Gastric Bypass For Severe Obesity Research Articles

Neuropathy 10–15 years after Roux-en-Y gastric bypass for severe obesity: A community-controlled nerve conduction study

ObjectiveWe searched for long-term peripheral nerve complications 10–15 years after Roux-en-Y gastric bypass surgery (RYGB), using a comprehensive nerve conduction study (NCS) protocol. MethodsPatients (n = 175, mean age 52.0, BMI 35.2) and 86 community-controls (mean age 56.8, BMI 27.2) had NCS of one upper and lower limb. New abnormality scores from 27 polyneuropathy-relevant (PNP27s) and four carpal tunnel syndrome-relevant NCS-measures (CTS4s) were compared between groups with non-parametric statistics. Estimated prevalences were compared by 95 % confidence limits. The clinical neurophysiologist’s diagnosis was retrieved from hospital records (PNP-ncs, CTS-ncs, other). ResultsAbnormality score did not differ between RYGB and control groups (PNP27s: 1.9 vs 1.7, CTS4s: 0.7 vs 0.6, p > 0.29). BMI correlated weakly with CTS4s in patients (rho = 0.19, p = 0.01), and less with PNP27s (rho = 0.12, p = 0.12). Polyneuropathy (PNP-ncs) prevalence was 12 % in patients and 8 % in controls. CTS-ncs prevalence was 21 % in patients and 10 % in controls (p = 0.04). ConclusionsNCS-based abnormality scores did not differ between patients 10–15 years after RYGB and community-recruited controls, neither for PNP nor CTS. SignificanceLong-term polyneuropathic complications from RYGB have probably been avoided by modern treatment guidelines. NCS-diagnosed CTS is common in overweight RYGB patients. RYGB-patients with significant neuropathic symptoms need clinical evaluation.

Iron Deficiency and Anemia 10 Years After Roux-en-Y Gastric Bypass for Severe Obesity.

Iron deficiency with or without anemia is a well-known long-term complication after Roux-en-Y, gastric bypass (RYGB) as the procedure alters the gastrointestinal absorption of iron. Iron is essential for hemoglobin synthesis and a number of cellular processes in muscles, neurons, and other organs. Ferritin is the best marker of iron status, and in a patient without inflammation, iron deficiency occurs when ferritin levels are below 15 µg/L, while iron insufficiency occurs when ferritin levels are below 50 µg/L. Lifelong regular blood tests are recommended after RYGB, but the clinical relevance of iron deficiency and iron insufficiency might be misjudged as long as the hemoglobin levels are normal. The aim of this study was to explore the frequency of iron deficiency and iron deficiency anemia one decade or more after RYGB, the use of per oral iron supplements, and the frequency of intravenous iron treatment. Nine hundred and thirty patients who underwent RYGB for severe obesity at three public hospitals in Norway in the period 2003–2009 were invited to a follow-up visit 10–15 years later. Results from blood tests and survey data on the use of oral iron supplements and intravenous iron treatment were analyzed. Ferritin and hemoglobin levels more than 10 years after RYGB were available on 530 patients [423 (79.8%) women]. Median (IQR) ferritin was 33 (16–63) µg/L, and mean (SD) hemoglobin was 13.4 (1.3) g/dl. Iron deficiency (ferritin ≤ 15 µg/L) was seen in 125 (23.6%) patients; in addition, iron insufficiency (ferritin 16–50 µg/L) occurred in 233 (44%) patients. Mean (SD) hemoglobin levels were 12.5 (1.4) g/dl in patients with iron deficiency, 13.5 (1.2) g/dl in patients with iron insufficiency, 13.8 (1.3) g/dl in the 111 (21%) patients with ferritin 51–100 µg/L, and 13.8 (1.2) g/dl in the 55 (10%) patients with ferritin >100 µg/L. Two hundred and seventy-five (56%) patients reported taking oral iron supplements, and 138 (27.5%) had received intravenous iron treatment after the RYGB procedure. Iron deficiency or iron insufficiency occurred in two-thirds of the patients 10 years after RYGB, although more than half of them reported taking oral iron supplements.

Gastrointestinal quality of life before and short- and long-term after Roux-en-Y gastric bypass for severe obesity.

Overall quality of life (QoL) is generally improved after bariatric surgery. Gastrointestinal (GI) symptoms including abdominal pain have been reported in up to >30% of patients after Roux-en-Y gastric bypass (RYGB), and may negatively influence QoL, especially GI-QoL. To evaluate the evolution of GI symptoms and GI-QoL short- and long-term after RYGB. Two public hospitals METHODS: Candidates for bariatric surgery (n = 128, BMI = 44.2 ± 7.4) or patients who had undergone RYGB 2-4 years (n = 161, BMI = 29.3 ± 15.9) and 5-10 years (n = 121, BMI = 31.3 ± 6.5) before were invited to complete a questionnaire combining 3 validated questionnaires (GIQLI, GSRS, and PCS) specifically designed to evaluate GI-QoL. Scores were compared between the preoperative, early, and late postoperative periods. The GIQLI score improved from 88.1 before surgery to 118.6 (P < .0001) and 109.7 (P < .0001) in the early and late postoperative periods respectively. GSRS score improved from 15.6 to 10.1 (P = .0001) and 12.8 (P = .012), and PCS-score improved from 19 to 4.5 (P = .0001) and 8.3 (P= .0001), respectively. The GI subscore of the GIQLI improved from 57.4 to 62.1 (P = .007) in the early period but was not significantly different in the late period (59.3 versus 57.4, P = .3). The psychological impact of GI symptoms decreased at both postoperative time points. GI-QoL is markedly improved after RYGB, and this improvement persists up to 10 years. GI symptoms decrease early after surgery and do not worsen in the longer term. Their psychological impact is markedly reduced.

Assessment of self-rated health 5 years after Roux-en-Y gastric bypass for severe obesity.

BackgroundPatients' perceptions of health change after bariatric surgery are complex. The aim of this study was to explore whether self‐rated health (SRH), a widely used tool in public health research, might be relevant as an outcome measure after Roux‐en‐Y gastric bypass (RYGB) for severe obesity.MethodsThis was a single‐centre retrospective study of a local quality registry. SRH score was registered at baseline and 5 years after RYGB. SRH, one of the 36 items in the quality‐of‐life Short Form 36 (SF‐36®) questionnaire, is the answer to this single question: ‘In general, would you say your health is excellent (1), very good (2), good (3), fair (4) or poor (5)?’ Change in SRH was analysed in relation to change in weight, co‐morbidities and quality of life after 5 years.ResultsOf a total of 359 patients who underwent RYGB between September 2006 and February 2011, 233 (64·9 per cent) reported on SRH before and 5 years after surgery. Of these, 180 (77·3 per cent) were women, and the mean(s.d.) age was 40(9) years. Some 154 patients (66·1 per cent) reported an improvement in SRH, 60 (25·8 per cent) had no change, and SRH decreased in 19 patients (8·2 per cent). SRH in improvers was related to better scores in all SF‐36® domains, whereas SRH in non‐improvers was related to unchanged or worsened scores in all SF‐36® domains except physical function.ConclusionTwo‐thirds of patients reported improved SRH 5 years after RYGB for severe obesity. In view of its simplicity, SRH may be an easy‐to‐use outcome measure in bariatric surgery.

Comparing the Outcomes of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass for Severe Obesity

Comparing the Outcomes of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass for Severe Obesity

Barrett's esophagus before and after Roux-en-Y gastric bypass for severe obesity.

Barrett's esophagus (BE) has been associated with obesity and metabolic syndrome. Laparoscopic Roux-en-Y gastric bypass (LRYGB) may represent a surgical approach which addresses both severe obesity and BE. LRYGB diverts bile away from the gastric pouch and esophagus due to the long Roux limb, and very little acid is produced in the cardia-based gastric pouch. Furthermore, surgically induced weight loss may diminish systemic inflammation, which may contribute to metaplastic changes in the esophagus. Moreover, improved compliance with proton-pump inhibitor therapy, as a consequence of enrolling in a bariatric program, will decrease acid production further. Decreased duodeno-gastro-esophageal reflux should lead to decreased BE. In this study we examine the effect of LRYGB on regression of BE. We performed a review of all patients with biopsy proven BE, who underwent LRYGB at our institution. A total of 19 patients were identified. A subset of those patients was identified who had at least 1year of clinical, endoscopic, or histological data, comprising a total of 14 patients. Seven of these patients had symptoms of gastroesophageal reflux. All 19 patients had short-segment BE. One patient had low-grade dysplasia. Post-LRYGB, 6 of 14 (42.9%) patients had histologic regression of BE to normal esophageal mucosa, with no evidence of ongoing BE. 13 of 14 patients (92.8%) reported compliance with continuing PPI therapy for at least the first year after surgery. Body mass index for the group of 14 patients improved from 46.6 to 30.3kg/m2. We recommend LRYGB as an effective combined bariatric and anti-reflux surgical procedure for patients with severe obesity and BE. In short-term follow-up, LRYGB achieved endoscopic and histologic regression to normal mucosa in a substantial number of the patients in our series. Long-term follow-up for patients with BE according to standard surveillance protocols is still recommended.

Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.

BackgroundRecruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention.MethodsThe By‐Band study was designed in the UK in 2009–2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux‐en‐Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation.ResultsThe pilot phase recruited over 13 months in 2013–2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder.ConclusionAdaptation of a two‐group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).

Body mass index is associated with region-dependent metabolic reprogramming of adipose tissue

Adipose tissue (AT) is involved in dysmetabolism pathogenesis. Regional fat distribution and functioning may contribute to obesity-related metabolic disorders and adverse health outcomes. Specific fat depots are suggested to possess unique biological properties, but specific metabolic profiles of subcutaneous (SAT) and visceral adipose tissue (VAT) remain unknown. We aimed to characterize VAT and SAT glucose metabolism, and their correlation with body mass index (BMI). AT samples from patients (n=12; F:M, 9:3) with a mean age of 46years (26–83years) and an average BMI of 29.6kg/m2 (18–37kg/m2) were used. VAT and SAT explants were obtained during elective laparoscopy, either cholecystectomy for uncomplicated cholelithiasis or gastric bypass for severe obesity. Explants were placed in insulin-free cell culture media and their metabolic profile was established by proton nuclear magnetic resonance. AT explants display a glucose and pyruvate consumption and acetate production that is region-dependent according to the patients BMI. In VAT, glucose consumption was positively correlated with BMI, while alanine and lactate production were negatively correlated with BMI, whereas in SAT the patients BMI did not affect AT secretome suggesting that increased BMI promotes a metabolic reprogramming of VAT towards de novo lipogenesis. This region-dependent metabolic reprogramming of AT associated with BMI was autonomous of insulin. This data, although preliminary, suggests that there is a BMI-related remodeling of glucose metabolism in VAT. Targeting this BMI-induced metabolic shift may represent a potential target to counteract unwanted consequences derived from visceral adiposity.

Body composition and bone health in adolescents after Roux-en-Y gastric bypass for severe obesity.

Laparoscopic Roux-en-Y gastric bypass (RYGB) causes changes in body composition and bone metabolism, yet little is known about effects in adolescents. The objective of this study was to report dual-energy X-ray absorptiometry measures and serum bone markers, hypothesizing that bone turnover increases after surgery. Inclusion criteria included the following: age 13-18 years and body mass index (BMI) >35 kg/m2 . Seventy-two adolescents (22 boys; mean age 16.5 years; BMI 44.8 kg/m2 ) undergoing RYGB underwent dual-energy X-ray absorptiometry and serum bone marker analyses preoperatively and annually for 2 years. Mean BMI reduction at 2 years was 15.1 kg/m2 . Body composition changes included a reduction in fat mass (51.8% to 39.6%, p < 0.001) and relative increase in lean mass (47.0% to 58.1%, p < 0.001). In contrast to previous studies in adults, adolescent boys lost a greater percentage of their body fat than girls (-17.3% vs. -9.5%, p < 0.001). Individual bone mineral density Z-scores (BMD-Z) at baseline were within or above the normal range. The mean (SD) BMD-Z was 2.02 (1.2) at baseline, decreasing to 0.52 (1.19) at 2 years. Higher concentrations of serum CTX (p < 0.001) and osteocalcin (p < 0.001) were observed in boys throughout the study period. Levels rose in the first year, before decreasing modestly in the second. Levels of serum markers of bone synthesis and resorption were higher in boys, whose skeletal maturity occurs later than girls'. Differences in body fat and lean mass proportions were observed according to sex following RYGB. Bone turnover increased, and BMD decreased to levels approaching a norm for age. Long-term outcome will determine the clinical relevance.

Effect of probiotics on postoperative quality of gastric bypass surgeries: a prospective randomized trial

BackgroundGastric bypass surgery is the recommended treatment for severely obese patients. However, postoperative symptomatic gastrointestinal (GI) episodes are common complaints. ObjectivesTo determine if administration of probiotics improves symptomatic GI episodes after gastric bypass surgery. SettingHospital-based bariatric center. MethodsThis double-blind, randomized trial was conducted between March 2010 and September 2010 with 60 patients who underwent gastric bypass for severe obesity and experienced postoperative symptomatic GI episodes. Patients were randomly assigned to the probiotics group A (n = 20; 1 g Clostridium butyricum MIYAIRI twice daily); probiotics group B (n = 20; Bifidobacterium longum BB536 twice daily); or digestive enzymes group (n = 20; Aczym, containing 100 mg takadiastase N, 20 mg cellulase AP, 50 mg lipase MY, and 100 mg pancreatin, twice daily). Quality of life was measured using the modified Gastrointestinal Quality of Life Index (mGIQLI) before and after the 2-week intervention. ResultsPreintervention patient characteristics and mGIQLI scores were similar among the 3 groups. After the 2-week intervention, the mean mGIQLI score improved from 57.4 to 63.9 points in the entire sample and also within each group for 7 items specifically for 7: excessive passage of gas, foul smell of flatulence, belching, heartburn, abdominal noises, abdominal bloating, and abdominal pain. ConclusionsAdministration of probiotics or digestive enzymes may improve symptomatic GI episodes after gastric bypass surgeries and improve quality of life, at least initially.

Temperament and one-year outcome of gastric bypass for severe obesity

BackgroundThe role of temperament traits in shaping the outcome of gastric bypass for severe obesity has not been established yet. This study evaluated whether temperament traits influence weight loss 1 year after gastric bypass, controlling for the potential confounding effect of Axis I and II disorders. MethodsForty-nine patients with severe obesity (body mass index = 46.4±6.7) undergoing gastric bypass completed a thorough psychiatric evaluation before surgery, including structured interviews, rating scales, and questionnaire assessing the presence and severity of co-morbid Axis I and II disorders. Temperament was evaluated with the Temperament and Character Inventory (TCI). Weight loss 1 year after surgery was calculated as percent total weight loss (%TWL). Predictors of weight loss were investigated with multivariate linear hierarchical regression. ResultsAfter accounting for psychiatric covariates, higher TCI persistence scores independently predicted 1-year outcome of gastric bypass and explained 40% of the variance in %TWL. Patients with low persistence scores showed a significantly lesser weight loss than patients with high scores. ConclusionTemperament traits denoting the ability to persevere in one’s goals in spite of immediate frustration (persistence) are associated with greater weight loss 1 year after gastric bypass. These data suggest the utility of preoperatively assessing and reinforcing such capacity to optimize surgical outcome. Future research will clarify the behavioral mechanisms mediating this relationship as well as the influence of temperament on weight maintenance.

Screening Postoperative Bariatric Patients for Marginal Ulcerations

Weight-loss surgery is one of the fastest growing major surgeries in the United States ( 1 Shikora S.A. Kim J.J. Tarnoff M.E. Nutrition and gastrointestinal complications of bariatric surgery. Nutr Clin Pract. 2007; 22: 29-40 Google Scholar ). In recent years, weight-loss surgery has increased by more than 600% ( 1 Shikora S.A. Kim J.J. Tarnoff M.E. Nutrition and gastrointestinal complications of bariatric surgery. Nutr Clin Pract. 2007; 22: 29-40 Google Scholar ). As of 2005, the most frequently performed weight-loss surgery has been the Roux-en-Y gastric bypass surgery (RYGB), accounting for approximately 85% of all weight-loss surgery performed in the United States ( 2 Schauer P. Gastric bypass for severe obesity: Approaches and outcomes. Surg Obes Relat Dis. 2005; 1: 297-300 Google Scholar ). The RYGB procedure involves reducing the stomach to a gastric volume of 15 to 30 mL ( 3 Mulholland M.W. Lillemoe K.D. Doherty G.M. Maier R.V. Upchurch G.R. Greenfield's Surgery: Scientific Principle and Practice. 4th ed. Lippincott Williams & Wilkins, Philadelphia, PA2006 Google Scholar ). The Roux-en-Y configuration consists of an intestine limb connected to the small gastric pouch (gastrojejunostomy), which prevents the bile from entering the newly formed stomach pouch and esophagus (Figure 1) ( 3 Mulholland M.W. Lillemoe K.D. Doherty G.M. Maier R.V. Upchurch G.R. Greenfield's Surgery: Scientific Principle and Practice. 4th ed. Lippincott Williams & Wilkins, Philadelphia, PA2006 Google Scholar ). The purpose of RYGB surgery is to decrease gastric volume and induce a substantial weight loss in morbidly obese individuals who have failed previous nonsurgical weight-loss attempts and who are suffering from weight-related comorbidities ( 4 Buchwald H. Consensus conference statement bariatric surgery for morbid obesity: Health implications for patients, health professionals, and third-party payers. Surg Obes Relat Dis. 2005; 1: 371-381 Google Scholar ). It is estimated that within the first 6 months postoperatively, RYGB surgery patients lose approximately one half of their excess weight ( 4 Buchwald H. Consensus conference statement bariatric surgery for morbid obesity: Health implications for patients, health professionals, and third-party payers. Surg Obes Relat Dis. 2005; 1: 371-381 Google Scholar ). S. Benson-Davies is a nutrition consultant in private practice in Spearfish, SD. D. R. Quigley is a general surgeon, Queen City Regional Medical Center, Spearfish, SD.

The cost-effectiveness of bariatric surgery.

The purpose of the study was to estimate the cost-effectiveness of gastric bypass in the treatment of severe obesity (body mass index > 40). A deterministic decision analysis that compared the lifetime expected costs and outcomes between open gastric bypass and no treatment of severe obesity from the payer perspective was performed. Men and women between the ages of 35 and 55 yr, with body mass index between 40 and 50 kg/m(2), who did not have cardiac disease and who failed conservative treatment, including pharmacotherapy, were included. Cost-effectiveness ratio of the base case conditions was made with parameter estimates from the literature and expert discussion and expressed as cost per quality-adjusted life-years (QALY). One- and two-way sensitivity analyses were performed on selected variables. Gastric bypass was not cost-saving, because the reduction in lifetime medical costs was less than the cost of treatment in any subgroup. The base case cost-effectiveness ratios ranged from 5,400 US dollars to 16,100 US dollars for women and from 10,700 US dollars to 35,600 US dollars per QALY for men. Sensitivity analysis demonstrated that in older, less obese men, the cost effectiveness ratio was responsive to the amount of weight lost, obesity-related quality of life, and complication rates. Parameter variation did not significantly affect cost-effectiveness ratios in the remaining patients. The authors concluded that gastric bypass is a cost-effective alternative to no treatment in the severely obese, at less than 50,000 US dollars per QALY.

The cost-effectiveness of bariatric surgery: Craig BM, Tseng DS. Cost-Effectiveness of Gastric Bypass for Severe Obesity, Am J Intern Med 2002;113:491–8

The purpose of the study was to estimate the cost-effectiveness of gastric bypass in the treatment of severe obesity (body mass index > 40). A deterministic decision analysis that compared the lifetime expected costs and outcomes between open gastric bypass and no treatment of severe obesity from the payer perspective was performed. Men and women between the ages of 35 and 55 yr, with body mass index between 40 and 50 kg/m 2, who did not have cardiac disease and who failed conservative treatment, including pharmacotherapy, were included. Cost-effectiveness ratio of the base case conditions was made with parameter estimates from the literature and expert discussion and expressed as cost per quality-adjusted life-years (QALY). One- and two-way sensitivity analyses were performed on selected variables. Gastric bypass was not cost-saving, because the reduction in lifetime medical costs was less than the cost of treatment in any subgroup. The base case cost-effectiveness ratios ranged from $5,400 to $16,100 for women and from $10,700 to $35,600 per QALY for men. Sensitivity analysis demonstrated that in older, less obese men, the cost effectiveness ratio was responsive to the amount of weight lost, obesity-related quality of life, and complication rates. Parameter variation did not significantly affect cost-effectiveness ratios in the remaining patients. The authors concluded that gastric bypass is a cost-effective alternative to no treatment in the severely obese, at less than $50,000 per QALY.

Cost-effectiveness of gastric bypass for severe obesity

Purpose To estimate the cost-effectiveness of gastric bypass in the treatment of severe obesity. Subjects and methods We performed a cost-effectiveness analysis of gastric bypass versus no treatment from the payer perspective. We discounted quality-adjusted life-years (QALYs), life-years, and cost during the patient’s lifetime. Our target group comprised women and men aged 35 to 55 years with a body mass index between 40 and 50 kg/m 2, and who did not have cardiovascular disease and in whom conservative bariatric therapies had been unsuccessful. Results The base case cost-effectiveness ratios ranged from $5000 to $16,100 per QALY for women and from $10,000 to $35,600 per QALY for men, depending on age and initial body mass index. In a few subgroups of older, less obese men, variation in parameters such as loss of excess weight, obesity-related quality of life, complication rates, and perioperative mortality affected the cost-effectiveness ratios. Parameter variation did not result in meaningful changes in the remaining patients. Conclusion Gastric bypass is a cost-effective alternative to no treatment, providing substantial lifetime benefits in patients who are severely obese.

Weight Loss and Food Intake 18 Months following Vertical Banded Gastroplasty or Gastric Bypass for Severe Obesity.

BACKGROUND: vertical banded gastroplasty (VBG) and gastric bypass Roux-en-Y (GBP) are adjunctive to lifelong commitment to energy restricted diet in the attempt by the severely obese to lose weight and maintain weight loss. METHODS: the outcome of 48 subjects (36 VBG and 12 GBP) is presented. RESULTS: 18 months nutritional counseling and follow-up indicated VBG and GBP to be equally effective in maintaining appreciable weight loss. Achievement of 'functional weight', such as minimum 50% loss of excess body weight for at least 12 months Post-operatively occurred in the majority of patients. Excess weight loss by GBP and VBG was 77% and 54% respectively during the first 6 months, with 7-15% additional loss during the next 12 months. BMI decreased from an average 43 to 27 kg m(2) after 12 months. During the first 3 months, energy intake was approximately 2930 kJ, increasing to;4605 kJ at 6 months, to; 5860 kJ at 12 months and then stabilizing. Intake of;50% of the Recommended Daily Allowance (RDA) for most vitamins and minerals was reached. Hemoglobin, iron, folic acid and thiamin values were in the normal range for the entire 18 months follow-up, while serum vitamin B12 levels decreased to deficiency levels during the same period. The pre-operative moderately elevated triglycerides, cholesterol, glucose and insulin levels returned to normal range, thereby alleviating the need for medication and reducing the risk of obesity-related morbidity. Most subjects were quickly satiated with small amounts of solid foods and did not report hunger feelings for the first 6 months post-operatively. The main significant changes in food preferences in the first 6 months were the decrease in starch-based products and the increase in semi-solid milk products and eggs. CONCLUSION: taken together these observations suggest that the subjects should be strongly advised to partake in structured counseling for an extended period of time.