The burden of proof: the current state of atrial fibrillation prevention and treatment trials

Atrial fibrillation (AF) is an age-related arrhythmia of enormous socioeconomic significance. In recent years, our understanding of the basic mechanisms that initiate and perpetuate AF has evolved rapidly, catheter ablation of AF has progressed from concept to reality, and recent studies suggest lifestyle modification may help prevent AF recurrence. Emerging developments in genetics, imaging, and informatics also present new opportunities for personalized care. However, considerable challenges remain. These include a paucity of studies examining AF prevention, modest efficacy of existing antiarrhythmic therapies, diverse ablation technologies and practice, and limited evidence to guide management of high-risk patients with multiple comorbidities. Studies examining the long-term effects of AF catheter ablation on morbidity and mortality outcomes are not yet completed. In many ways, further progress in the field is heavily contingent on the feasibility, capacity, and efficiency of clinical trials to incorporate the rapidly evolving knowledge base and to provide substantive evidence for novel AF therapeutic strategies. This review outlines the current state of AF prevention and treatment trials, including the foreseeable challenges, as discussed by a unique forum of clinical trialists, scientists, and regulatory representatives in a session endorsed by the Heart Rhythm Society at the 12th Global CardioVascular Clinical Trialists Forum in Washington, DC, December 3–5, 2015

A Clinical-Genetic Score for Predicting Weight Loss after Bariatric Surgery: The OBEGEN Study

Genética; Obesidad; Pérdida de pesoGenetics; Obesity; Weight lossGenètica; Obesitat; Pèrdua de pesAround 30% of the patients that undergo bariatric surgery (BS) do not reach an appropriate weight loss. The OBEGEN study aimed to assess the added value of genetic testing to clinical variables in predicting weight loss after BS. A multicenter, retrospective, longitudinal, and observational study including 416 patients who underwent BS was conducted (Clinical.Trials.gov- NCT02405949). 50 single nucleotide polymorphisms (SNPs) from 39 genes were examined. Receiver Operating Characteristic (ROC) curve analysis were used to calculate sensitivity and specificity. Satisfactory response to BS was defined as at nadir excess weight loss >50%. A good predictive model of response [area under ROC of 0.845 (95% CI 0.805–0.880), p < 0.001; sensitivity 90.1%, specificity 65.5%] was obtained by combining three clinical variables (age, type of surgery, presence diabetes) and nine SNPs located in ADIPOQ, MC4R, IL6, PPARG, INSIG2, CNR1, ELOVL6, PLIN1 and BDNF genes. This predictive model showed a significant higher area under ROC than the clinical score (p = 0.0186). The OBEGEN study shows the key role of combining clinical variables with genetic testing to increase the predictability of the weight loss response after BS. This finding will permit us to implement a personalized medicine which will be associated with a more cost-effective clinical practice.This research was supported by grants from the “Pla Estratègic de Recerca i Innovació en Salut” (PERIS) 2016–2020 (SLT002/16/00497), the Instituto de Salud Carlos III (PI PI18/00964), Fondos FEDER “Una manera de hacer Europa”), and Menarini España. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is an initiative of the Instituto Carlos III

Development and validation of a scoring system for pre-surgical and early post-surgical prediction of bariatric surgery unsuccess at 2&#160;years

Bariatric surgery (BS) is an effective treatment for morbid obesity. However, a simple and easy-to-use tool for the prediction of BS unsuccess is still lacking. Baseline and follow-up data from 300 consecutive patients who underwent BS were retrospectively collected. Supervised regression and machine-learning techniques were used for model development, in which BS unsuccess at 2 years was defined as a percentage of excess-weight-loss (%EWL) < 50%. Model performances were also assessed considering the percentage of total-weight-loss (%TWL) as the reference parameter. Two scoring systems (NAG-score and ENAG-score) were developed. NAG-score, comprising only pre-surgical data, was structured on a 4.5-point-scale (2 points for neck circumference ≥ 44 cm, 1.5 for age ≥ 50 years, and 1 for fasting glucose ≥ 118 mg/dL). ENAG-score, including also early post-operative data, was structured on a 7-point-scale (3 points for %EWL at 6 months ≤ 45%, 1.5 for neck circumference ≥ 44 cm, 1 for age ≥ 50 years, and 1.5 for fasting glucose ≥ 118 mg/dL). A 3-class-clustering was proposed for clinical application. In conclusion, our study proposed two scoring systems for pre-surgical and early post-surgical prediction of 2-year BS weight-loss, which may be useful to guide the pre-operative assessment, the appropriate balance of patients’ expectations, and the post-operative care

Towards precision medicine in bariatric surgery prescription

Obesity is a complex, multifactorial and chronic disease. Bariatric surgery is a safe and effective treatment intervention for obesity and obesity-related diseases. However, weight loss after surgery can be highly heterogeneous and is not entirely predictable, particularly in the long-term after intervention. In this review, we present and discuss the available data on patient-related and procedure-related factors that were previously appointed as putative predictors of bariatric surgery outcomes. In addition, we present a critical appraisal of the available evidence on which factors could be taken into account when recommending and deciding which bariatric procedure to perform. Several patient-related features were identified as having a potential impact on weight loss after bariatric surgery, including age, gender, anthropometrics, obesity co-morbidities, eating behavior, genetic background, circulating biomarkers (microRNAs, metabolites and hormones), psychological and socioeconomic factors. However, none of these factors are sufficiently robust to be used as predictive factors. Overall, there is no doubt that before we long for precision medicine, there is the unmet need for a better understanding of the socio-biological drivers of weight gain, weight loss failure and weight-regain after bariatric interventions. Machine learning models targeting preoperative factors and effectiveness measurements of specific bariatric surgery interventions, would enable a more precise identification of the causal links between determinants of weight gain and weight loss. Artificial intelligence algorithms to be used in clinical practice to predict the response to bariatric surgery interventions could then be created, which would ultimately allow to move forward into precision medicine in bariatric surgery prescription

Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

Bariatric surgery is today the most effective long-term therapy for the management of patients with severe obesity, and its use is recommended by the relevant guidelines of the management of obesity in adults. Bariatric surgery is in general safe and effective, but it can cause new clinical problems and is associated with specific diagnostic, preventive and therapeutic needs. For clinicians, the acquisition of special knowledge and skills is required in order to deliver appropriate and effective care to the post-bariatric patient. In the present recommendations, the basic notions needed to provide first-level adequate medical care to post-bariatric patients are summarised. Basic information about nutrition, management of co-morbidities, pregnancy, psychological issues as well as weight regain prevention and management is derived from current evidences and existing guidelines. A short list of clinical practical recommendations is included for each item. It remains clear that referral to a bariatric multidisciplinary centre, preferably the one performing the original procedure, should be considered in case of more complex clinical situations

Towards personalized therapy in genetic obesity

The incidence of obesity worldwide is increasing persistently, together with its associated diseases such as diabetes mellitus. Prevention is by far the most important step. It is important to pay attention to (individual) obesity causing factors, such as changes in the genetic material. These can be divided into three categories: (1) monogenic syndromic obesity, in which obesity (caused by alterations in a single gene) is accompanied by congenital malformations, dysmorphic features and/or intellectual deficit; (2) monogenic non-syndromic obesity (caused by alterations in a single gene) affecting the food satiety centre in the brain by disturbance of the leptin-melanocortin pathway; and (3) polygenic obesity, in which the effect of DNA variations in multiple genes result together in a high risk for obesity. For patients with existing obesity, adequate treatment is requested to prevent further health damage. Besides alterations in eating habits and physical activity rate, metabolic surgery can be inevitable for some patients. The latter is currently the most effective treatment option for obesity in adults. It involves procedures to altering the anatomy of the gastrointestinal tract to induce metabolic changes and weight loss. The most frequent performed procedures are the Sleeve Gastrectomy (SG) and the Roux-en-Y Gastric Bypass (RYGB). Weight outcome varies widely and is thought to be a dynamic process. In the long term, in approximately 20-30% of the patients suboptimal weight loss or severe recurrent weight gain has been observed. One of the hypotheses is that the optimal weight response is negatively influenced by underlying obesity gene defects

Novel approaches in adolescent obesity management

This PhD thesis on adolescent obesity focuses on the role of medical professionals and the interventions that they provide for obesity. We undertook a feasibility and acceptability study to examine HELPclinic, a novel brief weight management intervention delivered by health professionals in a specialist obesity service. The intervention was shown to be feasible and acceptable. Four overlying themes were captured in participant interviews: HELPclinic relationships enabled discussions of a difficult topic; lack of novel medical approaches polarised participants’ acceptance of HELPclinic; School vs HELPclinic – it’s hard to do both; and ongoing support is crucial. Qualitative interviews with young people and their families taking anti-obesity drugs (AOD) resulted in three theoretic models to explain their experiences of AOD, relating to commencement, relationship between dosing and side-effects, and drug cessation. Use of anti-obesity drugs is challenging for many adolescents. Multiple factors were identified that could be targeted to improve concordance and maximise efficacy. A survey of GP AOD prescribing found low prescribing prevalence. Metformin was largely initiated by specialists for co-morbidities associated with obesity, and orlistat was largely initiated by GPs and outside NICE guidance. GPs reported lower confidence in AOD prescribing and wanted more support. 3 A systematic review of the psychological/social outcomes of bariatric surgery in adolescents found a small evidence base with few high quality studies and outcomes rare beyond 2 years post-surgery. Quality of life and depressive symptoms improved after surgery. We present the first UK report of the outcomes of a bariatric surgery clinical pathway. Of fifty patients assessed, 12% were not eligible for surgery, 14% actively opted out,16% were lost to follow-up and 58% underwent surgery. Mean age at surgery was 18.3 years and mean BMI 53.1 kg/m2. BMI outcomes and complications post-surgery were similar to those published in research cohorts. Follow-up was inconsistent and challenging

Influences of major weight loss in women treated with bariatric surgery on their partners’ and children’s weight and psychosocial functioning

The overall aim of the current PhD thesis was to explore how families of female bariatric surgery patients are affected by the surgery. The focus of the thesis was on differences in weight status in siblings born before and after maternal bariatric surgery, and on changes in weight and psychosocial functioning in partners and children of women undergoing Roux-en-Y gastric bypass (RYGB). Study I explored differences in BMI and prevalence of overweight and obesity at the ages of four, six and 10 in children born before and after maternal bariatric surgery. Results showed that at no age did the children born after surgery have a lower prevalence of overweight or obesity, and that there was no association between differences in maternal BMI at week 10 of the two pregnancies and differences in siblings’ BMI at age four. Study II focused on changes in female RYGB patients’ partners in terms of BMI, waist circumference, sleep quality, body dissatisfaction and symptoms of anxiety and depression. The results showed significant reductions in BMI and waist circumference in the partners. However, psychosocial variables, as measured by questionnaires, remained unchanged in the men. In Study III, differences in weight status, body esteem and self-concept in children of female RYGB patients were explored. It was found that the children had a reduced relative risk of overweight after maternal RYGB. The results also showed that the boys improved their age-adjusted body esteem slightly, whilst the girls did not. Study IV investigated changes in eating behaviour and food choices in female RYGB patients and their families. The women were shown to increase their cognitive restraint, decrease their uncontrolled and emotional eating, and reduce their intake frequency of soft drinks and sweets after surgery. Their partners, however, reported no changes in their eating behaviour and food choices. The boys’ eating behaviour improved following maternal RYGB, but the same was not true for the girls in the sample. The children who were overweight or obese at baseline also improved their eating behaviour in comparison to the normal weight children. In conclusion, this thesis shows that women’s gastric bypass surgery may be associated with positive changes in her partners’ and children’s weight, especially if they are themselves overweight. Changes in psychosocial functioning are smaller and more complex in the current sample, and require further study