Bariatric Surgery for Severely Obese Adolescents

Bariatric Surgery for Severely Obese Adolescents

Paediatric Respiratory Reviews 15 (2014) 227–230 Contents lists available at ScienceDirect Paediatric Respiratory Reviews Mini-Symposium: Obesity a...

275KB Sizes 0 Downloads 176 Views

Paediatric Respiratory Reviews 15 (2014) 227–230

Contents lists available at ScienceDirect

Paediatric Respiratory Reviews

Mini-Symposium: Obesity and the Respiratory system

Bariatric Surgery for Severely Obese Adolescents Dominic A. Fitzgerald 1,2,*, Louise Baur 2,3 1

Department of Respiratory Medicine, The Children’s Hospital at Westmead, Sydney, NSW, Australia Sydney Medical School, Discipline of Paediatrics & Child Health, University of Sydney, Sydney, NSW, Australia 3 Weight Management Services, The Children’s Hospital at Westmead, Sydney, NSW, Australia 2

EDUCATIONAL AIMS The reader will come to appreciate:  The numbers of severely obese teenagers are increasing and many of these people will suffer multiple lifestyle impacting co-morbidities including Type 2 diabetes mellitus, hypertension, obstructive sleep apnoea and arthritis.  Severe obesity in the teenage years is associated with premature cardiovascular disease unless significant weight reduction occurs.  Bariatric surgery is suited to mature, severely obese adolescents who have been unable to achieve significant weight reduction with medical and lifestyle interventions.  Bariatric surgery should be provided in the setting of a multi-disciplinary weight management service with ongoing follow-up into the adult years.

A R T I C L E I N F O

S U M M A R Y

Keywords: Bariatric surgery Severe obesity Adolescents Weight management Co-morbidities Premature death Follow-up

Severe obesity is increasing in adolescents and is associated with cardiovascular disease, type 2 diabetes mellitus, obstructive sleep apnoea, polycystic ovarian syndrome and a range of musculoskeletal problems. Premature death is the inevitable outcome of persistent severe obesity in adolescents. In adults with severe obesity, medical and lifestyle interventions have been shown to be expensive and less effective in terms of weight loss than has bariatric surgery. The single completed randomised controlled trial in adolescents shows the same outcome. This is supported by meta analyses of bariatric surgery in adolescent subjects. A more aggressive approach to severe obesity, utilising bariatric surgery in selected cases, within the context of a multi-disciplinary team, is required. ß 2014 Published by Elsevier Ltd.

The scale of the problem of obesity in society has outflanked medical service provision. Despite clear evidence of the changing physical demographics in developed and developing populations, governments and health systems have been unable to respond effectively to the problems associated with severe obesity. The health care cost of obesity was estimated in the United States alone to be $US147 billion in 2009 [1] or between 5% and 10% of the US health care budget by another estimation. [2]. The astounding costs merely reflect that obesity is entrenched in our societies and forebodes ominously of increased costs unless systematic measures are undertaken.

* Corresponding author. Department of Respiratory Medicine, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia 2145 Tel.: +61 2 9845 3397; fax: +61 2 9845 3396. E-mail address: Dominic.fi[email protected] (D.A. Fitzgerald). http://dx.doi.org/10.1016/j.prrv.2014.06.001 1526-0542/ß 2014 Published by Elsevier Ltd.

INCREASING OBESITY IS A GLOBAL PHENOMENON Comparisons have shown that in the United States, United Kingdom and Australia, the prevalence of obesity in adults has doubled in the last 25 years, whilst the prevalence in Europe ranges between 40% and 60% [3]. In children, the proportion of obese children is increasing and the greatest increase is in those with the highest body mass index [BMI]. In the United Kingdom, the proportion of 11-15 years old with obesity was 14.7% in 1995 and this increased to 18.3% in 2010 [4]. In the United States, the National Health and Nutrition Examination Survey data from 2009-2010 revealed that 31.8% of children aged 2 to 19 years were overweight [BMI  85%] and 16.9% were obese [BMI  95%] [5]. Other data have shown that 84% of obese children will become obese adults [6] and 37% of obese male adolescents and 51% of obese female adolescents will become severely obese by their 30s

228

D.A. Fitzgerald, L. Baur / Paediatric Respiratory Reviews 15 (2014) 227–230

[7].Consequently, obesity represents one of the greatest health concerns in the developed world, but its prevalence is also increasing in the developing world. Given the world’s population distribution, obesity and severe obesity and their consequences appear to be one of the major threats to global healthcare in an era with improved infectious disease prevention through vaccination and treatment [eg HIV and TB] as well as improving childbirth mortality figures. CONSEQUENCES OF OBESITY The short to medium term consequences of obesity in children and adolescents are well established. These include insulin resistance and type 2 diabetes mellitus, hypertension, acanthosis nigricans, obstructive sleep apnoea, fatty liver disease, polycystic ovary syndrome and degenerative joint disease [8–10]. The longer term outlook is similarly guarded, with increased risks of premature death from cardiovascular events and malignancies, including bowel cancer [8,11]. The increased risk of premature death has been estimated to decrease the life expectancy of an obese adolescent by between 5 and 20 years, depending on race and gender [12]. The added burden of psychological stresses including bullying, isolation and discrimination, are pervasive [8]. OVERVIEW OF TREATMENT OF OBESITY Systematic reviews of paediatric obesity show that behavioural lifestyle interventions can lead to positive, albeit relatively moderate, outcomes in weight, BMI, other measures of body fatness and cardio-metabolic risk factors [13,14]. While no one treatment programme can be recommended, the key elements of obesity treatment are well-established [13,14]: treatment of comorbidities; family engagement; a developmentally appropriate approach; long-term behaviour change; dietary change; increased physical activity; decreased sedentary behaviours; improved sleep pattern and duration; long-term weight maintenance strategies; and consideration of the use of pharmacotherapy and other forms of nonconventional therapy. However, there can be major challenges in service provision, including inadequate clinic staffing, the need to treat patients with a range of medical and psychological co-morbidities, and the impact of social disadvantage on engagement in treatment plans. A further concern is that, for severely obese patients, particularly adolescents, medical management alone may be inadequate. In this situation, the option of bariatric surgery warrants consideration. The magnitude of the problem has led to the establishment of weight management services in some large paediatric teaching hospitals in the developed world. Through these multi-disciplinary services a number of strategies are employed aimed at increasing physical activity, reducing caloric intake and the consideration of pharmacotherapies [3]. The success of such resource intense programmes may be slow and modest in terms of weight loss achieved, psychological benefits and impact upon the progression of underlying co-morbidities when compared to bariatric surgery. The reasons for the relative lack of traction with severely obese adolescents in weight management services are likely multifactorial, involving lack of motivation, psycho-social problems within the family unit, socio-economic deprivation and mood issues [3]. The focus of care in severely obese adolescents [BMI > 40 kg/ m2], and especially those with co-morbidities, who have failed to achieve significant improvements with an appropriate trial of medical therapy is consideration of surgery. Such an escalation of treatment must consider the cognitive competence of the adolescent, their physical maturity, their adherence with therapy

to date and their continued engagement with the multi-disciplinary weight management services into their adult years [15]. This has prompted paediatric clinicians to follow their adult medicine colleagues in broadening treatment options in severely obese patients to consider bariatric surgery. There is no universal agreement upon the minimum age or the degree of obesity threshold for consideration of bariatric surgery in adolescents. However, there are appropriate concerns regarding understanding of the procedure and its longer term consequences, cognition, intellectual competence and the ability to meet standards for informed consent. This has resulted in specialist groups combining to provide recommendations for bariatric surgery in severely obese adolescents. One recent joint recommendation from the Australian and New Zealand Association of Paediatric Surgeons, the Obesity Surgery Society of Australia and New Zealand, and the Paediatrics & Child Health Division of The Royal Australasian College of Physicians was published in 2010 [16]. This working party suggested that the threshold for bariatric surgical intervention would be a body mass index (BMI) >40 kg/m2. However, the recommendation was extended to include adolescents with a BMI >35 kg/m2 in the presence of severe obesityassociated complications such as type 2 diabetes, hypertension, non-alcoholic steatohepatitis, benign intracranial hypertension or obstructive sleep apnoea. Additional considerations about intellectual competence are summarised in Table 1 and contra-indications for bariatric surgery from the same consensus statement are listed in Table 2 [16]. TYPES OF BARIATRIC SURGERY There are four types of bariatric surgery which are usually performed laparoscopically. These include gastric bypass surgery with a Roux-en-Y procedure [RYGB], adjustable gastric banding [AGB], sleeve gastrectomy [SG] and bilio-pancreatic diversion [BPD]. In obese adolescents, both the RYGB and AGB have been the techniques most commonly used [17]. The RYGB involves the creation of a 30 ml pouch of upper stomach that is anastomosed to the dissected jejunum which results in food bypassing the rest of the stomach and proximal small bowel which is re-connected to the jejunum, thereby creating a ‘‘Y’ shape [18]. This allows biliopancreatic secretions to mix with food and facilitate absorption [17]. The AGB procedure is simpler and therefore easier to undertake [17,19]. It involves the positioning of a band around the proximal stomach, approximately 1-2 cm from the gastro-oesophageal junction to form a gastric pouch of approximately 30 ml volume [19]. The sleeve gastrectomy operation involves the resection of the greater curvature of the stomach which leaves a tubular stomach of less than 15% of its original volume [20]. The final operation is the biliopancreatic diversion which incorporates components of both the SG and RYGB [17]. The exact mechanisms

Table 1 Patient criteria for selection for bariatric surgery in adolescents with severe obesity.  Age 15 years, although surgery may be considered in exceptional circumstances at age 14 years  Tanner stage 4 or 5 pubertal development  Attainment of final or near-final adult height (i.e. bone age 13.5 in females and 15.5 in males)  Persistence of the level of obesity despite involvement in a formal multidisciplinary and supervised program of lifestyle modification and pharmacotherapy. A minimum of 6 months of supervised multidisciplinary therapy should be provided prior to bariatric surgery being performed  The adolescent and family understand, and are motivated to participate in the on-going treatment, lifestyle change and review following surgery  The adolescent is able to provide informed consent for the surgery

D.A. Fitzgerald, L. Baur / Paediatric Respiratory Reviews 15 (2014) 227–230 Table 2 Bariatric surgery is not recommended for the following adolescents. Adolescents under the age of 14 years Pregnant or breast-feeding adolescents Patients with significant cognitive disabilities Patients with an untreated or untreatable psychiatric or psychological disorder  Patients with Prader-Willi syndrome and other similar hyperphagic conditions.

   

of action to achieve weight loss are unclear but appear to go beyond caloric intake restriction and will involve changed gut physiology with altered gut hormone and brain interaction [17]. EXPERIENCE WITH BARIATRIC SURGERY IN ADULTS Evidence clearly supports the ability of bariatric surgery to achieve significantly greater weight gain than integrated multidisciplinary medical, dietary and lifestyle management strategies. The 2009 Cochrane review on surgery for obesity in adults showed the efficacy of bariatric surgery but commented on the complications that may occur and the lack of relatively long term data in follow up [21]. The short term benefits for quality of life measures show consistent short term benefits [21]. As noted by Black et al. [17], the meta-analysis of Buchwald et al [22] estimated that gastric banding in adults achieved a fall in BMI of between -10.4 and -16.7 kg/m2. Similarly, this paper reported that dyslipidaemia resolved in 70%, type 2 diabetes mellitus in 77%, hypertension in 62% and obstructive sleep apnoea in 86% after bariatric surgery [22]. There are risks with bariatric surgery which are well documented. Complication rates may to a degree relate to the experience of the surgeon and the surgical unit undertaking the procedures. Even allowing for the fact that most bariatric surgery is performed laparoscopically, there is a small but significant mortality risk in adults who undergo surgery [21]. This relates to the inherent anaesthetic risk for obese people related to their well-established co-morbidities. The risks are greater with the more severely obese patients who undergo the more invasive operations such as RYGB and SG, as opposed to the less invasive GB [21]. However, the re-operation rate for GB is higher, albeit often for repositioning of bands that have slipped. As would be expected, the more radical the surgery, as with RYGB and SG, the greater the long term issues such as metabolic effects including micronutrient deficiencies [17,23]. There are also concerns about the lack of long term follow-up data in adult populations. EXPERIENCE WITH BARIATRIC SURGERY IN ADOLESCENTS The numbers of adolescent patients undergoing bariatric surgery are rising but accurate figures are scarce [24]. Data from the USA show that 2744 cases of bariatric surgery were undertaken in obese adolescents between 1996 and 2003[24]. The experience is limited to a relatively small number of centres, with ongoing concerns relating to the criteria applied for who should receive the surgery [17]. Most cases are likely decided upon by multidisciplinary teams in a local setting, although some national guidelines have recently emerged [16]. Most experience from case series and meta-analyses has suggested that weight loss is achieved with surgery in the early years with reduction in comorbidities persisting over time. However, the long term data are surprisingly limited in detail when one considers the thousands of adults who have undertaken bariatric surgery of various types over the last two decades [17,25–27]. A single randomised controlled trial of laparoscopic adjustable bariatric surgery (AGB) compared with an optimal multicomponent

229

lifestyle programme was reported by Olbers et al. in 2010 [28]. Patients were recruited from a paediatric weight management clinic service and were aged between 14 and 18 years at enrolment. To enter, they needed to be intellectually competent, have a BMI > 35 kg/m2 and have identifiable medical complications which could include metabolic syndrome, a physical limitation or a psycho-social problem. The medical group of 25 patients received individual calorie reduction diet plans, activity targets mediated by pedometers, a formalised exercise regimen and six weekly health care practitioner review. The surgical group also contained 25 patients. There were 8 dropouts [16%], one in the surgical intervention group and seven in the control group, meaning 96% finished the two year study in the intervention group and 72% in the control group. The mean age at entry was 16.5 years in the AGB group and 16.6 years in the control group. Females predominated in both groups: 64% in the AGB group and 72% in the control group. The mean BMI at entry was 42.3 [SD: 6.1] kg/m2 in the AGB group and 40.4 [SD 3.1] kg/m2 in the control group. Metabolic syndrome was present in 36% [AGB] and 40% [controls]. Consistent with adult data [3,21], both groups lost weight but the weight loss was significantly greater [approximately ten fold] in the AGB group than the control group: Weight loss 34.6 kg [95% CI: 30.2, 39.0] vs 3.0 kg [2.1, 8.1] and BMI: -12.7 [95% CI 11.3, 14.2] kg/m2 vs -1.3 [0.4, 2.9] kg/m2. The proportion of patients with the metabolic syndrome fell from 36% to zero in the AGB group and from 40% to 22% in the control group. Surgical complications were consistent with the adult literature. Subjectively measured quality of life improvements were apparent for both groups. For the surgical group there were improvements in physical functioning, general health and self-esteem and for the control group there were more modest gains as reflected in general health. No other randomised controlled trials in his age group have been undertaken. The most recent meta-analysis on bariatric surgery in children and adolescents was performed by Black and colleagues [17]. This included one randomised controlled trial and 22 uncontrolled before and after studies which met the inclusion criteria [main criterion was change in BMI at 12 months and data on comorbidities]. The median number of patients in each study was 24, females predominated [51% to 81% in series], and the mean baseline BMI at entry was 47.9 kg/m2. The average weighted mean BMI difference from baseline to 1 year was -13.5 kg/m2 [95% CI 15.1, -11.9]. The surgery types and populations differed, giving strong evidence of heterogeneity among the studies [17]. Weight loss differed by operation type. The greatest fall in BMI was seen in patients undergoing RYGB [-17.2 kg/m2, CI -20.1, -14.3] in 8 studies [n=256 patients] and smallest for those undergoing AGB [-10.5 kg/ m2, CI -11.8, -9.1] in 11 studies [n=271 patients]. In the meta-analysis of Black and colleagues [17], the perioperative outcomes were expressed in different ways and were difficult to compare between surgery types. In RYGB studies, the main problems reported included nutrient deficiencies, hernias, wound infections and small bowel obstructions, cholelithiasis and ulcers. In contrast, the complications reported with AGB were less frequent and included pouch dilation, port leakage, band slippage requiring remedial operations. Conversions to other surgery or reversal of the procedure were more common with AGB than RYGB. The reporting of co-morbidities out to one year was inconsistent. There was evidence to suggest that co-morbidity resolution occurred for hypertension, obstructive sleep apnoea, type 2 diabetes mellitus and dyslipidemia and this was more evident with RYGB. A number of studies used validated quality of life tools to demonstrate consistent improvements in physical and psychological outcomes. The results were similar to the only previous meta-analysis of bariatric surgery in adolescent subjects by Treadwell and colleagues [27].

230

D.A. Fitzgerald, L. Baur / Paediatric Respiratory Reviews 15 (2014) 227–230

PSYCHOLOGICAL CONSIDERATIONS Beyond the issues of weight loss, one must consider the adolescent as being in a psychologically vulnerable position. Obese adolescents in hospital based programmes have a high prevalence of psychopathology [29,30]. This impacts upon adherence with treatment and in part is seen as an advantage that surgery may offer by proponents of bariatric surgery [28,31,32]. One large Swedish study demonstrated that 93% of adolescents achieved >50% excess weight loss over 2 years following RYGB [28]. In this cohort of 81 patients who underwent RYGB surgery, the authors identified psychiatric or addictive problems in 12% of their cohort, all of whom were known to have psychiatric problems prior to surgery. From this same cohort, the authors reported on the psychological outcomes for the operative group which were favourable, but cautioned about the need for ongoing psychological support within the context of multi-disciplinary ongoing follow-up [33]. ETHICAL CONSIDERATIONS There is the valid concern raised by Hofmann [34] that health practitioners must be cautious not to ‘‘punish’’ children for the shortcomings of their parents in ‘‘allowing’’ their children to become so obese. Hofmann argues that bariatric surgery may be life-saving in some children but inappropriate for others based on their BMI alone. As with all interactions in complex paediatric and adolescent patients, decision making involves many issues beyond the physical presentation of the problem. Family engagement in decision making about bariatric surgery in adolescents is vital if long term outcomes are to be achieved successfully. CONCLUSION Bariatric surgery represents an attractive treatment option for a subset of severely obese adolescents for whom lifestyle change and ‘‘medical therapy’ has proven ineffective. There are concerns about the long term impact of surgery on metabolic outcomes and psychological issues. When one considers the alternatives of progressive co-morbidities, lack of mobility and engagement within society, persisting welfare dependence because of physical disabilities and a considerably elevated risk of earlier death, then the prospect of surgical treatment for severe obesity in adolescents merits close consideration. References [1] Finkelstein EA, Trogdon JG, Cohen JW, dietz W. Annual Medical Attributable to Obesity: Payer and Service Specific Estimates. Health Affairs 2009;28. w822–831. [2] Tsai AG, Williamson DF, Glick HA. Direct medical cost of overweight and obesity in the USA: a quantitative systematic review. Obes Rev 2011;12:51–60. [3] Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials. BMJ 2013;347:15934. http://dx.doi.org/10.1136/bmj.f5934 (Published 22 October 2013). [4] NHS Information Centre. Health Survey for England: Child Trend Tables. NHS Information Centre London, 2011. [5] Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among US children and adolescents. JAMA 2012;307:483–90.

[6] Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH. Cardiovascular risk factors and cardiovascular adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr 2007;150(12):e12–7. [7] The NS, Suchindran C, North KE, Popkin BM, Gordon-Larson P. Association of adolescent obesity with risk of severe obesity in adulthood. JAMA 2010;307: 483–90. [8] Ingelfinger JR. Bariatric Surgery in Adolescents. N Engl J Med 2011;1365–7. [9] Barlow SE, the Expert Committee. Expert Committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007;120(Suppl 4): S164–92. [10] August GP, Caprio S, Fennoy I, et al. Prevention and treatment of pediatric obesity: and Endocrine Society clinical practice guideline based on expert opinion. J Clin Endocrinol Metab 2008;93:4576–99. [11] Han JC, Lawler DA, Kimm SY. Childhood obesity. Lancet 2010;375:1737–48. [12] Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA 2003;289:187–93. [13] Oude Luttikhuis H, Baur L, Jansen H, et al. Interventions for treating obesity in children. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001872. http://dx.doi.org/10.1002/14651858.CD001872.pub2. [14] Ho M, Garnett SP, Baur L, et al. Effectiveness of lifestyle interventions in child obesity: systematic review with meta-analysis. Pediatrics 2012;130: e1647–71. [15] Dixon JB, Fitzgerald DA, Kow L, Bailey D, Baur LA. Adolescent bariatric surgeryANZ guidance and recommendations. ANZ J Surg 2011 Dec;81:854–5. [16] Baur LA, Fitzgerald DA. Recommendations for bariatric surgery in adolescents in Australia and New Zealand. J Paediatr Child Health 2010 Dec;46(12):704–7. [17] Black JA, White B, Viner RM, Simmons RK. Bariatric surgery for obese children and adolescents: a systematic review and meta-analysis. Obesity Reviews 2013;14:634–44. [18] Leifsson BG, Gislason HG. Laparoscopic Roux-en-Y gastric bypass with 2-metre long bilio-pancreatic limb for morbid obesity; technique and experience with the first 150 patients. Obes Surg 2005;15:35–42. [19] Kuzmak L. Silicone gastric banding: a simple and effective operation for morbid obesity. Contemp Surg 1986;28:13–8. [20] Baltasar A, Serra C, Pe´rez N, Bou R, Bengochea M, Ferri L. Laparoscopic sleeve gastrectomy: a multi-purpose bariatric operation. Obes Surg 2005;8:1124–8. [21] Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery for obesity. Cochrane Database of Systematic Reviews Issue 2. [http://dx.doi.org/10.1002/ 14651858.CD00364.pub3]. [22] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37. [23] O’Brien PE. Bariatric surgery: mechanisms, indications and outcomes. J Gastroenterol Hepatol 2010;25:1358–65. [24] Tsai WS, Inge TH, Burd RS. Bariatric Surgery in adolescents: recent national trends in use and in-hospital outcome. Arch Pediatr Adolesc Med 2007;161: 217–21. [25] Inge TH, Garcia V, Daniels S, et al. A multi-disciplinary approach to the adolescent bariatric surgical patient. J Pediatr Surg 2004;39:442–7. [26] Stefater M, Jenkins T, Inge T. Bariatric Surgery for adolescents. Pediatr Diabetes 2012;14:1–12. [27] Treadwell JR, Sun F, Scholles K. Systematic review and meta-analysis of bariatric surgery for pediatric obesity. Ann Surg 2008;248:763–76. [28] Olbers T, Gronowitz E, Werling M, et al. Two year outcome of laparoscopic Roux-en Y gastric bypass in adolescents with severe obesity: results from a Swedish Nationwide Study (AMOS). Int J Obesity 2012;36:1388–95. [29] Duffecy J, Bleil ME, Labott SM, Browne A, Galvani C. Psychopathology in adolescents presenting for laparoscopic banding. J Adolesc Health 2008;43: 623–5. [30] Britz B, Siegfried W, Zeigler A, et al. Rates of psychiatric disorders in a clinical study group of adolescents with extreme obesity and in obese adolescents ascertained via a population based study. Int J Obes Relat Metabol Disord 2000;24:1707–14. [31] Puzziferri N, Nakonezny PA, Livingston EH, Carmody TJ, Provost DA, Rush AJ. Variations of weight loss following gastric bypass and gastric band. Ann Surg 2008;248:233–42. [32] Widhalm K, Dietrich S, Prager G, Silberhummer G, Orth D, Kispal ZF. Bariatric surgery in morbidly obese adolescents: a four year follow up of ten patients. Int J Ped Obes 2008;3:S78–82. [33] Jarvholm K, Olbers T, Marcus C, et al. Short-term psychological outcomes in severely obese adolescents after bariatric surgery. Obesity (Silver Spring) 2012;20:318–23. [34] Hofmann B. Bariatric surgery for obese children and adolescents: a review of the moral challenges. BMC Medical Ethics 2013;14:18.