Metabolic and Bariatric Surgery in Adolescents: For Whom, When, and How? Open Access

Worldwide, almost one in five adolescents lives with overweight or obesity [1]. Obesity constitutes a critical risk for current and future physical health and impairs psychological and social well-being [2, 3]. More often than not, obesity will remain in adulthood [4]. The interplay of the genetic predisposition and environmental factors explains the individual patient’s weight trajectory, their risk of developing obesity-related complications, and the likely response to treatment [5, 6].

Cole and Lobstein determined cut-offs for defining obesity based on data from children from six countries for the International Obesity Task Force (IOTF) [7]. The IOTF-body mass index (BMI) definitions of overweight, obesity, and severe obesity are used extensively in Sweden. The terminology of class II and class III obesity was introduced later and is often used in relation to bariatric surgery. Class II obesity is defined as either an absolute BMI ≥35 kg/m² or the Centre of Disease Control (CDC) BMI ≥120% of the 95th percentile of BMI for age, whichever is lowest. For class III obesity, the cut-offs are an absolute BMI ≥40 kg/m² or BMI ≥140% of the 95th percentile of CDC-BMI for age [8‒10]. Severe obesity augments the challenges of increased BMI, while interventions based on lifestyle modification show limited effects among adolescents with severe obesity [11‒13].

Bariatric surgery, often referred to as metabolic and bariatric surgery (MBS), is a standard treatment for adult patients. The Swedish Obese Subjects (SOS) study has been pivotal in evaluating the long-term effects of bariatric surgery in adults, showing sustainable results on weight, improved lifestyle, and reduced risks of complications to obesity [14]. Similarly, a Scandinavian Obesity Surgery Registry for patients of all ages with very high coverage and a large cohort study in the USA contributed to the continued evaluation of bariatric surgery [15, 16]. Most bariatric surgery in Sweden is publicly funded and this may affect patient selection.

The mechanisms of action in bariatric surgery go beyond mechanical restriction of food intake and malabsorption. Miras and le Roux discussed the various mechanisms that contribute to weight loss after bariatric surgery without triggering the compensatory behaviours that usually oppose weight loss. Increased levels of gut hormonal satiety signals, glucagon-like peptide 1 (GLP-1) and peptide YY, and decreased levels of the appetite-stimulating ghrelin will help facilitate weight loss [17]. The effects of rapid stomach emptying, altered vagal signalling, insulin release, and gut microbiota may assist patients in making changes in food preferences and meal patterns, contributing to the effect of bariatric surgery [17] (Fig. 1).

Bariatric surgery has also been introduced as a treatment option for adolescents with severe obesity. However, the few existing guidelines on bariatric surgery for children and adolescents give somewhat different recommendations. The comprehensive guidelines on MBS in children and adolescents by the American Society for Metabolic and Bariatric Surgery (ASMBS) Pediatric Committee in the USA provide a review of existing data and robust advice. The ASMBS eligibility criteria for bariatric surgery stipulate class II obesity with comorbidity or class III obesity without comorbidity [10]. The comorbidities substantiating the indication are non-alcoholic liver steatosis, T2DM, obstructive sleep apnoea syndrome, cardiovascular risk factors, orthopaedic disease, physical impairment, gastro-oesophageal reflux disease, idiopathic intracranial hypertension, and low quality of life [10]. The 2014 National Institute for Health and Care Excellence (NICE) guidelines in the UK presented bariatric surgery as an option in “exceptional circumstances” [18], but updated indications mirror those of the ASMBS, suggesting bariatric surgery can be offered to patients with BMI 40 without comorbidities, BMI 35 with comorbidities, or in patients with BMI 30 who have new-onset T2DM [19].

In 2015, the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) suggested bariatric surgery as an option for adolescents who had achieved 95% of the expected height and a BMI ≥40 kg/m² with severe comorbidities and BMI ≥50 kg/m² with mild comorbidities [20]. The differences between guidelines have clinical consequences. The recent guidelines from the European Association for Endoscopic Surgery for bariatric surgery explicitly relate to adult patients only [21]. Although there are national guidelines under construction in Sweden, we are not aware of any other current European guidelines on bariatric surgery for adolescent patients.

Concerns around adolescent bariatric surgery can be attributed to a fear of side effects on growth and puberty, risk of nutritional deficiencies and osteoporosis, alcohol abuse, sustainability of weight loss, psychosocial vulnerability, and the ability to consent in the decision process [22, 23]. A practical reason for bariatric surgery often being overlooked within adolescent treatment frameworks is that it is predominantly performed by adult surgeons.

The World Health Organization defines adolescence as age 10–19 years [24] and the American Association of Pediatrics extends the upper age limit of adolescents to 21 years [25]. In this period of life, parental influence will diminish. The adolescent will gradually transition through the physical, social, and cognitive transformations and become an autonomous adult person [26]. For adolescents with a chronic disease, such as obesity, the natural challenges of adolescence will be affected by the disease. Previous struggles with overweight may have exhausted parental support and the crucial social interactions with peers, and school performance may be impaired [27]. Many adolescents with obesity have concomitant neuropsychiatric problems [28]. On the supply side, healthcare is often strictly divided into paediatric or adult care, necessitating the transition of patients at some point in late adolescence. In the adult care setting, the adolescent patient will often be much younger than the typical adult patient, and the special needs of the younger patients may be overlooked [29].

In this review, we present a non-structured review of published data on bariatric surgery in adolescents and add conceptual reflections from our experience of 15 years of bariatric surgery in adolescents with an almost complete follow-up. We aimed to contribute to the ongoing discussion on the “for whom, when, and how” of adolescent bariatric surgery [22, 23, 30], discuss programme requirements for the healthcare providers, and identify knowledge gaps requiring attention.

A few high-quality studies from the USA and Sweden on the effects of bariatric surgery in adolescents have presented long-term results (Table 1). In the Adolescent Morbid Obesity Surgery (AMOS) study, 81 adolescents underwent bariatric surgery with Roux-en-Y gastric bypass at a single surgical centre after inclusion at three specialized tertiary paediatric obesity clinics in Sweden [31]. At the 5-year follow-up, the patients had lost on average 36.8 kg, which was similar to matched adult controls. All metabolic risk factors were improved. Glucose homoeostasis was normal 5 years after surgery in 18 of the 22 patients who had disturbed glucose homoeostasis at the baseline. At a group level, fasting means plasma insulin levels decreased significantly, from 217 pmol/L at the baseline to 65 pmol/L at 5 years, and the fraction of patients with dyslipidaemia fell from 69% at the baseline to 15% at 5 years.

However, gastric bypass was associated with a need for additional surgical interventions in some patients, mostly laparoscopic procedures (bowel obstruction and cholecystectomy). Nutritional deficiencies were observed [32, 33]. Nine (11%) adolescent patients had long-term poor responses to bariatric surgery [31]. Following AMOS, AMOS2 was designed as a randomized controlled study of 50 adolescents between bariatric surgery and intensive non-surgical treatment. We noted an interesting sex difference with more eligible female patients willing to participate in AMOS2 [34]. The enrolment has ended, and the 2-year results of AMOS2 are expected in the near future.

Similarly, a weight loss of around 30% of the pre-surgery weight was demonstrated in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study in the USA of 161 adolescent patients. Interestingly, adolescent patients were significantly more likely to have remission of T2DM and hypertension than adults [35]. An analysis of 58 of the 74 patients in the Follow-up of Adolescent Bariatric Surgery (FABS) study in the USA showed durable weight loss, with a mean pre-surgical BMI of 58.5 kg/m² and follow-up BMI of 41.7 kg/m². Notably, two-thirds of patients remained at BMI 35 or higher [36]. The repeated observation of a weight loss of 25%–30% of pre-surgical weight [31, 35, 37] speaks in favour of not allowing pre-surgical weight to escalate but rather perform surgery earlier.

Lifestyle adaptations can serve as a foundation for promoting a positive outcome from bariatric surgery. Still, we argue that these lifestyle adaptations become easier to achieve for many patients as a result of surgery. Demanding a strict lifestyle adherence before surgery may discriminate against patients that are still likely to have a beneficial result of surgery. For adolescents, data suggest that adolescents who lose more weight pre-surgery will not necessarily respond best post-surgery [38]. However, there seems to be a higher divergence in the long-term weight outcome in adolescents compared to adults. In Teen-LABS, the proportion of patients that lost less than 5% of initial weight or increased in weight 5 years after surgery was significantly higher in the adolescent group [35].

Stigmatisation, psychosocial stress, and socio-economic disadvantages are more common in children and adolescents with obesity than in those with normal weight [28, 39‒41]. Many adolescents with severe obesity avoid situations and exposures when their weight would be a problem, which may aggravate the weight problem. These vicious circles may lead to social isolation and impaired educational achievements with profound life impact, and, in the extreme, a risk of never establishing an independent adult life [27]. For weight-related quality of life, the effects of weight loss can in part be accredited to the reduced body size. To fit into a seat when travelling by aeroplane, being able to use a safety belt in a car, go canoeing, to be able to be a standing passenger on a bus without blocking the aisle for others, and reduced joint and back pain are some of these benefits. During the first year after bariatric surgery, many adolescents experience improvements in health- and weight-related quality of life [42, 43].

Adolescence and young adulthood are periods of life with increased risk of the onset of mental health disorders [44] and psychiatric disease is more prevalent in adolescents with obesity than in normal-weight peers [45]. Thus, adolescents presenting for bariatric surgery represent a vulnerable group from a mental health perspective [42, 46]. For many adolescent patients, similar to outcomes in adults, there is a short-term reduction of mental health problems during the first years after bariatric surgery. In the AMOS study, symptoms of anxiety, depression, and self-esteem improved after bariatric surgery and participants achieved a level of mental health and self-concept comparable to norms for peers [43]. At the same time, one in five adolescents reported substantial mental health problems at the 2-year follow-up, and 14% reported suicidal ideation [46]. Baseline mental health problems were associated with poor mental health after surgery. Five years after surgery, few improvements in general mental health problems compared to the baseline were seen despite substantial weight loss [45]. However, self-reported problems with binge eating and uncontrolled eating were still improved 5 years after bariatric surgery compared to the baseline, indicating sustained improvements in eating-related problems several years after surgery [45].

It is essential to discuss with patients opting for surgery that some, but not all, problems may improve after surgery. Keeping a diary and taking notes as concerns are addressed during consultations may help patients go back and develop their own decision-making tree later. As noted above, general mental health problems will probably not improve and additional treatment is therefore often necessary [45, 47].

An experienced psychologist can evaluate autonomy, independence, ability to consider a long-term perspective, risk behaviours, and degree of family support. As in adults, the preoperative evaluation should include an assessment of general mental health and eating-related problems. In adolescents, it is important to include an evaluation of anxiety disorders and non-suicidal self-injury [44, 48]. Self-harm events are more common after bariatric surgery [49, 50], and those with a preoperative history are at higher risk [51].

Equally crucial in the preoperative assessment is to establish a long-term plan for follow-up of mental health to identify patients in need of additional interventions. While maintaining a therapeutic relationship during the first year after surgery is likely beneficial, the 2-year follow-up stands out as an important time-point to screen for persistent or new-onset mental health problems [46, 50]. Altered absorption and reduced body weight mandate careful attention to psychiatric medication after bariatric surgery [52]. During 5 years of follow-up in AMOS, 43% of the patients had one or more prescribed psychiatric drugs. Some of the most used medications for attention-deficit hyperactivity disorder, including methylphenidate and its derivatives, may need adjustment for the new body weight, both dosage and choice of short-acting or slow-release pharmaceuticals. Uptake may be affected in both directions following bariatric surgery [53, 54]. According to the ASMBS guidelines, low quality of life is an indication for bariatric surgery for patients with class II obesity, and a mental health disorder is not a contraindication for bariatric surgery in adolescents, except in cases with active psychosis, suicidality, or substance abuse [10].

Female patients with severe obesity risk both fertility problems and adverse pregnancy outcomes [55]. Women who underwent bariatric surgery before pregnancy had a reduced risk of gestational diabetes and pre-eclampsia and a reduced risk of large-for-gestational-age infants but an increased risk of small-for-gestational-age infants [56, 57]. Bariatric surgery can increase fertility and all female patients should be counselled on contraception to avoid unintended pregnancies [10].

An increased risk for substance abuse after bariatric surgery has been well described, with particular risk among male patients and those who consumed alcohol before surgery [58]. While the risk of substance abuse has been suggested to be lower after sleeve gastrectomy than after Roux-en-Y gastric bypass, other data suggest no difference in risk [59, 60]. An issue of concern in the Teen-LABS study was the death of two participants from the adolescent group, both associated with substance abuse [61]. The ASMBS guidelines recommend preoperative screening for alcohol use and to inform patients about the risks of developing substance abuse [10].

The ASMBS guidelines advocate an integrated approach where the Tanner pubertal stage and linear growth do not exclude patients from bariatric surgery [10]. In contrast, the NICE and the ESPGHAN guidelines consider bariatric surgery an option if the patients have achieved, or nearly achieved, physical maturity, or adult height [18, 20]. Recent data from 242 adolescents in the Teen-LABS cohort with an average BMI of 52.6 kg/m² demonstrated similar results for patients aged 13–15 years in comparison to patients 16–19 years of age, which supports the use of individual clinical indications rather than strict age limits [10, 37]. Until now, we have not suggested bariatric surgery until patients have reached Tanner 3 and peak height velocity. This practice may change into a more individualized approach as in the ASMBS guidelines [10].

For patients fulfilling the criteria for surgery, the timing of surgery should be addressed. The complications of severe obesity emerge slowly and are difficult to predict. In our clinical experience, few patients seem to perceive bariatric surgery as a “quick fix.” With guidance, most adolescents seem capable of comprehending the dimensions of the decision they are about to make. In the AMOS2 study, many eligible patients were unwilling to be randomized to either bariatric surgery or non-surgical intensive treatment, the most common reasons stated as being “not interested” and considering surgery “too drastic” [34]. In the absence of reliable predictors for a good outcome, we encourage a slight shift from efforts trying to accurately predict the outcome to providing tailored support for patients after surgery in order to optimize their individual outcome (Fig. 2).

Qualitative research has shown a range of motivations among adolescents opting for bariatric surgery, such as a wish to stay healthy, be “normal” and as a way forward when all other non-surgical options have failed [62]. We emphasize self-reflection, self-efficacy, and ownership, and encourage empowering and constructive reflections, such as: “What are my strengths and what can I do to put myself in a position to get the most out of surgery if I chose it? What would be the risks? What support do I need? When would be the best time in my life? How can I be at a lower, not a higher, weight at surgery?”

Our clinical impression is that patients who are hesitant to make other lifestyle adaptations and see bariatric surgery as the only means to help them may not be ready for the intervention. Previous disappointments, lack of knowledge, lack of power or support, or psychiatric diagnoses may contribute to the patients locking their views on bariatric surgery. The relevance of the pre-surgery weight for the result on weight needs to be discussed and it is essential not to give the patient the false impression that they are more likely to “get” bariatric surgery the heavier they become. Instead, we value compliance to appointments and praise all attempted lifestyle changes and efforts to join activities. Patients not participating in regular daily activity, school, or work, are encouraged to establish such structure before surgery, as we find a daily structure is associated to a positive postoperative outcome. We also encourage routines for food and exercise that mimic the advice for life post-surgery. Social services are sometimes consulted, for adolescents who have abandoned school or are unemployed, to help with providing training or job positions. We have seen that an existing social network might often be more likely to be in place at ages 16–18 years and secondary school than a few years later, which also becomes an argument for not postponing surgery.

Eating disorders should be screened for when considering bariatric surgery. The diagnosis of the most common eating-related problem, loss-of-control eating, is challenging as many patients with severe obesity will report occasions when they have eaten much more than they intended [63]. The psychologist should use instruments adapted for teenagers for assessing eating behaviours. Eating disturbances are not an absolute contraindication [10]; however, compensatory behaviours, such as vomiting, require treatment and control before referral to bariatric surgery. Some adolescents report strong emotional components of their eating. They should be offered help to develop other strategies for emotional regulation before bariatric surgery and establish a reasonably adequate meal structure pre-surgery.

Many patients with obesity-associated genetic syndromes develop a degree of obesity that becomes a significant limitation to their physical and social well-being. For patients with a hypothalamic component of hyperphagia, like Prader-Willi syndrome, bariatric surgery has shown limited results and remains debated [64‒66]. In other syndromes, bariatric surgery and the resulting weight loss may greatly add to the patient’s quality of life. Interventions in patients with limited autonomy warrant ethical considerations [67]. If a patient with age-relevant autonomy would have been eligible for surgery, it can be regarded ethically correct to consider a patient with impaired autonomy as well, not to discriminate against the patient with limited autonomy. This attitude is supported by the ASMBS guidelines: “When a child does not have the decisional capacity, but is able to demonstrate the ability to make lifestyle changes required by metabolic and bariatric surgery with or without the assistance of a dedicated caregiver, then metabolic and bariatric surgery should be considered” [10].

Recently, GLP-1 analogues have shown promising effects for treating obesity. In a randomized controlled trial of weekly injections of semaglutide for adult patients with a mean BMI of 38 kg/m², 7 out of 10 patients lost at least 10% of their initial weight. One-third of patients lost 20% of baseline weight [68]. This result is in the vicinity of bariatric surgery in terms of weight loss, but not in the proportion of patients achieving this degree of weight loss. A randomized study on adolescents showed a significant but more modest effect of daily injections of liraglutide with 26% of treated patients, and 8% of controls, achieving a 10% BMI loss at 56 weeks follow-up. Unlike for bariatric surgery, metabolic parameters were not improved in the study [69]. The long-term effects of GLP-1 analogues in adolescents with severe obesity remain to be elucidated.

GLP-1 analogues may not be able to achieve the strong and sustainable results of bariatric surgery. Still, the GLP-1 analogues have limited side effects and constitute an attractive and reversible addition to the limited therapeutic toolbox for treating obesity. GLP-1 analogues can also serve as an attractive bridge to, and maybe from, bariatric surgery.

The two most commonly performed bariatric surgical procedures are Roux-en-Y gastric bypass and sleeve gastrectomy [70]. Almost always, the procedure is performed laparoscopically. For a long time, Roux-en-Y gastric bypass was the method of choice in adolescent patients, as evident within the studies discussed above [31, 35, 36, 70]. In a Roux-en Y gastric bypass, the stomach is “bypassed,” with a loop of jejunum anastomosed to a small pouch of the proximal stomach. Ingested nutrients will thus bypass most of the stomach, the duodenum, and the proximal jejunum [17]. The procedure is feasible to reverse, although rarely without some residual effects.

In a sleeve gastrectomy, a majority of the stomach is resected on its greater curvature and removed creating a tube-like remnant stomach [17]. Sleeve gastrectomy has been considered a less radical procedure and its popularity has increased to become the most common procedure, both in adults and adolescents [70]. However, long-term efficacy and safety remain to be demonstrated in adolescents [10, 23]. The risk of gastro-oesophageal reflux after sleeve gastrectomy and the potential development of chronic oesophagitis and even the evolution to Barrett’s oesophagus and dysplasia may be of particular relevance to younger patients with a long-estimated lifespan [71]. Sleeve gastrectomy is not reversible but can be revised into a gastric bypass. A third method, the adjustable gastric band procedure, has become less popular and is no longer used in Sweden. The risk for long-term nutritional deficiencies appears similar following sleeve gastrectomy and Roux-en-Y gastric bypass [31, 36], and patients require life-long supplements of vitamin B12, iron, and calcium after both procedures.

In our clinical experience, Roux-en Y gastric bypass has been the most used procedure. An important aspect of the choice of method is that many patients will have personal experiences in their extended family and express preferences on which method to use. In the AMOS2 study of 50 adolescents opting for bariatric surgery, 21 (41%) had at least one parent who had undergone bariatric surgery [34]. There is an urgent need for well-designed trials to guide the choice of procedure, comparing the outcomes of Roux-en Y gastric bypass and sleeve gastrectomy in adolescents.

The existing guidelines give limited advice on the follow-up of adolescent patients after bariatric surgery [10, 18, 20]. Results from structured follow-up within research studies have influenced the clinical care of adolescent patients in our clinical practice. In Sweden, adult patients are routinely seen at the surgical clinic at 6 weeks, 1 year, 2 years, and 5 years after surgery. Patients are usually referred for annual check-ups at their primary care physician 1 or 2 years after surgery. In contrast, adolescent patients are offered visits to various professionals in the paediatric obesity team, including the child psychologist, often amounting to 6–12 times per year. At these visits, the obesity team members encourage the rapid weight loss as some adolescents are unnerved by the pace the weight is lost, discuss eating behaviour, and advocate for a regular meal structure. We initially aim for 6–8 meals per day and gradually try to encourage a structure of three main meals and two snacks. We advise on suitable foods and encourage adequate fluid intake, evaluate cardio-respiratory fitness, encourage physical activity, discuss social, and psychological effects of the weight loss, and encourage compliance with the prescribed life-long supplements of iron, vitamin B12, calcium, and multivitamins. We support the patient in recognizing and reflecting on dumping syndrome and the risk of hypoglycaemia, for example, when starting driving lessons, and stress the importance of seeking care in case of abdominal pain.

Bone quality is of crucial importance for adolescents after bariatric surgery and Dual-Energy-X-ray provides important information on bone mineral density over time [33]. We discuss alcohol use and provide referrals for contraceptives. A great concern for many patients is the surplus skin that also young patients can develop after successful weight loss [72]. A few patients may be eligible for abdominoplasty due to surplus skin, but only once their weight has stabilized, usually after 2 years.

A rapid weight loss of around 25%–30% of pre-surgical weight is usually seen during the first 12–18 months after bariatric surgery [31, 35‒37]. Successful adolescent patients may find follow-up visits less important during this first year and need to be encouraged to come. By making efforts to maintain patient contact, health providers can help the adolescent patient achieve substantial weight loss in the first year after surgery and seek to prevent later failure or complications. Web-based support and digital healthcare maybe even more suitable for adolescents after bariatric surgery.

The challenges of evaluating adolescents with severe obesity for bariatric surgery and following patients after surgery are best handled in multi-professional teams [10]. Arenas for collaboration with practitioners from adult and paediatric surgery and paediatrics need to be identified. In clinical care, an individualized assessment is performed for patients who are considered eligible for bariatric surgery and are interested. Evaluations are conducted by a paediatrician, a physiotherapist, a dietician, and a psychologist, and a specialized paediatric nurse serves as the coordinator. Team conferences are held. A 2–4-week low-calorie diet is a standard treatment prior to surgery [73] and patients need intense support from a dietician. We argue for centralization of decision-making to specialized and dedicated centres and highlight the need to overcome issues of transition into adult care [74]. The ASMBS recommends that all adolescents with severe obesity be referred, early, to MBS programmes that are established for adolescents [10].

We have developed a multi-professional National advisory network for treating adolescents with severe obesity. In monthly Web-based meetings, patients that have been proposed for bariatric surgery are discussed. In addition to previous and ongoing studies, these multi-professional conferences have contributed significantly to the structured investigations, equality, and safety of adolescents’ bariatric surgery in Sweden [74]. A timeline for evaluating adolescent patients for bariatric surgery, interventions, and follow-up in Sweden is shown in Figure 3.

MBS should be a considered standard of care for adolescents with severe obesity, yet existing guidelines vary. A multi-professional team should guide the preoperative workup, and the timing of bariatric surgery in the young person’s life needs careful consideration. The level of pre-surgery weight is of great importance to the outcome, and we argue for not delaying surgery uncertainly.

Factors predicting a good outcome after bariatric surgery are incompletely understood, and we suggest a shift to optimizing outcomes during follow-up. Centralization of pre-surgical investigations, surgical interventions, and follow-up to a limited number of specialized multidisciplinary teams may be advantageous, as per international guidance.

Future studies should assess long-term outcomes, outcomes in younger adolescents and patients with syndromic obesity. Additionally, the role of pharmacological treatments, such as GLP-1 analogues, and outcomes after various surgical techniques need further investigation in adolescent patients.

A. Janson has no conflict of interest to declare. K. Järvholm has received speaker honorariums unrelated to the submitted article from Novo Nordisk. K. Järvholm has also been on an advisory board unrelated to the submitted article for Novo Nordisk and reimbursements were directed to her clinical institution. J. Dahlgren has no conflict of interest to declare. L. Sjögren has no conflict of interest to declare. A.J. Beamish participated in education provision for Johnson & Johnson, unrelated to the submitted paper, for which an educational honorarium was awarded. E. Gronowitz has no conflicts of interest to declare. T. Olbers participated in advisory boards for Johnson & Johnson and Novo Nordisk unrelated to the submitted paper, and reimbursements were directed to his academic institution.

This study has no specific funding.

A.J. drafted the review. All the authors contributed in conceptualizing the review, the writing process, and accepted the final version of the manuscript.