Università degli Studi di Pisa
Scuola di Dottorato “G. Monasterio”
Programma: “Fisiopatologia medica e Farmacologia”
Application of new methods
of data mining and data analysis
in bariatric surgery
Tutor: Dottoranda: Dott.ssa Valeria Siciliano
Dott.ssa Monica Nannipieri Dott.ssa Sabrina Molinaro
Alle colleghe ed ai colleghi della Sezione di Epidemiologia e
Ricerca sui Servizi Sanitari IFC-‐CNR
Index
Introduction 1
Part 1. Hypoglycemia after bariatric surgery, epidemiology and mechanisms 3
1.1 Background 3
1.1.1 Bariatric surgery 4
1.1.2 Dumping syndrome and hypoglycemia 8 1.2 Clinical profile and episodes of dumping syndrome and hypoglycemia 10
1.2.1 Type of surgery 12
1.2.2 Weight loss 13
1.2.3 The hormonal profile 14
1.2.4 The glycemic profile 16
1.3 Dietary habits and episodes of hypoglycemia 17 1.3.1 Eating behavior after bariatric surgery 18
1.3.1.1 Food intolerance 19
1.3.1.2 Taste change 20
1.3.1.3 Decreased food reward 21
Part 2. Collecting data in clinical studies: the additional value using health
record system 22
2.1 Data mining: what data to collect 22 2.2 Data normalization and entity definition 25 2.2.1 Socio-demographic characteristics – ANAG 27 2.2.2 Hematochemical data – RICOVERI/AMBULATORI 28 2.2.3 Pharmacological treatments data– FARMACI 30
2.2.4 Surgery data - INTERVENTI 33
2.2.5 Dietary habits – DIETA 34
2.3 Data quality control 40
2.3.1 Missing data 41
2.3.2 Out of range 41
Part 3. Study of the pre-operative clinical characteristics in predicting
episodes of dumping syndrome and hypoglycemia 44
3.1 Objectives 44
3.2 Materials and methods 45
3.2.1 Study design 45 3.2.1.1 Exclusion criteria 45 3.2.1.2 Study duration 46 3.2.1.3 Ethics statement 46 3.2.2 Measures 47 3.2.3 Dataset 47 3.2.4 Statistical analysis 49 3.2.4.1 Outcome analysis 50 3.3 Results 50
3.3.1 Characteristics of the study population 50 3.3.2 Patients at risk for dumping syndrome and hypoglycemia after bariatric
surgery:comparing anthropometric measurements and laboratory
parameters 52
3.3.3 Patients at risk for hypoglycemia after bariatric surgery: comparing
OGTT pre-surgery 54
3.4 Discussion 54
Part 4. Study of the association of eating habits and episodes of
hypoglycemia 56
4.1 New statistical method for clinical epidemiology: Structural Equation
Modeling 58
4.1.1 Latent and Observed Variables 60 4.1.2 Dependent and Independent Variables 60
4.1.3 Graphical notation 60
4.2 Objectives 62
4.3 Materials and methods 62
4.3.1 Study design 62
4.3.3 Statistical analysis 66 4.3.3.1 Assessment of dietary patterns: Principal Component Analysis 66 4.3.3.2 Association analysis: Logistic regression model 67 4.3.3.3 Assessment of eating habits: Confirmatory Factor Analysis 67 4.3.3.4 Association between eating habits and hypoglycemia:
Structural Equation Models 68
4.4 Results 68
4.4.1 Description of the sample 68
4.4.2 Association between dietary patterns and hypoglycemia episodes using
a classical approach 69
4.4.2.1Assessment of dietary patterns using PCA 69
4.4.2.2 Breakfast patterns 70
4.4.2.3 Lunch patterns 70
4.4.2.4 Dinner patterns 71
4.4.2.5 Correlation between dietary patterns and grams intake per week 72 4.4.2.6 Association between dietary patterns and hypoglycemia episodes 73 4.4.3 Association between eating habits and hypoglycemia using a new
approach:Example 1 74
4.4.3.1 Assessment of eating habits using CFA 74 4.4.3.2 Association between eating habits and hypoglycemia using SEM 75 4.4.4 Association between eating habits, taste alteration, BMI reduction and
hypoglycemia using a new approach: Example 2 77 4.4.4.1 Assessment of eating habits using CFA 77 4.4.4.2 Association between eating habits, taste alteration, BMI reduction
and hypoglycemia using SEM 77
4.5 Discussion 79
Conclusion 81
1
Introduction
Althought the research in bariatric surgery has e increased xponentiallyover the past 10 years, there are many areas of this topic which are still unexplored or less known. Studies on long-term data including the interrelationships among dietary habits and hematological exams are lacking, as well as studies on the pre-operative clinical characteristics in predicting both short and long-term complications. Simply undergoing bariatric surgery will not cure obesity or control its associated comorbidities. Encouraging changes in diet and lifestyle is required, and lifelong follow-up for these patients is mandatory.
In order to monitor these changes as well as to fill the current knowledge gaps about bariatric surgery, it would be appropriate to implement a large integrated health record system. To integrate different data sources means collecting and linking data, for example from medical records or from interviews during outpatient visits. Data collection on bariatric patients requires a massive effort from clinical personnel responsible for the care of patients. However, the aim of a bariatric registry is not only related to the collection of data for research targets, but also to the monitoring of quality and safety outcomes in a view of benchmarking best practices in bariatric surgery. In this perspective, the first aim of this work is to implement a health record system, collecting data on patients undergoing bariatric surgery. Data collection on these patients may enable to evaluate outcomes, to facilitate studies on complications (e.g. dumping syndrome) as well as to improve patient management.
To date, it is well established that bariatric surgery is the most effective treatment for severe obesity; nevertheless, these procedures are not devoid of potential long-term complications, such as episodes of hypoglycemia. Postprandial hypoglycemia is increasingly recognized as a complication of bariatric surgery: its prevalence seems to be around 40% and the median time from surgery to symptoms is 2.7 years.
However, the fact that it is still unclear why some patients experienced hypoglycemia, while others were asymptomatic after surgery shows that the pathogenesis of hypoglycemia is poorly understood and is probably based on multifactorial causes.
2 The principal challenge for epidemiologists is to understand causal relationships between risk or protect factors and health outcomes, in most cases by analysing data from observational studies. Literature provides statistical models, not frequently used in epidemiology, that give the opportunity to delineate causes and effects from observational data, named Structural Equation Modeling (SEM).
The major advantage of SEM is its ability to estimate causal relationships among all parameters simultaneously (e.g. BMI reduction, taste change, hypoglycemia), taking into account direct and indirect effects of all variables. Particularly useful is also the possibility to estimate latent variables. Typically, there is no direct operational method for measuring a latent variable (i.e. eating habits), nevertheless, manifestations of a latent construct can be observed by recording or measuring specific features of the variables of studied subjects in a particular situation (i.e. foods eaten). The relationships among variables (observed and/or latent) are linear and, therefore easy to understand. The second aim of this work is to take advantage of these methods to analyse data from different sources in order to estimate direct and indirect effects on hypoglycemia episodes. Using this model, for example, we were able to find different effects of taste changes, mediated by eating habits.
Therefore, this study is intended to be innovative for both data mining (Bariatric Registry) and data analysis (Structural Equation Modeling).
3
Part 1. Hypoglycemia after bariatric surgery, epidemiology and
mechanisms
1.1 Background
Obesity is an increasingly serious health problem in nearly all Western countries. The estimated prevalence suggest that 7%-15% of subjects in developed countries are obese (Malik, 2013; James, 2008). In Italy, the prevalence of overweight subjects is about 35%, and most part are males, while the prevalence of obese subjects is about 10% (OECD, 2014). With developing countries registering rapidly rising obesity rates, over-nutrition overtook under-over-nutrition in terms of health impact, and no more is obesity a problem only of the Western world (Prentice, 2006; Ogden 2007; Finucane 2011). According to the data from the International Obesity Task Force, there are around 475 million obese adults with over twice that number overweight, that means around 1.5 billion adults are too fat. Over 200 million school-age children are overweight, making this generation the first predicted to have a shorter lifespan than their parents (IOTF, 2014). Obesity is today a pandemic.
Obesity is usually defined in terms of body mass index (BMI, kg/m2). The World Health Organization and the National Institutes of Health proposed guidelines for the classification of weight status based on the BMI (WHO, 2004). Accordingly, a BMI of 25.00-29.99 is considered overweight, a BMI of 30.00 to 34.99 is considered obesity class 1, 35.00-39.99 as class 2, and over 40 as class 3. Morbid obesity is usually defined as a BMI of over 40 or a BMI over 35 in combination with comorbidities. Obesity is an independent risk factor for a variety of chronic diseases such as diabetes, hypertension, coronary heart disease, knee osteoarthritis, and cancer (Preston, 2013). A study on the association between different grades of obesity and the number of life-years lost indicated that life expectancy can be up to 20 years shorter in severe obesity (Fontaine, 2003).
By the rise in obesity comes the demand for its treatment. However as with all diseases, there is a wide variation in patterns of obesity and the medical implications thereof in different ethnic groups and different environments. Current treatment modalities for
4 obesity include lifestyle modification, diet, and pharmacologic agents. However, their effectiveness and durability is limited. Surgery is the most effective treatment to date, resulting in sustainable and significant weight loss along with the resolution of metabolic comorbidities in up to 80% of cases (Buchwald, 2004; 2009). However, bariatric interventions also induce major changes in the anatomy and function of the gastrointestinal tract (Baptista, 2013). Nevertheless, these procedures are not devoid of potential long-term complications. Dumping syndrome may occur after procedures involving at least partial gastric resection or bypass, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (Tack, 2014). For example, postprandial, severe and recurrent hypoglycemia is a late complication of Roux-en-Y gastric bypass surgery (RYGB) and could contribute to the post-operative increase in mortality unrelated to disease (Neff, 2013).
1.1.1 Bariatric surgery
Bariatric surgery is the surgical treatment of severe or morbid obesity (DeMaria, 2007). In 1991, the National Institutes of Health established guidelines for the bariatric surgery (BMI ≥ 40 or BMI ≥ 35 in the presence of significant comorbidities). Using this surgery, weight loss is induced by 2 main mechanisms. The first mechanism is restriction of the stomach, effected either by placement of a band to narrow the gastric inlet (think of a choker necklace) or by removing part of the stomach to limit its capacity. The second mechanism is reduced nutrient absorption; a gastrointestinal bypass is created such that there is less surface area and contact time between food and intestine. The purely restrictive bariatric surgeries are called gastric banding or gastric stapling. The Biliopancreatic Diversion with or without duodenal switch (BPD) is mainly a malabsorptive bariatric surgery. Gastric bypass surgery is a combination of both restriction and malabsorption. The three most widely accepted procedures are: laparoscopic Adjustable Gastric Banding (AGB), laparoscopic Sleeve Gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) (Pasupathy, 2014). In gastric restrictive procedures, the digestive process remains intact and none of the GI tract is bypassed. After AGB or SL, a person can eat only about three-quarters to one cup of food. The
5 food must be well-chewed. Eating more than the stomach pouch can hold may result in nausea and vomiting. Restrictive procedures pose fewer risks than gastric bypass procedures, but they are also less successful because continuous overeating can stretch the pouch so that it accommodates more food.
The recognition was that obesity-related medical conditions improved significantly after bariatric surgery. In particular, type 2 diabetes mellitus (T2DM) appeared to be remitted after gastric bypass up to 80% of the time. Improvement was also noted in the control of blood pressure and cholesterol (Bunchwald, 2004). The largest meta-analysis addressing the risks of bariatric surgery to date including 161,756 patients reported perioperative morbidity of 10% to 17% and 30-day mortality rates of 0.08% to 0.35%. Re-operation rates ranged from 3% to 12%. The lowest numbers of early complications, but also highest re-operation rates, were noted after (Laparoscopic) AGB (Chang, 2013). Many physicians are concerned about referring patients for bariatric surgery because of the risks involved, but analysis of data from the prospective matched cohort Swedish obese subjects study points towards a long-term reduction in overall mortality with an adjusted hazard ratio of 0.71, associated with a significant reduction in cardiovascular and cancer related deaths in the surgical cohort compared to matched obese control subjects receiving usual care (Sjöström, 2004).
The multi-centre LABS-2 study group recently published detailed post-surgery weight loss outcomes up to 3 years, demonstrating a wide variation in individuals undergoing the same procedure. Although median weight loss at 3 years was 15.9% following LAGB and 31.5% after RYGB, closer examination of subjects’ individual data points demonstrated a marked heterogeneity. The majority of subjects in the LAGB group (62%) experienced initial rapid weight loss in the first 6 months, then a gradual weight loss until 2 years, after which the curve remains rather flat. This is in contrast to 76% of RYGB subjects who experienced rapid weight loss in the first year, gradual weight loss in the second year and then small weight regain between years 2 and 3 (Courcoulas, 2013).
Studies have also pointed out a loss at least 50% of excess weight to indicate successful surgical treatment (Mundi, 2013; Goldman, 2013). On other hand, failure of this
6 therapeutic approach represented by the incapacity of weight loss or weight regain has been estimated to occur in 20% of cases (Goldman, 2013). Weight regain after the minimum weight achieved has been observed 2 to 5 years after surgery (Magro, 2008). Some of the predictive factors of weight regain are the surgical technique used, the presence of eating compulsion and disorders (Ferraz, 2014; Robinson, 2014), the dilation of the gastric pouch, patient adhesion to follow-up and support group, and hormonal adaptations (Shah, 2006; Lopez, 2007; Mundi, 2013). However, other studies found that weight regain did not change the biochemical indicators (Ferreira Nicoletti, 2014).
Adjustable Gastric Banding (AGB)
AGB procedure involves attaching an inflatable band around the top portion of the stomach and tightening it like a belt to separate the stomach into a small pouch that serves as a new, much smaller, stomach and the rest of the stomach below the band. The band creates a narrow channel (or stoma) between these two parts of the stomach. This slows the movement of the food from the upper small pouch to the lower stomach. After the procedure, the diameter of the band around the stomach can be adjusted by a doctor by adding or removing saline. Like other restrictive procedures, Laparoscopic AGB may not achieve significant weight loss.
Sleeve Gastrectomy (SL)
SL uses staples to remove about 80% of the stomach. The remaining stomach, which is shaped like a "sleeve" will hold approximately one-quarter cup of liquid. Over time, the stomach can expand to hold one cup of food. This procedure was initially created as a first step of a two-step surgery (second step surgery involves changing the direction of food in the small intestine for a malabsorption, also called biliopancreatic diversion). Many patients lose the desired amount of weight and do not need this second surgery. Weight loss can be 33% to 60% of excess body weight at one year after surgery. Since the rest of the stomach has been removed, this procedure is not reversible.
7 Roux-en-Y gastric bypass (RYGB)
RYGB a surgical technique that combines the reduction of gastric capacity and intestinal malabsorption, is the surgical procedure most frequently used. The restrictive element can be achieved by stapling the stomach into two sections. The top section becomes a small pouch that serves as the "new" stomach. The small size of this newly formed stomach is so reduced that it "restricts" or limits the amount of food intake. It also provides a feeling of fullness and satisfaction with smaller portions of food. The lower section of the stomach no longer receives, stores, and mixes food but remains functional by continuing to secrete digestive juices. The malabsorptive element in gastric bypass is achieved by surgically dividing the small intestine in a certain area. Once divided, the lower part of the intestine (jejunum) is pulled up to directly connect to the small pouch. The other end of this divided intestine is surgically sewn back at a specific point further down the small intestine. The shape of the intestine now somewhat resembles a "Y". As a result, when food is eaten, it enters the new stomach, and then travels into the jejunum, first "bypassing" the upper part of the intestine. The effect of bypassing the upper portion of the intestine decreases the amount of calories and nutrients that are absorbed into the body. The RYGB may be performed with a laparoscope rather than through an open incision in some patients. People with a Body Mass Index (BMI) of 60 or more or those who have already had some type of abdominal surgery are usually not considered for this technique. RYGB permits the loss of 30% to 40% of the initial weight and of 60% to 75% of excess weight over a period of 1 year, the reduction and/or resolution of the major comorbidities related to excess weight, and an improved quality of life (Fried, 2013). In addition to the weight changes caused by surgical treatment, improved biochemical indicators have been reported to occur, with a reduction of serum triglycerides, low density lipoprotein (LDL), and fasting glycemia levels 6, 12 or 18 months after surgery, reaching normal values (Pinheiro, 2012). A greater excess weight loss was associated with a better lipid profile 4 years after surgery (Ferreira Nicoletti, 2014).
8 Biliopancreatic Diversion (BPD)
A BDP is primarily malabsorptive, and is a more complicated procedure than the Roux-en-Y gastric bypass. In this procedure a part of the lower stomach is removed. The part of stomach that is left is connected directly to the last part of the small intestine (jejunum). As food is digested, it completely bypasses a larger section of the small intestine than in the Roux-en-Y gastric bypass. This surgery may result in a greater degree of malabsorption than the Roux-en-Y, and consequently in greater nutritional deficiencies. It is not so commonly performed. A variation of the biliopancreatic diversion is a procedure called the duodenal switch (BPD-DS). This adaptation retains the part of the stomach that includes the valve that controls the release of food into the small intestine. This helps to prevent the "dumping syndrome" which can result in vomiting or diarrhea. A small part of the upper intestine (duodenum) is also retained.
1.1.2 Dumping Syndrome and Hypoglycemia
The most common reasons that bariatric surgery patients had to visit the emergency department within a three month period after surgery were: abdominal pain, emesis, dehydration and nausea. These complications could most likely be attributed to patient poor compliance with diet, resulting in the classical symptoms of the dumping syndrome which is common in patients that have undergone bariatric surgery (Gonzalez-Sánchez, 2007; Marks, 2010).
In some patients, a deregulation in carbohydrate metabolism between insulin secretion and sensitivity is observed, whereupon dumping syndrome happen. Dumping occurs in the postprandial period and is categorized into two forms, early and late, that differ in their pathophysiology. Their prevalence is not well studied, although it seems that 10% to 20% of patients are affected (Ukleja, 2005). Recent researcher studied a cohort of 70 patients who undergone gastric bypass surgery and found that 25.7% patients have a positive anamnesis for early dumping and 14.3% for late dumping, being it superior as what is described in the literature (Héraïef, 2014). However, the incidence of dumping following gastric bypass varies in the literature. It has been found to range between
9 15.7% and 76% (Sugerman, 1987; Mallory, 1996; Cawley, 2007). The etiology causing such inconsistency is yet lack.
Although there are no commonly accepted tests for dumping syndrome, radioisotope gastric emptying studies demonstrating rapid gastric emptying are often used to confirm the clinical suspicion. Several clinical scoring systems have also been used to support the diagnosis of dumping. Recently, investigators have suggested a simple provocative test to confirm the diagnosis of dumping. After ingestion of 50 g of oral glucose, a heart rate rise of greater than 10 beats per minute in the first hour has been found to be a sensitive predictor of early dumping. Late dumping is confirmed with this test by documenting typical vasomotor symptoms in the postchallenge period. Most patients present with early dumping, or a combination of both early and late dumping. Isolated late dumping, i.e. patients in whom hypoglycemia is the only symptoms, is very rare (Tack, 2014).
In patients with severe dumping, or in those whose symptoms fail to respond to dietary modification, the next step should be the use of octreotide, the long-acting somatostatin analogue. Octreotide acts to delay intestinal transit time, causes splanchnic vasoconstriction, and suppresses the release of a wide variety of enteral hormones, including insulin. For patients with debilitating dumping symptoms that are refractory to dietary modification and octreotide, remedial surgery should be considered. In general, a cautious approach when considering surgical therapy of dumping is appropriate, because most cases of dumping will improve with time and because no remedial operation has a 100% success rate (Sarosi, 2004).
Early dumping syndrome
Early dumping occurs within 30-60 minutes of eating and typically presents with both gastrointestinal and vasomotor symptoms. Gastrointestinal symptoms include fullness, bloating, crampy abdominal pain, nausea, vomiting, and explosive diarrhea. The vasomotor symptoms include diaphoresis, weakness, dizziness, flushing palpitations, and an intense urge to lie down. In early dumping, the rapid delivery of hyperosmolar chyme into the small intestine as a consequence of rapid gastric emptying results in
10 several maladaptive responses. The presence of hyperosmolar proximal small intestinal contents is thought to lead to fluid shifts into the intestinal lumen, which results in intestinal distension and precipitates the gastrointestinal symptoms of early dumping. In addition, an oral glucose challenge leads to both peripheral and splanchnic vasodilatation, with both peripheral and splanchnic blood pooling, which is thought to result in the vasomotor symptoms of early dumping. Release of a variety of gastrointestinal hormones is enhanced in patients with early dumping; these include enterglucogon, vasoactive intestinal peptide (VIP), peptide YY, pancreatic polypeptide, and neurotensin (Sarosi, 2004).
Late dumping syndrome
Late dumping occurs 2-3 hours after eating and usually presents with only vasomotor symptoms. In late dumping, the rapid delivery of glucose to the small bowel followed by rapid glucose absorption is thought to result in an exaggerated insulin release. This exaggerated insulin secretion combined with rapid gastric emptying results in a excess insulin state 2-3 hours after eating and hypoglycemia with subsequent vasomotor symptoms. The exact cause of the excess insulin is unclear, but the enteric hormone glucagon-like peptide-1 (GLP-1) may play an important role in late dumping (Sarosi, 2004). This syndrome is associated with postprandial hypoglycemia resulting from hypersecretion of insulin; this insulin hypersecretion is probably stimulated by the sudden increase in blood glucose due to the rapid emptying of the meal, containing sugars, in proximal gut (Holst, 1994).
1.2 Clinical profile and episodes of dumping syndrome and
hypoglycemia
Postprandial hypoglycemia is increasingly recognized as a complication of gastric bypass surgery. In recent study was found the median time from surgery to symptoms was 2.7 years (Marsk, 2010), which is consistent with the time lag of 1–5 years that has been reported in case studies (Goldfine, 2007).
11 The pathogenesis of hypoglycemia is poorly understood and is probably based on multifactorial causes. The modification of the gastric anatomy after bariatric surgery, such as sleeve gastrectomy or gastric bypass, are associated with the alteration of gastric innervations and both have a profound effect on gastric emptying (Ukleja, 2005). In fact, sleeve gastrectomy, resulting in abolition of the mechanisms of response to distension, such as adaptation and cyclic contractility of the stomach, causes an immediate emptying of gastric contents (Azpiroz, 1987). This accelerated emptying, in particular of liquids, is a primary determinant in the pathogenesis of dumping syndrome. Gastric emptying is controlled by several factors: fundic tone, duodenal and antropyloric feedback mechanisms, the enteric nervous system and circulating GI hormones. The bariatric surgery alters each of these mechanisms in different ways. It is observed that the oral administration of glucose in patients with dumping syndrome leads to vasomotor symptoms that induce an increase in heart rate, hematocrit, and a concomitant decrease in plasma volume (Duthie, 1959). The phenomenon of peripheral vasodilation in patients with dumping syndrome, in contrast with the reduction of blood volume, was observed for the first time by Hinshaw (Hinshaw, 1957). However, peripherical vasodilation has not been confirmed by other researchers (Vecht, 1996). In patients with dumping syndrome were observed higher postprandial levels of gut hormones such as GLP-1 pancreatic polypeptide, peptide YY (PYY), vasoactive intestinal polypeptide (VIP), neurotensin and GIP (Glucose-dependent insulinotropic peptide) (Lawaetz, 1983; Bloom, 1972) compared with asymptomatic subjects after bariatric surgery. It is hypothesized that these peptides participate in the pathogenesis of dumping syndrome by acting at various levels. Neurotensin, VIP, GIP, GLP-1 and PYY retard the motility of the upper gastrointestinal tract and reduce gastric and intestinal secretions. Then, the meal arrives quickly in the small intestine, the distal intestine (not proximal) recognizes a high concentration of undigested carbohydrates, followed by a rapid absorption of glucose in the bloodstream. Hyperglycemia stimulates the rapid and excessive secretion of insulin that can be followed by late reactive hypoglycemia. GIP and GLP-1 seem to be the main mediators of dumping syndrome (Naslund, 1999). In particular, the excessive release of GLP-1 induces hyperinsulinemic response and
12 subsequent late hypoglycemia (Holdsworth, 1969). As further confirmed, in obese patients treated surgically with gastric bypass Roux-en-Y were found secretion levels of GIP (sometimes), glucagon and GLP-1 higher than in non-surgical patients (Goldfine, 2007).
However, it is unclear why some patients develop symptoms of dumping syndrome, while others are asymptomatic after surgery. After gastric bypass, around 40% of patients have dumping syndrome symptoms (Banerjee, 2013; Papamargaritis, 2012). The syndrome seems to be procedure-specific and is probably not related to the weight loss per se because there was no significant difference in hypoglycemia postoperatively in patients that had undergone a restrictive procedure such as VBG or GB compared with the general population (Marsk, 2010).
1.2.1 Type of surgery
After bariatric surgery, dumping syndrome has mainly been reported in patients who underwent Roux-en-Y gastric bypass and other interventions involving partial gastrectomy. It has been speculated that dumping syndrome symptoms might be an essential component of the weight reduction after bariatric surgery, due to adverse effects on food tolerance and intake. However, a prospective series showed that weight loss after Roux-en-Y gastric bypass was not determined by the presence of dumping syndrome (Banerjee, 2013). So-called restrictive interventions like Sleeve gastrectomy would be expected not to predispose to dumping syndrome. However, in 2 prospective studies, it was reported that up to 40% of patients had symptoms suggestive of dumping syndrome 6 to 12 months after SG (Tzovaras 2012, Papamargaritis, 2012), and the same percentage, 42%, is observed in obese patients treated with RYGB, with remission between 18 and 24 months (Banerije, 2013). Other studies report episodes of reactive hypoglycemia are observed as late complication in 72% of operated patients with RYGB and in 3% of patients operated with Sleeve (Mingrone, 2012). The mechanisms underlying dumping syndrome after SL remain to be elucidated, but it is clear that this bariatric intervention also carries a risk of inducing both early and late dumping symptoms. A recent case report study, analyzing follow-up from patients following
13 LAGB, found few cases were identified to have symptomatic hypoglycemia, and recommend that hypoglycemia be investigated irrespective of bariatric surgery performed (Bairdain, 2013).
While post-bypass hypoglycemia is often responsive to dietary modification, a subset of individuals develops life-threatening neuroglycopenia, with loss of consciousness, seizures and motor vehicle accidents. Hypoglycemia may result in accidental deaths and as the rate of accidental deaths was higher in the GBP surgical group, and this may result in an underestimation of the number of patients with hypoglycemia (Marsk, 2010). Such patients require complex nutritional and medical management strategies to reduce postprandial insulin secretion in order to stabilize glucose excursions as well as frequent monitoring of glucose values. Although relative risk of hypoglycemia and related diagnoses were two to sevenfold higher in the post-gastric bypass population, absolute risk was small. While these data underscore that hypoglycemia is an important complication of gastric bypass, many questions regarding frequency, pathogenesis and optimal therapy remain unanswered (Patti, 2010).
1.2.2 Weight loss
In patients with severe dumping symptoms, weight loss and food fear may also be present. Studies found that in severe cases, dumping syndrome is associated with significant impairment of quality of life (Arts, 2009; Nguyen, 2013) and may contribute to significant weight loss by avoidance of food intake. Scavini et al. (2005) reviewed their cases of gastric bands and found a 3%-4% rate of asymptomatic hyperinsulinemic hypoglycemia; they attributed this to the reduction of body mass index (BMI) and the inherent improvement in insulin sensitivity. Nevertheless, in a recent study was found that dumping syndrome occurred in 22% of RYGB patients and was severe in 7.7% of cases; the presence of dumping syndrome was not related to the magnitude of weight loss, however, in patients with severe dumping syndrome, weight loss was greater and the quality of life tended to be lower than those with less severe dumping syndrome (Nguyen, 2013).
14 Contrary to popular assumption, Banerjee et al. (2013) observed a trend of a greater loss of BMI in the nondumpers compared to the dumpers. A couple of earlier studies had also contradicted this popular belief when they could not show any significant association between dumping and concomitant weight loss (Mallory, 1996; Loss, 2009). A subset of peripheral messengers, termed gut hormones, has been implicated in the mechanism of weight loss following bariatric surgery. Among them, ghrelin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK) have all been identified as potential players (Tadross, 2009).
1.2.3 The hormonal profile
Potential mechanisms of hypoglycemia include increased insulin secretion because of increased incretin hormones, increased islet functional activity, and increased insulin sensitivity (Patti, 2005). However the role of these hormones is controversies. The proposed mechanisms include also expansion of β-cell mass, enhanced β-cell function, and causes not related to the β-cell.
Two hormones, glucose-dependent insulinotropic peptide (GIP) and Glucagon-like peptide-1 (GLP-1) were believed to play a pivotal role in late dumping (Kreymann, 1987; Weir, 1995). GIP is produced in a duodenum and proximal jejunum, GLP-1 is secreted from the small bowel and colon. An increased secretion of GLP-1 has been observed after an oral glucose challenge in patients after gastric resection and esophagectomy (Miholic, 1993) and this exaggerated GLP-1 response may play an important role in hyperinsulinemia and reactive hypoglycemia in late dumping (Ukleya, 2005).
Although a recent paper provided evidence for a key role of glucagon-like-peptide-1 in the pathogenesis of late hypoglycemia after gastric bypass (Salehi, 2014), other factors have also been suggested to potentially play a role in mediating post-gastric bypass hypoglycemia, such as decreased levels of the appetite-stimulating and insulin counter-regulatory gastrointestinal hormone, ghrelin or alterations in other countercounter-regulatory hormones. Goldfine et al. (2007) measured ghrelin, as well as peptide YY, gastric
15 inhibitory peptide (GIP), glucagon, adiponectin, and leptin, but reported no differences in these hormones between gastric bypass patients with and without hypoglycemia. Few words should be spent on the role of these hormones in weight loss. In the last years, it became evident that the weight loss associated with RNYGB was multifactorial. Apart from the restriction of food intake due to a smaller gastric pouch and malabsorptive effects resulting from the distortion of the gastrointestinal anatomy, changes in the entero-endocrine axis have been increasingly held responsible for weight loss. Bypass patients have been found to elicit exaggerated PYY and GLP-1 responses to a small meal, which contribute to premature satiety and weight loss (Korner, 2005). It is likely that the exaggerated PYY and GLP-1 responses contribute to the premature satiety reported, and therefore weight loss (Tadross, 2009). In addition, the circulating ghrelin concentration is found inversely proportional to body mass index and is influenced by change in body weight (Purnell, 2007). However, the role of the serum ghrelin level in weight loss post RNYGB is widely debated. Multiple studies have shown reduction (Cummings, 2002; Morinigo, 2004), no change (Stoeckli, 2004), and an increase (Vendrell, 2004) in serum ghrelin following bypass.
Recent data from a cross-sectional study shows poor weight loss response after RYGB is associated with decreased suppression of the orexigenic hormone ghrelin and limited response of the anorexigenic hormone GLP-1 to meal challenge, but no difference in the anorexigenic hormone PYY response, underling the supportive role of ghrelin and GLP-1 in the success of the weight loss responde after RYGB; in contrast, gut hypertrophy does not appear to account for poor weight loss after RYGB (Hollanda, 2014). Despite these provocative associations between GLP-1 and post-bypass hypoglycemia, it has previously been difficult to determine whether elevated GLP-1 concentrations are simply associated with altered intestinal anatomy post-bypass, or actually contribute to the pathophysiology of hyperinsulinemic hypoglycemia (Patti, 2014). Otherwise, animal data has shown successful weight loss independent of ghrelin signaling after sleeve gastrectomy, a type of surgery associated with marked suppression of ghrelin (Chambers, 2013).
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1.2.4 The glycemic profile
Given the presence of altered anatomy following gastric bypass such that the proximal gut is excluded from continuity with nutrients, the possibility that some unknown factor produced by this tissue may contribute to glucose homeostasis has been raised (Thaler, 2009). For most patients with type 2 diabetes, such a factor could lead to the rapid and dramatic resolution of the disease, but in some cases it may cause hypoglycemia (Foster-Schubert, 2011). Goldfine (2007) and Marsk (2010) commented that there is no observable association between preoperative diagnosis of DM and the development of these symptoms. In fact, the overall proportion of persons with diabetes mellitus who undergo bariatric surgery and develop this complication is surprisingly low (Bairdain, 2013).
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1.3 Dietary habits and episodes of hypoglycemia
Clinically significant dumping can cause grave distress to the patient when sugar-dense foods are ingested and this gave rise to the belief that the presence of dumping would result in long-term changes in the dietary habits of the patients. It should compel the subject to show restraint toward consuming calorie-dense foods and should cause the patient to refrain from eating significant quantities as well (Benarjee, 2013). Dumping syndrome can occur when sugary foods are consumed. Sugars are rapidly ‘dumped’ into the small intestine where they exert an intense-osmotic effect, drawing fluid from the circulation into the intestine (Elliot, 2003).
The resolution of dumping symptoms is achieved in most cases by dietary modifications, in particular by the reduction of carbohydrate intake, and the adjustment of lifestyle. Daily food intake should be divided into at least 6 meals. Dietary prohibitions are very important. Fluid intake during meals should be restricted. Drinking liquids should be avoided for at least a half-hour after a meal. Complex carbohydrates (e.g. unsweetened cereals, pasta, potatoes, fresh fruit, and vegetables) are preferred. Simple sugars (e.g. candies, cookies, sodas, sports drinks, sweets) should be avoided. Milk and dairy products (e.g. milkshakes, sweetened yogurt, chocolate milk) are generally not well tolerated and should be also avoided. Protein (meat, fish, chicken, eggs) and fat intake should be increased to meet daily caloric needs because of restricted intake of carbohydrates. Many patients modify their diet according to a personal experience with food tolerance. Most individuals with relatively mild symptoms will respond to dietary changes. For patients with severe vasomotor symptoms (postprandial hypotension), lying down for 30 minutes postprandially may decrease the chance of syncope by delaying gastric emptying and improving venous return. Supplementation of dietary fibers (bran, methylcellulose) with meals has been proven effective in the treatment of hypoglycemic episodes (Ukleja, 2005). Foods that are identified as causing dumping syndrome include ice cream and pastries (Fujioka, 2005). A recent qualitative analysis of post bariatric surgery patients suggested that dumping syndrome was the main deterrent to eating high-sugar foods or to eating too
18 quickly. While most participants never consumed a particular food again, a few stated it took more than one experience of dumping syndrome to avoid that food (Lynch, 2014).
1.3.1 Eating behaviours after bariatric surgery
Data on food choice and other eating behaviors have important implications for understanding the mechanisms of bariatric surgery. These data strongly questioning about the hypothesis that gastric volume reduction is the primary driver of weight loss (i.e. after RYGB or VSG), and in particular the hypothesis that reduced stomach size caused weight loss only due to a physical limitation on food intake. Fat malabsorption, dumping syndrome, food tolerance and changes in taste preference for specific foods have all been suggested as reasons for the higher weight loss observed after gastric bypass in comparison with stapled gastroplasty: it may due to substantial differences in post-operation food preference between surgeries (Kenler, 1990). In addition, animal experimenters showed that VSG and RYGB both cause decreased fat intake (Hajnal, 2010; Shin, 2011; Chambers, 2012), and when VSG and RYGB were compared directly, both procedures caused comparable changes in food choice (Wilson-Pérez, 2013).
The real matter is to understand in which way these foods choices contribute to the favorable outcomes for these bariatric procedures (i.e. weight loss) and complications, such as hypoglycemia. Therefore it seems that food choice is a side effect of RYGB and VSG surgeries rather than a primary impetus for weight loss. These findings open up a question on another issue regarding the minority of patients who do not lose substantial amounts of weight: it may due to the noncompliance with directions from their surgeon about foods to be avoided. Animal experiments suggested that in rats (that did not receive any instructions to follow after the surgery), even in the absence of nutritional counseling, the surgeries result in dramatic weight loss (Wilson-Pérez, 2013). It seems to suggest that the failure to comply with nutritional guidelines is unlikely to be the primary reason that patients fail to lose weight. In fact, the majority of patients seeking bariatric surgery have previously received numerous indications to change what they eat, and there is no reason to believe that such indications are more convincingly after
19 surgery. It seems that patients succeed in following such advice after surgery as the direct result of the biological impact of the surgery on systems that control food behaviors (Stefater, 2012).
Examining food choice, foods are often grouped into categories (meats, grains, fruits, vegetables, fish, etc.) or analyzed by their macronutrient content. Although there is large literature describing altered food choice or food preferences after bariatric surgery, the methodology and categorization of foods varies widely across these studies. These works examined eating behavior after bariatric surgery, RYGB surgery specifically, quantifying postoperative food choices, and comparing those with pre-surgical food choices (or with a control group), or comparing postoperative food choices between different kinds of bariatric surgery. For example, studies that focus on macronutrient content have indicated that RYGB patients decrease their relative intake of fat and correspondingly increase intake of carbohydrate (le Roux, 2011). Studies that grouped foods according to other categories have variously reported, among patients after RYGB, decreased intake of meat (Halmi, 1981), sweets, soda, milk and ice cream (Kenler, 1990; Olbers, 2006), and increased intake of fruits and vegetables (Olbers, 2006; le Roux, 2011), as well as poultry, fish, and eggs (Ernst, 2009).
1.3.1.1 Food intolerance
One explanation for changed food choices after bariatric surgery is the presence of aversive symptoms after the consumption of certain kinds of foods, which drives patients to avoid those foods (Stefater, 2012). In general, these aversive symptoms are referred to food intolerance but may include several different kinds of postprandial distress, including dumping syndrome and vomiting. However, food choice does not seem to be a consequence of food intolerance. Sweet intolerance after RYGB was attributed to symptoms of the dumping syndrome (Halmi, 1981) and many RYGB patients also reported dizzy and nauseated after ingesting sweet-tasting solids (Kenler, 1990), but these symptoms tend to improve over time. Food intolerance is even less common with VSG, but the effects on food choice are similar to RYGB (Schweiger, 2010). In particular, food tolerance is better in RYGB than AGB in the long term:
20 RYGB patients experience the poorest food tolerance in the immediate postoperative period, but it gradually improves over time, whereas AGB patients show a deteriorating gradually food tolerance (Suter, 2007). Considering food categories, AGB patients had the poorest food tolerance, the highest frequency of vomiting, and the lowest satisfaction with their eating behaviour compared with other surgeries. AGB patients had the poorest tolerance for red meat, bread, and pasta, instead, VSG had the highest tolerance for red meat compared with the other surgeries (Schweiger, 2010).
1.3.1.2 Taste change
Another explanation for changing food preference is the altered taste for some foods (Stefater, 2012). It has been known for some time that individuals who have undergone RYGB have profoundly altered taste perception, i.e. sweet-tasting food (Burge, 1995; Scruggs 1994). In a retrospective cross-sectional study of RYGB patients by Tichansky et al. (2006), 82% of patients reported a change in the taste of food or beverage, of which 92% described it as a decrease in the intensity of taste. The same study found contradictory results comparing RYGB and AGB. This comparison indicated that 65% of RYGB patients reported a decrease in the taste of sweet foods, whereas 62% of AGB patients reported an increase in the same (Tichansky, 2006). Changes in taste after RYGB are not explained by common mediators of taste, such as zinc deficiency, liver and kidney impairment, increasing age or glycogenic status (Scruggs, 1994). Studies have also shown that following RYGB, a significant up-regulation in taste acuity for bitter and sour was observed along with a trend toward a reduction in salt and sweet detection and recognition thresholds (Scruggs, 1994).
Given that, taste plays a large role in food selection, therefore these findings implicate some involvement of the gustatory system. Gastric bypass has been shown to increase postprandial levels of gut hormones including peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) (Bueter, 2010; Goldfine, 2007). Peripheral PYY and GLP-1 administration in mice activates neurons in brainstem areas that have been suggested to mediate effects of distinctive classes of aversive stimuli (Halatchev, 2005) and have been shown to be effective at conditioning taste aversions (Thiele, 1997). Thus,
21 exaggerated postprandial GLP-1 responses after gastric bypass cannot be excluded as a potential mediator of a food preference after gastric bypass in rats. In addition, GLP-1 or PYY may also influence fatty perception, and there may be parallels with the recognition of sweet stimuli. Mice lacking the GLP-1 receptor show decreased behavioral responsiveness to sucrose (Thiele, 1997). The importance of changes in taste is unknown, but further research is required to clarify their role. They may play a substantial role as, when asked, 83% of patients agreed that alterations in taste led to better weight loss (Tichansky, 2006).
1.3.1.3 Decreased food reward
On the other hand, bariatric patients may decrease intake of certain foods due to decreased food reward: after surgery, these patients may like some foods less. Although this may be a general decrease in food reward related to all caloric sources, it may also vary according to kind of food (Stefater, 2012). These changes may be learned based on experiences with food intolerances or taste changes. Changes in behavior and perception, such as changed food choice, changed taste, and food reward, must ultimately stem from changes in the brain. When examined by functional magnetic resonance imaging, RYGB patients exhibited a selective reduction in neuronal responses to high-calorie foods (Ochner, 2011). Dopamine, a neurotransmitter associated with various kinds of rewarding stimuli including food, has also been reported to change after RYGB (Steele, 2010).
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Part 2. Collecting data in bariatric surgery: the additional value using
health record system
To fill the current gaps in the knowledge about bariatric surgery, a registry of patients having weight loss surgery from 2006 to the present time in a large integrated health record system has been created. This registry was also designed to monitor quality and safety outcomes and assist the clinical personnel responsible for the care of these patients (using graph and statistical indices). As reported in recent study (Coleman, 2014), using a bariatric registry may enable to allow us to facilitate future studies and ensure that new findings are translated into clinical practice in a timely fashion.
2.1 Data mining: what data to collect
Several well-described nutritional problems such as B12 and iron deficiency will be noted in patients after bariatric surgery. These and other mineral and vitamin problems will need to be screened and treated. If these problems are left undiagnosed, severe and irreparable problems can result. Early problems, such as vomiting and dumping syndrome, will be easily recognized and treated, but other long-term problems, such as changes in bone metabolism, will need to be monitored. Again, if some of these long-term problems are not addressed in a timely fashion, then eventual treatment becomes much more difficult. It is established the need to recognize the common as well newer problems that are now developing in the patient who has had bariatric surgery. Patients who have undergone bariatric surgery require medical follow-up for reasons that are often determined by the type of surgical procedure performed (Fujioka, 2005). There are many follow-up actions recommended after bariatric surgery.
Adjustable Gastric Banding:
- from the first postoperative month, the follow-up should be performed every 3 months until we obtain a satisfactory weight loss (if necessary, with repeated narrowing of the band). Subsequently, these checks should be made at intervals not exceeding one year;
23 - adjustments of the bandage should be made in consideration of the weight loss at each follow-up and the type of device used, taking into account an interdisciplinary decision and a consulting by a medical staff (surgeon and radiologist) with adequate experience. A data collection of all adjustments will be required.
Gastric Bypass:
- clinical and instrumental follow-up in the first postoperative month, every 3 months for the first year, every 6 months for the second year and then annually;
- nutritional status and metabolic should be checked periodically to prevent vitamin deficiencies in micronutrients and to ensure adequate supplementation. During the tests, drug treatments previously needed should be reassessed for its correction or elimination. Biliopancreatic Diversion:
- clinical and instrumental follow-up in the first postoperative month, every 3 months for the first year, every 6 months for the second year and then annually;
- oral supplementation of vitamins (water soluble) and micronutrients should be prescribed routinely and for life to compensate for the possible reduced intake and absorption. It is also prescribed calcium supplementation. It is, finally, strongly recommended a protein intake of at least 90 g / day.
Sleeve gastrectomy:
- clinical and instrumental follow-up in the first postoperative month, every 3 months for the first year, every 6 months for the second year and then annually;
- nutritional status and metabolic should be checked periodically to prevent vitamin deficiencies in micronutrients and to ensure adequate supplementation. During the tests should be reassessed even comorbidities may be present for its correction or elimination of drug treatments previously needed;
- oral supplementation of vitamins and micronutrients should be prescribed routinely to compensate for the possible reduced intake and absorption.
Laboratory tests to evaluate the metabolic and nutritional status should be made quarterly in the first year and then at least annually, except as otherwise indicated (dosage: glucose, albumin, hemoglobin, iron, ferritin, vitamin B12, vitamin D3,
24 parathyroid hormone, calcium, magnesium, zinc and copper; tests of liver and kidney function). Based on the results of these tests may be necessary to correct the deficiencies with parenteral treatment of vitamins and micronutrients. Regarding the follow-up of nutritional and metabolic problems after bariatric surgery, Fujioka suggested that the follow-up of the morbidly obese patient can conveniently be divided into two areas: the issues of surgical complications and weight loss during the first year, and the nutritional and metabolic issues that arise after the first year (Fujioka, 2005).
Common issues during post-operative first year:
- Vomiting and dumping syndrome: it typically happens one to three times a week and is usually due to overeating or not chewing food adequately. If vomiting becomes more frequent, low potassium and/or low magnesium levels often occur, requiring oral replacement.
- Hair loss: it is frequently observed 3–6 months after surgery. Patients note diffuse shedding of normal hair; lasting as long as 6–12 months, it can be terribly distressing to the patient.
Common issues after post-operative first year:
- B12 deficiency: as weight loss begins to slow down, the risk of other nutritional problems increases. B12 is one of two most common problems and often do not respond to typical multivitamin supplementation (Provenzale, 1992). Such nutrient issues are primarily seen with gastric bypass and any of the malabsorption procedures.
- Iron deficiency: after gastric bypass is usually only found in menstruating women. Ferritin or iron levels and erythrocyte counts need to be monitored, as iron deficiency can develop early after surgery or years later; one study found that iron stores continuously declined up to 7 years after bypass surgery (Avinoah, 1992).
Long-term metabolic issues after bariatric surgery:
Several articles focused on the problems with bone mineralization in gastric bypass patients (Coates, 2004; von Mach, 2004). Long-term follow-up of this growing and aging population will need to monitor bone health and metabolism. Currently following vitamin D, calcium, and parathyroid hormone levels, as well as bone densitometry is
25 required. One form of bone demineralization, secondary hyperparathyroidism, has been reported by several groups to occur in patients who have had gastric bypass (Goode, 2004; Fujioka, 2004). While the prevalence is unclear, it appears to be more common than previously thought. Protein deficiency is easy to recognize by following albumin. Fat malabsorption manifests its presence by loss of soluble vitamins. In general, fat-soluble vitamins A, D, and K will be deficient in two-thirds of these patients within 4 years after surgery. Up to 50% will have hypocalcemia, and all of these patients with low vitamin D levels will have secondary hyperparathyroidism (Slater, 2004; Newbury, 2003).
Compliance with long-term follow-up is vital, as nutritional and metabolic problems can be easily treated or avoided. With increasing numbers of patients undergoing bariatric surgery, collecting data using health record system will need to become routinely in the follow-up of such patients.
2.2 Data normalization and entity definition
The first step of the normalization involved the data collection, relating to bariatric patients (inpatient and outpatient medical records, prescriptions for medications, interventions, etc.) in order to proceed with the standardization of data from different sources.The socio-demographic characteristics of the patients are collected into the main entity (ANAG), into which all attributes are reported “in clear” (First Name, Last Name, Gender, Date of birth, Address, etc.). At the same time a Unique Patient Code (UPC), which is a numeric identifier, has been generated so that all the related entities concerning the patient were subsequently created and fed with all information (MEDICATIONS, SURGERY, CLINICAL RECORD, ADMISSIONS, DIET, etc.). The ‘de-identification’ system for each patient is performed using the health records from several sources, with the aim of separating the patient’s personal and sensitive information into a single entity (ANAG), and collecting all the available information for each patient over time, referring to UPC, which is the only attribute available in the linked tables: pre-intervention hospitalization data, surgery data, subsequent outpatient visits, diet and medications (Figure 2.1).
26 Figure 2.1. Main Entities and their relationships
ANAG INTERVENTI FARMACI AMBULATORI RICOVERI DIETA 1 N 1 N 1 N 1 1 1 N
The relationships shown in Figure 2.1 (1 -> N or 1 -> 1) express the degree of association between records belonging to different entities. For example, for a single patient registered in ANAG may be present 1 up to N records in AMBULATORI exams and further prescribed into FARMACI (from 1 to N drug prescriptions). The link to the entity of RICOVERI is 1 -> 1, if we considered for each patient the first bariatric surgery. The schema entities have been implemented in a dedicated web system, used during outpatient activities by physicians, to register patient data; a menu picture of the software application is shown in Figure 2.2.
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2.2.1 Socio-demographic characteristics – ANAG
The socio-demographical data are collected through the patient's folder admission. The entity ANAG has been standardized according to the path described in Table 2.1. The unique code assigned to each patient UPC, is expressed by the field T_ANAG_CHIAVE. Fields with prefix D_ are linked to predefined dictionaries (provinces, municipalities, etc.). Being a numeric identifier, T_ANAG_CHIAVE (UPC field) represents the ‘anonymous’ link with the other archives regarding the patient, and it is configured in all entities; this process will allow to always refer to a ‘de-identified’ patient. Personal data are stored into a single entity (ANAG) and won’t be directly accessible.
Table 2.1 Standard Fields for ANAG
The corresponding functionality of the web platform, for data management of socio-demographic characteristics of the patient is shown in Figure 2.3.
28 Figure 2.3 Chibar Web system – Screen of Patient socio-demographic characteristics
2.2.2 Hematochemical data – RICOVERI/AMBULATORI
Blood and biochemical exams for each bariatric patient are collected on different paper templates. After a standardization process, carried out with bariatric physicians, we have identified the exams of interest (about 150 examinations) encoded in the entity D_PVEMAT; a further step of standardization has consisted in setting values of normality (T_PVEMAT_UMINNORM, T_PVEMAT_UMAXNORM) in order to be able to detect, even in the interface, the presence of values out of range (Table 2.2).
29 The field T_PVEMAT_TIPOREGIME is used to discern the exams related to hospitalization (RICOVERI) from outpatient examinations (AMBULATORI), and the same exams have been recorded in both types of record.
The value 'R' indicates 'Admission Exams', the value 'A' indicates 'Outpatient Exams'. In the first case the field ‘hour’ is meaningful (T_PVEMAT_ORAEXMEMAT) because, during a hospitalization, the patient may repeat the same exam during the same day, at different hours.
Note the field T_ANAG_CHIAVE in the RICOVERI/AMBULATORI entity, with the aim to link each record with the corresponding patient, through its unique code (UPC information).
Table 2.2 Standard fields for RICOVERI/AMBULATORI entity
An overview of haematochemical data collected for RICOVERI/AMBULATORI, are shown in Figure 2.4. Values out of normal range are highlighted with red color in the screen. For some specific exams, which could be provided by different laboratories, two more fields are available in the screen to set a specific range of normality values (MIN value, MAX value) for instance HbA1c, Azotemia / Urea, Creatininemia, etc.
30 Figure 2.4 Chibar Web system – Screen of Hematochemical data – RICOVERI/AMBULATORI
2.2.3 Pharmacological treatments data– FARMACI
Drug therapies have been standardized using the ATC "Anatomical Therapeutic Chemical Classification System" codes, an alpha-numeric system of classification Anatomical Therapeutic and Chemical that categorizes drugs based on a scheme that implicates 5 levels of hierarchy.
31 For example, the coding of Diazepam and Lorazepam are reported below:
The Diazepam is identified by the code: N05BA01; the Lorazepam by the code: N05BA06
N → Nervous System - Anatomical Group N05 → Psycholeptics - Therapeutic Group
N05B → Anxiolytics - Therapeutic Pharmacology Subgroup
N05BA → Benzodiazepine - Therapeutic Chemical-Pharmacological Subgroup N05BA01 → Diazepam - Chemical Subgroup
N05BA06 → Lorazepam - Chemical Subgroup.
Once chosen the ATC code as the encoding standard for the drugs, it is stored in the field D_DRUG_CODE in the FARMACI entity (Table 2.7).
Table 2.3 Standard fields for FARMACI entity
Note the field T_ANAG_CHIAVE in the FARMACI entity, with the aim to link each record with the patient, through its unique code.
For each drug therapy, ‘start date’ and ‘end date’ of therapy are recorded in T_DRUGTREAT_START and T_DRUGTREAT_END. D_DRUGWAY_CODE is a link to the dictionary of way of administration, which are also standardized according to the values of Table 2.4.
32 Table 2.4. Standard way of administration of pharmaceutical drugs.
In Chibar Web system a dedicated interface has been developed to fill out pharmacological prescriptions, as shown in Figure 2.5, with all attributes described: ‘Start date’, ‘End date’ of therapy, ‘Dosage’, ‘Way of administration’, etc.
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2.2.4 Surgery data - INTERVENTI
Surgery data for each patient are collected into the INTERVENTI entity (Table 2.5).
Table 2.5. Standard fields for the INTERVENTI entity
The standard information about the surgery is: the date of the surgery, weight prior to surgery, and type of surgery. The type of surgery, D_TIPINT_CHIAVE, links with the dictionary of possible bariatric surgery, shown in Table 2.6.
Table 2.6 Type of surgery
Note the field T_ANAG_CHIAVE in the INTERVENTI entity, with the aim to link each record with the patient, through its unique code (Table 2.1).
The corresponding web screen for the surgery data management is shown below. Specifically, for code intervention BEN (Gastric Banding) it is possible to specify a value of insufflation/desufflation, as shown in Figure 2.6.
34 Figure 2.6 Chibar Web system – Screen of Surgery data
2.2.5 Dietary habits - DIETA
Patients undergoing to bariatric surgery, are interviewed in relation to: dietary changes, any changes in taste and disorders (nausea, vomiting). These questionnaires are administered periodically by the medical specialist, during outpatient visits, to monitor changes in lifestyle and in particular into the diet. The DIETA entity is shown in Table 2.7.
35 Table 2.7 Standard fields for DIETA entity
The structure of this entity reflects the coding (non-speaking) of the fields assigned by the tool used for the implementation (open source tool, Limesurvey).
A specific part of the Chibar Web platform is dedicated to register detailed data of patient diet. Several web screens have been developed, and two examples are depicted below (Figure 2.7, Figure 2.8).
36 Figure 2.7 Chibar Web system – Dietary habits
37 A small part of the web interfaces designed to fill out data of dietary habits, is shown in Figure 2.7. Detailed information collected about the breakfast composition is reported in Figure 2.8.
The information stored in the questionnaire DIET concerns: the composition of meals during a standard week (Breakfast, First Snack, Lunch, Second Snack, Dinner), in order to calculate an average estimate of the grams and calories consumed by each patient during a single day (Table 2.8). They were also asked about drinks which may have been drunk between meals (with gas and/or sweetened), alteration of taste (from sweet to salty or vice versa), presence of vomiting, hair loss, etc.
Table 2.8. Dietary Habits from “Questionario alimentare pre-post intervento”:https://epid-prod.ifc.cnr.it/chibar/
Variables name Description
A1 Visit A2 Num. questionnire A3a Surname A3b Name A4 Gender A5 Birth date A6 Interview date
B1 Presence of vomiting after surgery / after the last control?
B1a1 Because ingestion of food is too fast B1a2 Because excessive amount of food ingested B1a3 If you have had vomiting, specify the cause B1a4 APPETITE: Compared to before surgery
B1a5 APPETITE: Compared to the previous control (if there was)
B3a Taste change
B3a1 Salty foods. If yes, describe the perceived change in taste B3a2 Sweet foods. If yes, describe the perceived change in taste B3a3 Greasy / fried foods. If yes, describe the perceived change in taste B3a4 Other. If yes, describe the perceived change in taste
B3a5 If other, specify
B3a6 Consumption of SWEET foods
C1 Breakfast
C1a1 Cereals (bread, crackers, breadsticks) C1a2 Biscuits (low fat intake)
C1a3 Biscuits (medium fat intake) C1a4 Biscuits (high fat intake) C1a5 Brioche
C1a6 Homemade cake C1a7 Cold cuts C1a8 Cheese
C1a9 Eggs
C1a10 Pizza
C1a11 Milk
C1a12 Yogurt C1a13 Fresh fruits C1a14 Fresh fruit juice C1a15 Fruit juice C1a16 The / Herb tea C1a17 Coffee C1a18 Marmalade
