. Nineteen thousand four hundred ninety-seven jumps were reported, resulting in 2 severe injuries per 1000 jumps (0.2% severe injury rate) or 2.6 severe injuries per 1000 jumping days. Forty-nine respondents (72%) had witnessed the death or serious injury of other participants in the sport. Twenty-four accidents (61%) involved the lower limbs, 8 (20%) the back/spine, 7 (18%) the chest wall, and 5 (13%) were a head injury. The mean Abbreviated Injury Score was 3.2 (range, 2-5). Fifteen (52%) of the 29 injured jumpers required 20 acute surgical interventions, which were mostly orthopedic related. There was a significant correlation between number of jumps made and injuries sustained (P < 0.05). Conclusions:BASE jumpers have an average of 1 severe injury for every 500 jumps. Most active BASE jumpers have witnessed death or severe injury of a participant and have experienced a “close call” incident.

Fatalities in wingsuit BASE jumping.

OBJECTIVE To analyze fatality data associated with wingsuit use in an international case series of fixed-object sport parachuting (BASE jumping) to identify incident and injury mechanisms and to form a basis for potential prevention measures and future safety recommendations. METHODS A descriptive epidemiological study was performed of fatal injury events occurring in wingsuit BASE jumping. Fatalities (n = 180) were sequentially analyzed assessing human, equipment, and environmental factors from 1981 to 2011. Main outcome measures included descriptions of typical fatal incident and injury mechanisms. RESULTS Of the 180 fatal events, 39 (22%) were related to use of wingsuits; 38 (97%) launched from cliffs and 1 (3%) from a building. Of the 39 fatalities, 19 (49%) were caused from cliff strikes, 18 (46%) from ground impact, and 1 (3%) from a building strike. Thirty-eight (97%) of the fatalities were male. During 2002 to 2007 there was a total of 61 BASE jumping deaths, 10 (16%) of which were related to the use of wingsuits, whereas during 2008 to 2011 there was a total 59 fatal events, of which 29 (49%) were related to the use of wingsuits. Seventeen fatalities (39%) were attributed to wingsuit path miscalculation. In the first 8 months of 2013, 17 of 19 (90%) fatalities were wingsuit related. Most fatalities occurred between April and October, reflecting a seasonal increase in activity in the northern hemisphere summer. CONCLUSIONS Wingsuit-related BASE jump fatalities appear to be increasing as wingsuit BASE jumping increases in popularity. Most fatalities are attributed to cliff or ground impact, and are mostly the result of flying path miscalculation.

The Trans Pacific Partnership Agreement: Exacerbation of inequality for patients with serious mental illness

Negotiations for a treaty that is set to become one of the world’s biggest trade agreements, the Trans Pacific Partnership Agreement (TPPA), have sparked considerable concern and debate about the possible impacts on health. The TPPA negotiations involve a diverse set of 12 countries from around the Pacific Rim. These include developed countries such as Australia, New Zealand, the United States and Canada, along with much lower-income countries such as Vietnam and Peru.While few details about the nego-tiations are publicly available, the TPPA is said to comprise approxi-mately 29 chapters, which include legal rules covering issues such as investor protections, intellectual property rules and regulatory coher-ence along with more traditional trade issues such as the removal of tariffs. A number of recent reviews based on leaked negotiating docu-ments conclude that there are legiti-mate concerns about the potential impact of the TPPA in relation to ensuring equitable access to medi-cines and public health regulation, including tobacco, food and alcohol regulation (see, for example, Hirono et al., 2014; Wyber and Perry, 2013).While many of the health-related impacts of the TPPA can be expected to be population-wide, many of the impacts will be differentially distrib-uted. People in low-income countries and disadvantaged groups within par-ticipant countries, including those of low socioeconomic status, Indigenous people and those with chronic ill-nesses and disabilities, are likely to be disproportionately affected (Gleeson et al., 2013; Hirono et al., 2014).The purpose of this article is to consider the likely implications of the TPPA on access to health care and public health initiatives (proposed and actual) to improve the health and lifes-pan of patients suffering from serious mental illness (SMI). SMI includes schizophrenia and related disorders, bipolar disorder, depressive disorder, neurotic disorder and substance use disorder. One of the most consist-ently replicated findings in the social sciences has been the negative rela-tionship of socioeconomic status and SMI, indicating that people with SMI face higher levels of disadvantage com-pared to most other groups in the community (Muntaner et al., 2004).

Indications of atypical antipsychotics in the elderly

Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson’s Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

Quetiapine use: science or clever marketing?

Australian & New Zealand Journal of Psychiatry, 47(1) peripheral field constriction. Further enquiry revealed that there was also a family history of RP in her mother. Her psychiatric symptoms responded to an antipsychotic trial with ziprasidone and she achieved clinical remission. Patient G, a 32-year-old engineering graduate presented with 3 years of continuous illness, characterized by irritability, suspiciousness, and abusive and assaultive behaviour, along with poor personal care. Mental status examination revealed delusions of persecution, reference, and misinterpretation. Her father suffered from RP. Premorbidly, she was well adjusted and was documented to be excelling in academic performance. She was treated with risperidone at a dose of 6 mg/day. During 2 years of follow-up, she was found to be asymptomatic. The first case demonstrates the association and comorbidity of these two disorders, suggesting that there could be shared aetiopathogenic mechanisms for both conditions. In both cases, there is familial sharing of these two disorders among firstdegree relatives, raising the possibility of shared genetic causation. RP refers to a group of hereditary retinal disorders where photoreceptor cells degenerate resulting in progressive deterioration in visual function. Although there are no consistently replicated linkage findings in schizophrenia, there is some evidence for genes at certain chromosomal regions, especially at 6p24-p22 and 8p22-2 (Gottesman and Moldin, 1997), to be associated with the condition. It is interesting to note that schizophrenia along with many other metabolic disturbances and RP have been found to have coding regions in chromosome 6 encoding the major histocompatibility complex, which is important for immune regulation (Avis et al., 1997). Moreover, schizophrenia and the retinoid cascade have been linked to similar gene loci (Goodman, 1998). Retinoic acid regulates genes that are involved in the regulation of dopamine and dopamine receptors (Citver et al., 2002). The demonstration of the association of these disorders and their familial aggregation clinically suggests that common pathogenic mechanism could be operating. Unraveling this mechanism could pave way to the development of newer methods for the treatment of schizophrenia. Funding

Call for transparency in new generation trade deals

604 www.thelancet.com Vol 385 February 14, 2015 One such agreement, the TransPacifi c Partnership agreement (TPPA), is in the fi nal stages of negotiation between 12 Pacific-Rim countries, affecting more than 700 million people. Although USA-based industry advisers have been granted privileged access to negotiating documents, health agencies have been forced to rely on leaks for information. As for the proposed Trans-Atlantic Trade and Investment Partnership between the European Union and the USA, serious concerns about the health eff ects of the TPPA have been highlighted in medical journals and by civil society. The concerns include unprecedented expansion of intellectual property rights that would prolong monopolies on pharmaceuticals and reduce access to affordable and lifesaving generic medicines. Effective price regulation of medicines could also be undermined. Rising medicine costs would disproportionately affect already vulnerable populations, obstructing efforts to improve health equity within and between countries. Investor state dispute settlement (ISDS) provisions allow investors to sue governments if policy changes or even court rulings substantially aff ect the value of their investment, yet do not allow governments to sue investors for breaching the right to health. ISDS processes constrain governments’ abilities to regulate on the basis of the precautionary principle, or even to implement health policies on the basis of established evidence. These processes can have a chilling eff ect on eff orts to address key health issues, such as alcohol, the obesity epidemic, and climate change. In New Zealand, the fear of costly ISDS litigation is already constraining government regulation on tobacco plain packaging. As health practitioners in seven of the involved Pacific-Rim countries, we call on our governments to publicly release the full draft TPPA Hepatinov, Le Kremlin Bicêtre, France (A-MT); INSERM UMR897, Bordeaux, France (XA, DM); UMR-D190, Aix-Marseille Université, IRD, Marseille, France (XdL); Ministry of Health, Conakry, Guinea (SK); and Hôpital Necker – Enfants malades, APHP and EA7327, Université Paris Descartes, Sorbonne Paris Cité, Paris, France (PF)

Rock climbing-related subclavian vein thrombosis.

Paget-Schroetter syndrome, also known as upper extremity deep venous thrombosis (UEDVT), is a rare condition, characterised by a (sub-) total occlusion of the axillary-subclavian venous system due to thrombosis. UEDVT is the most common vascular condition among athletes so far; although the general incidence is low, this problem will become more frequent as a result of increased participation in climbing sports. The purpose of this report is to illustrate two cases in rock climbers where UEDVT developed during rock climbing or bouldering. Fortunately, both patients were diagnosed relatively early after the symptoms began, despite the ambiguity of UEDVT symptoms. This relatively unfamiliar condition may become more highly recognised as a potentially serious differential diagnosis of unspecific pain of the shoulder. Rock climbers are disposed to develop UEDVT due to frequent stress on the upper extremities during training or competition.