Bariatric research Discussion

Running Head: BARIATRIC RESEARCH 1 Bariatric Surgery Patients Ingrid Valerio West Coast University Running Head: BARIATRIC RESEARCH 2 Essentially, research involving humans has rules intended to protect individuals, their right to choose and privacy. For this research, the focus will be considering how these laws apply to bariatric patients. Depict the rules for directing involvement in this study of human subjects under strictest ethical standards. For any given research, it is proper that ethics are observed by all means as this is the only way that one can get to have the desired outcomes. In a situation where ethics are not factored in, especially when dealing with humans, the transparency, trust and objectivity is lost due to the violation of individuals and their trust. Some people might feel either disrespected or just choose to give false data hence leading to wrong results (Wimmelmann, 2013). The respect for people assumes the behavior of individuals and the respect and thought they are expected. It includes the involvement of people needed in research straightforwardly as Respect for People perceives the characteristic estimation of people and the respect and thought that they are expected. It incorporates the treatment of people required in research straightforwardly as members and the individuals who are members on the grounds that their information or human natural materials, which for the reasons for this Policy incorporate materials identified with human multiplication, are utilized as a part of research. Respect for People fuses the double good commitments to respect self-governance and to ensure those with creating debilitated or lessened self-sufficiency (Wimmelmann, 2013). Recruitment incorporates the capacity to ponder about a choice and to act in light of that consultation. Respecting self-governance implies giving due yielding to the individuals judgment and guaranteeing that the individual is allowed to participate and consent sharing personal information. Self-sufficiency is not practiced in segregation but rather is impacted by a man’s Running Head: BARIATRIC RESEARCH 3 different associations with family, to the group, and to social, social, etymological, religious and different gatherings. Similarly, a man’s choices can affect any of these associations (Funk, 2015). To begin with, standards advance the points of research, for example, learning, truth, and shirking of blunder. For instance, denials against manufacturing, distorting, or distorting research information advance reality and limit mistake. Second, since research frequently includes a lot of participation and coordination among a wide range of individuals in various orders and foundations, moral models advance the qualities that are fundamental to collective work, for example, put stock in, responsibility, shared respect, and decency (Funk, 2015). Bariatric research Discussion

For the recruitment process, recruiting emails would be sent to an email list of a specific intrigue aggregate or an email list of a specific association. The cost is low and, if your list contains countless, it could without much of a stretch help you to enlist a decent number of research members (Pera, 2012). In any case, reaction weariness is a specific hazard with this strategy. Over-abusing individuals on those lists by sending rehashed recruitment messages can bring about the enrollment specialist being hailed as a wellspring of spam. Essentially, acquiring on the web internet searcher promotions empower you to enroll members who scan for particular watchwords. Clients’ conduct is the most grounded flag of their interests, consequently, the statistical surveying group can be sure that the members they enroll are for the most part liable to fit the profile they have at the top of the priority list. The exploration will be directed in two orderly hunts of English dialect writing in MEDLINE. The first will be on information accumulation registries identified with WLS; the second one being an extended hunt including other surgical fields, for example, heart and Running Head: BARIATRIC RESEARCH thoracic surgery and registries, for instance, growth. A profound hunt will be done to think of articles that are apropos (Pera, 201). Information will be removed, and confirm classes allocated as per an evaluating framework in view of set up confirmation based models. Suggestions ought to be gotten from these writing audits and expert opinion. 4 Running Head: BARIATRIC RESEARCH 5 Running Head: BARIATRIC RESEARCH 6 References Running Head: BARIATRIC RESEARCH Funk, L. M., et al. “A health service research agenda for bariatric surgery in the Veterans Health Administration.” 32.1 (2015): 65-69. MCKIE, A. (2013). ETHICS IN HEALTHCARE RESEARCH. The Fundamental of Nursing and Health care Researches, 229. Pera, S. A. (2012 ). Ethics in healthcare. Juta and Company Ltd. Wimmelmann, L. Mortensen. “Psychological prediction of the mental health-related quality of life following bariatric surgery (2013): the review of the recent researches.”. Tappen, R. M. (2016). Advanced Nursing Research, 2nd Edition. [Bookshelf Online]. Retrieved from https://online.vitalsource.com/#/books/9781284132496/ 7 Running Head: BARIATRIC RESEARCH 8 Bariatric research Discussion

Running Head: BARIATRIC RESEARCH 9 International Journal of Obesity (2014) 38, 1410–1415 © 2014 Macmillan Publishers Limited All rights reserved 0307-0565/14 www.nature.com/ijo ORIGINAL ARTICLE Effect of bariatric surgery on microvascular dysfunction associated to metabolic syndrome: a 12-month prospective study JF Martín-Rodríguez1,5, A Cervera-Barajas2,5, A Madrazo-Atutxa1, PP García-Luna1, JL Pereira1, J Castro-Luque3, A León-Justel3, S Morales-Conde4, JR Castillo2, A Leal-Cerro1,5 and DA Cano1,5 OBJECTIVE: To prospectively evaluate the effect of weight loss after bariatric surgery on microvascular function in morbidly obese patients with and without metabolic syndrome (MetS). METHODS: A cohort of morbidly obese patients with and without MetS was studied before surgery and after 12 months of surgery. Healthy lean controls were also examined. Microvascular function was assessed by postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated from laser-Doppler skin blood flow and blood pressure. Regression analysis was performed to assess the contribution of different clinical, metabolic and biochemical parameters to microvascular function. RESULTS: Before surgery, 62 obese patients, 39 with MetS and 23 without MetS, and 30 lean control subjects were analyzed. The absolute area under the hyperemic curve (AUCH) CVC of PORH was significantly decreased in obese patients compared with lean control subjects. One year after surgery, AUCH CVC significantly increased in patients free of MetS, including patients that had MetS before surgery. In contrast, AUCH CVC did not significantly change in patients in whom MetS persisted after surgery. Stepwise multivariate regression analysis showed that only changes in HDL cholesterol (HDL-C) and oxidized LDL (oxLDL) independently predicted improvement of AUCH after surgery. These two variables together accounted for 40.9% of the variability of change in AUCH CVC after surgery. CONCLUSIONS: Bariatric surgery could significantly improve microvascular dysfunction in obese patients, but only in patients free of MetS after surgery. Improvement of microvascular dysfunction is strictly associated to postoperative increase in HDL-C levels and decrease in oxLDL levels. International Journal of Obesity (2014) 38, 1410–1415; doi:10.1038/ijo.2014.15 Keywords: bariatric surgery; HDL-cholesterol; laser Doppler flowmetry; metabolic syndrome; microvascular dysfunction; oxidized LDL INTRODUCTION Obesity is characterized by impaired microvascular and macrovascular function that may contribute to increased risk of cardiovascular disease.1 Clinical and experimental evidence suggest that microvascular dysfunction is a potential factor explaining the association among obesity, hypertension and insulin resistance, which are major cardiovascular risk factors.2,3 Several methods are used to assess microvascular function in clinical research.4 Postocclusive reactive hyperemia (PORH) at forearm skin evaluated by laser Doppler flowmetry (LDF) has been widely used to assess microvascular function due to its noninvasive nature. PORH is the sudden rise in skin blood flow after release of a brief arterial occlusion and provides an overall measurement of microvascular function.5 However, concerns about the reproducibility of this method have been recently 1 raised.5 In particular, reproducibility studies of LDF in obese patients are scarce. Bariatric research Discussion

Bariatric surgery has emerged as an effective treatment for morbid obesity on the basis of both its efficacy6 and beneficial effects on obesity-related comorbidities and total mortality.7–9 It has been previously shown that bariatric surgery could reverse microvascular dysfunction in obese patients although the determinants that mediate this improvement in microvascular function have not been identified.10–14 Bariatric surgery-induced weight loss also ameliorates the metabolic syndrome (MetS), a group of clinical manifestations that includes obesity, hypertension, insulin resistance and dyslipidemia.15 Interestingly, the association between surgically induced improvement in microvascular function and metabolic syndrome has not been previously investigated. Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain; 2Unidad de Ensayos Clínicos, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 3Unidad de Bioquímica Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain and 4Unit of Innovation in Minimally Invasive Surgery, Unidad de Gestión Clínica de Cirugía, Hospital Universitario Virgen del Rocío, Sevilla, Spain. Correspondence: Dr DA Cano or Dr A Leal-Cerro, Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Avda. Manuel Siurot, s/n, Sevilla 41013, Spain. E-mail: dcano-ibis@us.es or alealcerro@us.es 5 These authors contributed equally to this work. Received 14 October 2013; revised 17 December 2013; accepted 17 January 2014; accepted article preview online 28 January 2014; advance online publication, 25 February 2014 Bariatric surgery and microvascular dysfunction JF Martín-Rodríguez et al 1411 The purpose of this study was to investigate the effect of surgically induced weight loss on microvascular function in morbidly obese patients with and without MetS. More specifically, we wanted to determine whether changes in microvascular function after bariatric surgery are associated to resolution of MetS. To this end, we prospectively evaluated microvascular function by LDF in morbidly obese patients with and without MetS before and 12 months after bariatric surgery. Bariatric research Discussion

We also assessed the contribution of different clinical, metabolic and biochemical parameters to surgically induced improvement in microvascular function. MATERIALS AND METHODS Study design and subjects Obese subjects were recruited from the waiting list for bariatric surgery of the Surgery Unit at Hospital Universitario Virgen del Rocío from November 2009 to March 2011. All obese patients were required to meet NIH guidelines for eligibility for bariatric surgery: BMI ⩾40 kg m−2 or ⩾35 kg m − 2 with comorbidities (that is, diabetes, hypertension, dilated cardiomyopathy or sleep apnea).16 The inclusion criteria were male and female patients aged 16–65 years, and agreement to participate in the study by providing a signed consent form. The patients with arterial hypertension, diabetes, cardiomyopathy and sleep apnea were under medical treatment for these obesity complications at the time of the evaluation. Exclusion criteria included acute or chronic inflammatory disease, malignant disease, asthma or any history of alcohol or drug abuse. The experimental protocol was approved by the Ethical Committee of the Hospital Universitario Virgen del Rocío. All participants provided written informed consent to participate in the study. Additional written informed consent was obtained after the surgical procedure. Obese patients were grouped as patients with MetS or without MetS on the basis of the definition of MetS proposed by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults Panel III.17 Patients fulfilling three or more of the following criteria were considered as having MetS: (1) central obesity (waist circumference >102 cm in men or >88 cm in women); (2) high blood pressure of 130/85 mm Hg or greater or use of antihypertensive therapy; (3) high fasting glucose (⩾110 mg dl − 1); (4) hypertriglyceridemia (⩾150 mg dl − 1) and (5) low high-density lipoprotein cholesterol (HDLc) (o 40 mg dl − 1 for males or o 50 mg dl − 1 for females). Each subject made a visit at baseline and 12 months after the bariatric surgery. For the 12-month follow-up study, patients in the group with MetS before surgery were further subdivided into two subgroups: patients in whom MetS resolved after surgery and patients in whom MetS persisted after surgery. Healthy lean control subjects were also recruited as a comparison group for the evaluations before surgery. Post-occlusive forearm skin reactive hyperemia (PORH) measurements Studies were performed in the morning in a quiet, temperature-controlled room (22–24 °C). Subjects were asked to avoid smoking and caffeine- and alco hol-containing drinks for 24 h, and from performing vigorous exercises for at least 12 h before the test. Bariatric research Discussion

Measurements were taken with subjects in a supine position. On the preoperative study, LDF test was performed two weeks before the surgery. Changes in cutaneous blood flow (flux) was measured by a commercial single-point laser Doppler flowmetry device (Periflux 5000; bandwidth of 15 kHz, Perimed AB, Järfälla, Sweden) with a thermostatic laser Doppler probe (Probe 481-1, Perimed AB, Järfälla, Sweden). The probe has a fiber separation of 0.25 mm and collects perfusion data at a depth of about 0.5–1 mm. Blood flow data were recorded continuously at a sample rate of 40 recordings per second. Data from the laser Doppler perfusion monitor were analyzed using PeriSoft for Windows, version 2.5.5 (Perimed AB, Järfälla, Sweden). Data files were processed for conversion from mV to PU (perfusion units) by division with the gain factor of the instrument (10 mV PU − 1). The laser Doppler probe was placed on the volar surface of the right forearm, 10 cm proximal to the wrist. This position was marked so that exactly the same site was used in all measurements. After a baseline measurement of 3 min, the brachial artery was occluded using a pressure cuff placed around the right upper arm that was inflated to 220 mm Hg. Inflating the cuff took less than 5 s. This local ischemia was held for 4 min, and then deflated. Deflating the cuff was practically instantaneous (o40 mm Hg within 0.2 s). The flux recording was continued for at least 5 min (until the signal reaches the baseline flux). Five different PORH parameters were analyzed (Supplementary Figure 1). The value of skin flux at baseline is defined as the average value of the 3-minute baseline period before occlusion. Maximum response (PORHmax) was defined as the maximum absolute change (PORHpeak) from baseline.19 The area under the hyperemic curve (AUCH) was calculated from the time the cuff was released until the end of the measurement. The area under the occlusion curve (AUCO) was calculated from the time the occlusion started until the end of the occlusion. These five parameters were subsequently transformed into cutaneous vascular conductance (CVC), calculated as the flux divided by the mean arterial pressure in mm Hg. Mean arterial pressure was calculated as (2/3(diastolic blood pressure) + 1/3(systolic blood pressure)). To determine the reproducibility of laser Doppler-derived parameters in the measurement of PORH in obese patients, a study of reproducibility was performed before and after bariatric surgery. Specifically, we investigated within-subject reproducibility of the PORH parameters, that is, reproducibility and variability between measurements. These measurements were performed at different times: (0, 15 min and 24 h after the first measurement). For comparison among groups, we used data from measurements at time 0. All measurements were performed by the same investigator. Statistical methods Clinical and biochemical measurements Clinical and biochemical measurements were performed before surgery (two weeks earlier) and 12 months after surgery. Every measurement was performed after an overnight fast of 10 h. Systolic and diastolic blood pressure was measured right before LDF evaluation. The values were the mean of two measurements with subjects in sitting position. Measures of weight, height, and waist and hip circumferences were also obtained. Bariatric research Discussion

Blood samples were drawn from an antecubital vein. Plasma glucose, total serum cholesterol, high-density lipoprotein and triglycerides were measured using a Cobas C chemistry analyzer (Roche Diagnostics, Mannheim, Germany). The Friedewald equation was used to calculate LDL cholesterol (LDLc) from total serum cholesterol, HDLc and triglycerides.18 Plasma insulin was measured by electrical chemiluminescence immunoassay using an ElecsysE170 (Roche Diagnostics, Mannheim, Germany). Hemoglobin A1c (HbA1c) was measured by high-pressure liquid chromatography using a Variant II analyzer (BioRad Laboratories, Hercules, CA, USA) The index of insulin resistance (HOMA) was calculated using the formula: glucose (mmol l − 1)× insulin (μU ml −1)/22.5. Plasminogen activator inhibitor-1 (PAI-1) concentrations were determined by enzyme-linked immunosorbent assay (American Diagnostica Inc., Stamford, CT, USA). Ultrasensitive C-reactive protein (CRP) was measured with the CardioPhase hsCRPkit (Dade Behring, Marburg, Germany), the intra and interassay CVs being 2.8 and 4.6%, respectively. Oxidized low-density lipoprotein (oxLDL) was measured with the ELISA kit (Immunodiagnostic Systems, Boldon, UK). The intra and interassay CV was 3.9 and 9%, respectively. © 2014 Macmillan Publishers Limited Results are shown as the mean± s.d. or median and interquartile range unless otherwise noted. Between-group differences in normally distributed data were assessed by one-way analysis of variance (ANOVA) followed by the Fisher’s multiple comparison tests to identify differences between groups.

For non-normally distributed data, comparisons between groups were analyzed by the Kruskal–Wallis test with Dunn’s multiple comparison tests. To analyze changes after bariatric surgery, the two-way ANOVA for repeated measures was chosen with post hoc Tukey’s comparisons. The contribution of clinical and biochemical parameters to variation in microvascular function was assessed by multivariate regression analysis. Statistically significant predictors were included in the models with a stepwise procedure, after adjusting for age and gender, and antihypertensive and diabetic treatment. Two-sided P-values were assessed for all models. Only variables that had a Po0.05 were included in the final model. To determine the repeatability of LDF, the intraclass correlation coefficients were calculated. Values of intraclass correlation coefficient more than 0.80 were considered excellent agreements.20 To examine t … Bariatric research Discussion