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Michael A. Helmrath, MD,Mary L. Brandt, MDa,
aMichael E. DeBakey Department of Surgery, Baylor College of Medicine,
Texas Children’s Hospital Clinical Care Center, Suite 650, 6621 Fannin,
Division of Pediatric General and Thoracic Surgery,
Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue,
Obesity has become the most common nutritional disorder of children
and adolescents in the United States. Along with this epidemic, there hasbeen an increase in associated potentially life-threatening diseases. TheWorld Health Organization classiﬁcation in adults deﬁnes overweight asa body mass index (BMI) of 25 to 30 kg/m2 and obesity as a BMI of30 kg/m2 or more. The BMI, which takes into account the relationship ofweight and height, correlates with the amount of body fat in children andadults In children, the ratio of weight to height changes with growth.
For that reason BMI growth charts have been developed for children bythe US Centers for Disease Control and Prevention. The deﬁnition ofobesity for children is ninety-ﬁfth percentile or more of BMI for age.
Children with a BMI between the eighty-ﬁfth and ninety-ﬁfth percentileare considered overweight . Using these criteria, the prevalence of beingobese doubled among children aged 6 to 11 years and tripled amongchildren aged 12 and 17 years in the United States between 1980 and2000. Currently more than 1 million adolescents and young adults in theUnited States are considered severely obese (BMI R40 kg/m2). Groupsthat are at particularly high risk for morbid obesity include AfricanAmericans, Hispanics, Pima Indians, and other Native Americans.
The epidemic of obesity has multiple causes. Human beings are
genetically predisposed to store fat, a survival mechanism that served wellduring lean times for our prehistoric ancestors. Currently our lifestyles,unlike those of our ancestors, are much more sedentary. Food in modern
* Corresponding author.
E-mail address: (M.A. Helmrath).
0039-6109/06/$ - see front matter Ó
2006 Elsevier Inc. All rights reserved.
society also is plentiful, processed, and energy dense. In general, it is thoughtthat genetic predisposition plays a permissive role, interacting withenvironmental factors to promote obesity. It is estimated that 30% to50% of the tendency toward excess adiposity can be explained by geneticvariations Although numerous genetic markers are linked with obesityand its metabolic consequences, identiﬁable hormonal, syndromic, or molec-ular genetic abnormalities are present in less than 5% of obese individuals. More than 430 genes, markers, and chromosomal regions have beenassociated or linked with human obesity phenotypes Every chromosome,except the Y chromosome, has a locus linked with the phenotype of obesity.
The most frequent mutations that result in the obesity phenotype have beenfound in the melanocortin receptor 4, occurring in up to 4% of early-onsetand severe childhood obesity Given recent genetic ﬁndings, it is highlyprobable that severe childhood obesity is polygenic, with susceptibilityconferred via complex interactions among genetic factors, behavioralfactors, and the environment.
Obesity in many children is not a problem of ‘‘willpower’’ or ‘‘discipline’’
but is a potentially life-threatening disease. A dose-response relationshipbetween BMI during young adulthood and the risk of death has been dem-onstrated, with extreme obesity resulting in a reduction of 20, 13, 5 and 8years of life expectancy for black men, white men, white women, and blackwomen, respectively . Importantly, the loss of 5% to 10% of body weightresults in a signiﬁcant improvement of risk and comorbidities
Over the past decade, an alarming increase in the appearance of type 2
diabetes in children has occurred. Type 2 diabetes is responsible forapproximately one ﬁfth of the new diagnoses of diabetes in pubertalchildren. By some estimates, up to one third of all children and halfof Hispanic and black children develop type 2 diabetes in their lifetime. Diabetes can be diagnosed by a fasting plasma glucose O125 mg/dLin the presence of diabetes symptoms or two fasting plasma glucosevalues O125 mg/dL in the absence of symptoms or by measuring a serumglucose concentration O200 mg/dL 2 hours after an oral load of 75 g ofglucose (oral glucose tolerance test).
In adults, the metabolic syndrome is deﬁned by the US National
Cholesterol Education Program’s Adult Treatment Panel III as requiringthree of ﬁve characteristics:
1. Abdominal obesity with a waist circumference more than 102 cm in men
2. Triglyceride concentration O150 mg/dL or 1.7 mmol/L
3. Abnormal cholesterol proﬁle with high-density lipoprotein cholesterol
!40 mg/dL or 1 mmol/L in men and !50 mg/dL or 1.3 mmol/L inwomen
4. Blood pressure O130/85 mm Hg5. Impaired fasting glucose R100 mg/dL or 5.5 mmol/L
The metabolic syndrome is a clustering of risk factors for later cardiac
disease and diabetes. Approximately 47 million adults meet criteria forthis syndrome, which elevates one’s risk of later heart diseases twofoldand the risk of diabetes ﬁvefold. There is as yet no deﬁnition of metabolicsyndrome for the pediatric age group, but using the adult criteria, the overallprevalence of metabolic syndrome among 12- to 19-year-old individuals inthe United States was found to be 4.2% Using modiﬁed criteria, Weissand colleagues found that nearly 50% of severely obese adolescents metcriteria for the metabolic syndrome and that the risk increased as BMIincreased. Currently, there is a lack of certainty about the pathogenesis ofthe syndrome, and considerable controversy exists about whether themetabolic syndrome poses a greater health risk than the sum of its parts,especially for pediatric patients.
Acanthosis nigricans, another frequent manifestation of insulin resistance,
is characterized by hyperpigmented, hyperkeratotic, velvety plaques on thedorsal surface of the neck and hands. Insulin resistance also stimulatesovarian and adrenal androgen and estrogen production. These hormonalperturbations place obese adolescent girls at high risk of menstrual disordersand early onset of polycystic ovary syndrome. Polycystic ovary syndrome,previously called Stein-Leventhal syndrome, is a complex metabolic diseasethat may present in adolescents and is associated with obesity. Thissyndrome is manifested by oligomenorrhea or amenorrhea associated withobesity, insulin resistance, hirsutism, acne, and acanthosis nigrans . Itis reasoned that weight loss, which results in decreases in insulin resistance,can be an important adjunct to treatment of polycystic ovary syndromeand menstrual abnormalities in obese patients
Cardiac risk factors are common in obese children and include
atherogenic dyslipidemia (low high-density lipoprotein cholesterol andelevated triglycerides or low-density lipoprotein cholesterol), hypertension,sleep apnea, and left ventricular hypertrophy. Fifty percent of overweightadolescents have one risk factor for developing cardiovascular disease and20% have two factors Childhood obesity is the leading cause ofpediatric hypertension. Systolic blood pressure correlates positively withBMI, skinfold thickness, and waist-to-hip ratio in children and adolescentsClinical hypertension is ten times more common in obese children thanlean children, with up to 30% of obese children having elevated systolic ordiastolic blood pressure . Signiﬁcant, irreversible consequences of
hypertension, such as hypertensive cardiac disease, can present in childhood.
In one study, 38% of children who had hypertension had left ventricularhypertrophy by echocardiography Others have noted that theprevalence of left ventricular hypertrophy increases as a function ofoverweight, with 3% of normal weight, 25% of overweight, 52% of obese,and 86% of morbidly obese youth fulﬁlling echocardiographic criteria forleft ventricular hypertrophy (Thomas Kimball, MD, personal communica-tion, 2005). Hyperlipidemia in obese children is most often manifested byelevated low-density lipoprotein cholesterol, elevated triglycerides, anddecreased high-density lipoprotein cholesterol .
There is a strong association between obesity and obstructive sleep apnea
syndrome (OSAS), because obese children are four to six times more likelyto have OSAS when compared with lean subjects Symptoms of OSASmay include snoring, poor school performance because of daytimesleepiness, enuresis, and hyperactivity . OSAS is diagnosed by anovernight sleep study to measure the apnea-hypopnea index. Twenty-sixpercent to 37% of obese children have an abnormal sleep study, althoughnot all have signiﬁcant obstruction . We have found that OSAScorrelates directly with BMI: 40%, 50%, and 70% of adolescents withBMI of 40 to 49, 50 to 59, and O60, respectively, meet polysomnographiccriteria for OSAS . For obese children, weight reduction improvesobstructive sleep apnea, although it is important to rule out other anatomiccauses of sleep apnea, such as tonsillar hypertrophy Obese chil-dren with sleep disorders may beneﬁt from an evaluation by anotorhinolaryngologist.
Obesity is related to a spectrum of liver abnormalities, referred to as
nonalcoholic fatty liver disease. This disease may present as isolated fattyinﬁltration of the liver to steatohepatitis (termed ‘‘NASH’’ for nonalcoholicsteatosis/hepatitis) or may involve ﬁbrosis and cirrhosis. Up to 40% ofobese children have ultrasound ﬁndings that suggest inﬁltration of the liver,and up to 40% of these children also have abnormal liver function testresults . Because characteristic biochemical ﬁndings do not alwayscorrelate with histology, diagnosis requires a liver biopsy Nonalcoholicfatty liver disease has been diagnosed histologically in up to 50% of obesechildren and in 83% of morbidly obese teenagers . Nonalcoholic fattyliver disease in childhood may be characterized by a benign clinical coursewithout progression. With escalating rates of pediatric obesity, however,there is concern that the prevalence and severity of NASH also may increasebecause of earlier and prolonged exposure to obesity and associated
inﬂammation . The long-term outcome of untreated NASH acquired inchildhood is unknown, but the literature notes that 25% of adult patientswho have NASH develop cirrhosis Currently, antioxidants are beingused for the treatment of NASH, but weight loss may prove to be theonly eﬀective treatment for nonalcoholic fatty liver disease .
Overweight children are susceptible to developing orthopedic problems.
Excess weight may cause injury to the growth plate and result in slipped cap-ital femoral epiphysis, genu valga, tibia vara (Blount’s disease), ﬂat kneecappressure/pain, spondylolisthesis, scoliosis, and osteoarthritis . Blount’sdisease (tibia vara) is overgrowth of the medial aspect of the proximal tibialmetaphysis, which occurs in response to and then accentuates bowing of thelegs under the pressure of excess weight .
Pseudotumor cerebri is a rare disorder characterized by a gradual
increase in intracranial pressure, which, if untreated, may result in visualimpairment or even blindness. The usual presentation is headaches, butpatients also may experience dizziness, unsteadiness, or diploplia Approximately 50% of children who have pseudotumor cerebri are obeseThere is no eﬀective long-term therapy other than weight loss .
Although not a life-threatening comorbidity, morbid obesity has a
profound impact on normal adolescent development. In a recent study,Schwimmer and Varni demonstrated that the health-related quality of lifeexperienced by obese children and adolescents was the same as that ofchildren undergoing chemotherapy for cancer The challenge ofadolescence is to make the transition to an emotionally and physicallymature adult who is able to work and have meaningful relationships Obese children are more at risk for poor self-esteem, withdrawal from socialinteraction, depression, and anxiety The impact of peer teasing andchanged body image can be profound in adolescents Among severelyobese adolescents, 48% have moderate to severe depressive symptoms and35% report a high level of anxiety. Extreme obesity is associated with an in-creased risk of suicide and suicidal ideation among adolescents Thisis particularly true for obese adolescent girls . Obese adolescents aremore likely to remain unmarried, have lower incomes, and live in povertythan their matched normal weight controls They are less likely to beaccepted into college than normal weight adolescents with comparablescholastic achievement
Treatment of morbid obesity in adolescence
Without question, obesity results from an imbalance in energy intake and
expenditure. The ideal treatment for obesity involves decreasing caloricintake while increasing caloric expenditure through exercise or nonexercisethermogenesis. Successful weight loss and maintenance require great eﬀortand commitment but are occasionally possible. In general, patients whoare successful in keeping weight oﬀ long-term exercise consistently, eatbreakfast regularly, control portions and fat in their diet, monitor theirweight, and eat consistently during weekdays and weekends . Althoughweight loss success is possible, most studies have shown that behaviormodiﬁcation and dieting are associated with poor weight loss, high attritionrates, and a high probability of weight regain For morbidly obeseteenagers with comorbidities, failure in one of these programs leaves littlechance to achieve and maintain a healthy weight into adulthood.
Behavioral and dietary measures have formed the cornerstone of
treatment of obesity . The abundance of diet books and programsavailable in our society reﬂects how ineﬀective most of these strategies arefor adults, however. It is not surprising that 90% to 95% of adult patientswho lose weight with dietary changes alone regain the weight. The lack ofeﬀective weight loss programs has intensiﬁed the ongoing search for eﬀectiveand safe medications to aid in weight loss Currently, the onlyanorectic agent currently approved for use in obese adolescents (olderthan age 16) is sibutramine, a nonselective inhibitor of serotonin,norepinephrine, and dopamine. When combined with caloric restriction,exercise,
sibutramine has been shown to be eﬀective in the treatment of adolescentobesity. In a prospective, randomized trial of 60 adolescents, the grouptreated with sibutramine had an average weight loss of 10.3 kg comparedwith 2.4 kg in a placebo group Although previous trials had reportedhypertension as a signiﬁcant side eﬀect, this was not a problem in this trial.
Orlistat also has been studied in the treatment of morbid obesity. Orlistat
inhibits pancreatic lipase and increases fecal losses of triglyceride. In theUnited States, the Food and Drug Administration has approved orlistatin children older than age 12. In a 1-year, prospective, randomized trial of539 adolescents, orlistat resulted in an improvement in weight controlcompared with a control group. BMI in patients on orlistat decreased by0.55 compared with an increase of 0.31 in the control group, a statisticallysigniﬁcant change but of no real clinical relevance Durable weightloss with orlistat requires maintenance of therapy; unfortunately, high studydropout rates occur because of unacceptable ﬂatulence and diarrhea .
Metformin is a bisubstituted, short-chain hydrophilic guanidine derivativethat activates AMP protein kinase and reduces fasting and postprandialinsulin concentrations. It has been used primarily in obese adolescents
who have polycystic ovarian syndrome to decrease weight and insulinresistance In preliminary studies, it also has improved obesity-relatedNASH Metformin is fairly well tolerated and is approved by the USFood and Drug Administration for the treatment of type 2 diabetes. It isnot approved for the treatment of childhood obesity.
Resorting to surgery to change the metabolism of a growing child is a
profound new concept, but adolescents with morbid obesity who havelife-threatening comorbidities probably warrant such a radical therapy.
Ethically, it is important that all adolescents ﬁrst be treated with aggressivenonoperative approaches and, once surgery is considered, that theindications for surgery are considered carefully. The indications for bariatricsurgery in adults were derived by an National Institutes of Health consensuspanel in 1991 based on known risks factors of obesity and its associatedcomorbidities . In general, adults with a BMI O40 with or withoutcomorbidities and BMI O35 with comorbidities who have failed multipleattempts at medical management of their obesity are considered candidatesfor bariatric surgery. This panel speciﬁcally avoided making a recommenda-tion for the treatment of patients younger than 18 years of age. Objectivedata to demonstrate the medical risk of being severely obese as anadolescent and carrying that obesity into adulthood would provideimportant insight required for developing objective criteria for this uniqueset of patients. In the absence of these data, the question remains: Willany adolescent patients beneﬁt from bariatric surgery? A task forceconvened by the American Pediatric Surgical Association addressed thisissue, taking into account the noncompliant nature of this population ofpatients, nutritional and developmental requirements, the ethical issue ofassent versus consent in children younger than age 18, and the overalllack of medical data supporting the role for bariatric surgery in severelyobese adolescents. The indications for surgery described by this task forceare much more conservative than those for adults and include the necessityof studying these patients for long-term outcome
Adolescents being considered for bariatric surgery require careful
preoperative testing and preparation. Preoperative testing should focus onidentifying comorbidities associated with severe obesity. Routine screeninglaboratories often performed on patients being evaluated for bariatricsurgery include a complete blood count, liver proﬁle, lipid proﬁle, fastinginsulin and glucose, oral glucose tolerance test at baseline, and vitaminB1, B12, and folate levels. All patients undergo a sleep study and ultrasoundevaluation of the abdomen to look for steatohepatitis, gallstones, and,in girls, ovarian pathology. In addition to a structured clinical interviewwith an adolescent psychologist, objective tests are performed to assess
personality traits, cognitive maturity, depression, eating behaviors, andweight-related quality of life, which may have a bearing on candidacy forbariatric surgery or postoperative adherence to medical and nutritionalregimens. Screening evaluation of all patients by a pediatric dietitian andexercise physiologist who have experience with adolescent obesity hasbeen helpful preoperatively and postoperatively. Participation in a monthlyadolescent support group is also required as part of the preoperativepreparation.
A multidisciplinary adolescent bariatric review board should deliberate
indications and contraindications before scheduling an adolescent for bari-atric surgery. Such a board should consist minimally of a medical director(pediatrician), surgical director (bariatric surgeon), pediatric psychologist,anesthesiologist, gynecologist, dietician, and ethicist. Such a board hasbeen developed at Cincinnati Children’s and Texas Children’s Hospital. Ithas facilitated the development of the adolescent bariatric programthroughout the hospital and community and been instrumental in resolvingpotential controversial patient selection and management decisions.
All patients are told that the long-term consequences of bariatric surgery
in adolescents are not known and that a long-term study of outcomes is anintegral part of this surgery. All patients who undergo surgery are asked toparticipate in a 10-year outcome study. Operative consent for surgeryincludes requiring all patients to write a letter describing their indicationsfor having a bariatric procedure, the short- and long-term risks of havingthe procedure, dietary restrictions and expectations, need to adhere tomedical and exercise regimen, their understanding of the procedure, andthe lifelong commitment that comes with the decision. The patient and par-ents/guardians are required to sign the letter and a formal operative consent.
Gastric bypass is considered the gold standard obesity surgery and is the
most commonly performed operation worldwide for obesity. Gastric bypasscan be performed by laparotomy or laparoscopy. Recent data suggestedthat the laparoscopic technique may have some advantages over the opentechnique, but only surgeons with advanced training and expertise inlaparoscopic and bariatric surgery should perform it . Laparoscopicgastric bypass surgery results in consistent initial weight loss in O90% ofpatients. Expected weight loss after laparoscopic gastric bypass surgery is20 to 30 pounds in the ﬁrst month and approximately 10 pounds/mo untilthe weight loss plateaus after 12 to 18 months. Preliminary data from ado-lescents demonstrated a decrease of BMI from 59 kg/m2 to 38 kg/m2 by1 year If a patient complies with the postoperative diet and exerciseprogram, a weight loss of 80% of excess body weight can be expected at 1year. Recidivism in the form of weight gain occurs in 20% to 30% of adults.
Durable weight loss occurs in most adolescents, yet up to 15% of these pa-tients may have late weight regain More important than the speciﬁcweight loss, laparoscopic gastric bypass surgery results in reversal of nearlyall studied comorbidities, with marked improvement in patient health and
long-term prognosis Treatment of morbid obesity with surgery re-sults in improved educational and occupational status
The ultimate success of all bariatric procedures depends on a patient’s
ability to adhere to a markedly changed and reduced diet. Given thepropensity of adolescents to rebel against strict regimens, continued supportmust be available to all of these patients. Postoperative vitamin and mineralsupplementation is critical and commonly consists of two pediatric chewablemultivitamins, a calcium supplement (1500 mg calcium citrate/d), andsupplementation of B-complex vitamins based on postoperative serumlevels. All nonsteroidal anti-inﬂammatory medications should be avoided.
Long-term nutritional complications can be avoided by the patient’sadherence to the ﬁve basic rules: (1) Eat protein ﬁrst. (2) Drink at least 64ounces of liquids daily. (3) No snacking between meals. (4) Walk or exerciseat least 30 minutes per day. (5) Always remember vitamins and minerals.
Early complications occur in 1% to 5% of patients who undergo
a laparoscopic gastric bypass surgery and include death, acute gastricdistention, pulmonary embolism (1%–2%), anastomotic leak (1%–2%),and wound infection (1%–5%) . The mortality rate associated withgastric bypass is 0.5% to 1% in most reports. Population-based datafrom Washington suggest a mortality rate of up to 6% during a surgeon’sﬁrst 20 bariatric procedures, decreasing to less than 0.4% beyond 100procedures performed . Acute gastric distention usually presents withhiccups, bloating, and left shoulder pain and is diagnosed by abdominalradiograph and ultrasound or CT scan demonstrating a dilated stomach.
Diﬀerentiating this condition from a jejunojejunostomy anastomoticobstruction is important and often requires an experienced radiologist orbariatric surgeon to interpret the radiologic ﬁndings. Acute gastricdistention may be treated by image-guided needle decompression, usuallyperformed by an interventional radiologist. If distention recurs, an image-guided percutaneous gastrostomy tube can be placed. The diagnosis of ananastomotic leak in the early-postoperative period is diﬃcult in obesepatients who may not manifest peritoneal signs. To further complicatematters, an upper gastrointestinal series may not demonstrate the leak.
The procedure of choice to evaluate a postoperative bariatric patient whohas unexplained tachycardia, particularly in the presence of fever, shoulder,or pelvic pain, should be surgical re-exploration.
Late complications of laparoscopic gastric bypass surgery include
anastomotic strictures, marginal ulcers, bowel obstructions from internaland incisional hernias, cholelithiasis, and dietary complications. Patientswho have internal hernias often present with recurrent periumbilicalabdominal pain or biliary colic in the absence of gallstones as their onlysymptom. Plain ﬁlms and upper gastrointestinal scans are often normal,whereas a CT may demonstrate dilation of the biliary limb but also maybe normal. The presence of persistent periumbilical pain, even in the faceof normal imaging studies, mandates exploration Patients who have
postprandial vomiting after bariatric surgery are at risk of developing dryberiberi, which most often presents with numbness in the extremities andataxia. If left untreated, the patient may develop irreversible encephalopathy. Previously, as many as 38% of adult obese patients who underwentbariatric surgery developed postoperative cholelithiasis. This number can bereduced substantially by prophylaxis with ursodeoxycholic acid therapy. Although previously a concern, the weight loss associated with bari-atric surgery does not aﬀect the outcome of subsequent pregnancies, as longas the mother has achieved a stable weight. For that reason, pregnancy iscontraindicated in the ﬁrst 1 or 2 years after surgery
Other surgical options exist for the treatment of morbid obesity in adults.
One of the more popular approaches is the laparoscopic gastric band, whichwas approved in the United States for use in adults in 2001 but has beenperformed around the world since the early 1990s. The adjustable gastricband oﬀers an enticing alternative to the gastric bypass because it ispotentially reversible and carries a lower morbidity and mortality rate(0.1%) The adjustable gastric band or ‘‘lap band’’ is a prosthetic bandwith an adjustable inner diameter that is placed around the proximal stomach,which restricts food intake. An adjustable gastric band is connected toa subcutaneous port, which is accessed via a needle through which salinesolution is injected to alter the inner diameter. The laparoscopic gastricband has been reported to be successful in European and Australian trials. These trials have yet to be reproduced in the United States, most likelybecause of the diﬀerence in abilities to provide week-to-week postoperativeadjustments and follow-up. Weight loss with an adjustable gastric bandoccurs more slowly than with other procedures, with maximal loss occurring2 to 3 years postoperatively, compared with 12 to 18 months in gastric bypass.
Complications of gastric banding include exacerbation of gastroesophagealreﬂux, esophageal dilation and dysmotility, and mechanical failure of portor device. Complications leading to reoperation have been reported in upto 41% of patients .
Morbid obesity in the United States has reached epidemic proportions.
Families, physicians, and the government are ﬁnally hearing the messagethat obesity is an issue of health and not of appearance. Treating thisepidemic requires a multidisciplinary approach and a commitment on thepart of legislators, health care executives, and medical professionals.
Prevention is critical, and all eﬀorts should be made to support increasingsafe physical activity for children and adolescents. Children and familiesalso should be educated about appropriate food choices and portion sizesin schools and by their physicians. Decisions about foods in the schoolsand at home should be driven by education and not by advertising or otheroutside forces.
The treatment of morbid obesity in adolescence ﬁrst and foremost should
be based on aggressive behavioral and dietary modiﬁcation. With onlya small daily increase in caloric expenditure and a relatively small decreasein caloric intake, many adolescents can achieve and maintain weight loss.
This goal requires constant encouragement and surveillance on the part ofa ‘‘coach,’’ whether that be family, a commercial weight loss program, ora physician. For adolescents with severe morbid obesity who have failedattempts at weight loss, the options are medical therapy or bariatric surgery.
Medical therapy is occasionally eﬀective in some patients and should beconsidered. Bariatric surgery is currently the most eﬀective method ofweight loss for morbid obesity. Current indications for bariatric surgeryin adolescence are more conservative than for adults, because the long-term consequences of this surgery in growing children are not known. Theunique psychological and physical issues of adolescence add another layerof complexity to the management of these patients. For that reason,morbidly obese teenagers are best treated in centers with special expertisein the care of adolescents. Because the long-term outcomes of bariatricsurgery in adolescents are not known, it is ethically and clinically importantthat these patients be enrolled, whenever possible, in long-term prospectiveoutcome studies.
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A common problem: Asthma is one of the most common lung problems in Australia, and affects as many as 1 in 5 children and 1 in 10 adults. Although it is common, asthma causes variable symptoms in different individuals. There is no cure for asthma. Asthma can, however, be controlled with long term treatment. First, a brief anatomy lesson: to understand lung disease it is important to rem
Code of Conduct Código de conducta Código de conducta I. Introducción La honestidad, integridad y el buen juicio de nuestros empleados, directivos y consejeros son fundamentales para la reputación y el éxito de Flint Group. Flint Group se esfuerza por ser un ciudadano corporativo confiable y por manejarse de modo que fomente relaciones más eficientes dentro de las com