Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis.

BACKGROUND: Weight reduction has been shown to alleviate symptoms of osteoarthritis of the knee, including pain. The effect of glucagon-like peptide-1 receptor agonists on outcomes in knee osteoarthritis among persons with obesity has not been well studied. METHODS: We conducted a 68-week, double-blind, randomized, placebo-controlled trial at 61 sites in 11 countries. Participants with obesity (a body-mass index [BMI; the weight in kilograms divided by the square of the height in meters] of ≥30) and a clinical and radiologic diagnosis of moderate knee osteoarthritis with at least moderate pain were randomly assigned, in a 2:1 ratio, to receive once-weekly subcutaneous semaglutide (2.4 mg) or placebo, in addition to counseling on physical activity and a reduced-calorie diet. The primary end points were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (on a scale of 0 to 100, with higher scores reflecting worse outcomes) from baseline to week 68. A key confirmatory secondary end point was the physical-function score on the 36-Item Short Form Health Survey (SF-36), version 2 (on a scale of 0 to 100, with higher scores indicating greater well-being). RESULTS: A total of 407 participants were enrolled. The mean age was 56 years, the mean BMI 40.3, and the mean WOMAC pain score 70.9. A total of 81.6% of the participants were women. The mean change in body weight from baseline to week 68 was -13.7% with semaglutide and -3.2% with placebo (P<0.001). The mean change in the WOMAC pain score at week 68 was -41.7 points with semaglutide and -27.5 points with placebo (P<0.001). Participants in the semaglutide group had a greater improvement in SF-36 physical-function score than those in the placebo group (mean change, 12.0 points vs. 6.5 points; P<0.001). The incidence of serious adverse events was similar in the two groups. Adverse events that led to permanent discontinuation of the trial regimen occurred in 6.7% of the participants in the semaglutide group and in 3.0% in the placebo group, with gastrointestinal disorders being the most common reason for discontinuation. CONCLUSIONS: Among participants with obesity and knee osteoarthritis with moderate-to-severe pain, treatment with once-weekly injectable semaglutide resulted in significantly greater reductions in body weight and pain related to knee osteoarthritis than placebo. (Funded by Novo Nordisk; STEP 9 ClinicalTrials.gov number, NCT05064735.).

Distinct T cell subsets in adipose tissue are associated with obesity.

Adipose tissue inflammation is a driving factor for the development of obesity-associated metabolic disturbances, and a role of adipose tissue T cells in initiating the pro-inflammatory signaling is emerging. However, data on human adipose tissue T cells in obesity are limited, reflected by the lack of phenotypic markers to define tissue-resident T cell subsets. In this study, we performed a deep characterization of T cells in blood and adipose tissue depots using multicolor flow cytometry and RNA sequencing. We identified distinct subsets of T cells associated with obesity expressing the activation markers, CD26 and CCR5, and obesity-specific genes that are potentially engaged in activating pro-inflammatory pathway, including ceramide signaling, autophagy, and IL-6 signaling. These findings increase our knowledge on the heterogeneity of T cells in adipose tissue and on subsets that may play a role in obesity-related pathogenesis.

Association of normal body mass index and weight loss with long-term major cardiovascular events after PCI for myocardial infarction.

Objectives: To investigate whether normal body mass index (BMI) shortly after percutaneous coronary intervention (PCI) for myocardial infarction is associated with increased risk of long-term major cardiovascular events (MACE), and to explore potential clinical determinants of long-term weight loss (WL) after PCI. Methods: Single-center cohort study with 5-year follow-up of patients treated with PCI for myocardial infarction between 2016 and 2018. Categorical WL was defined as > 0 kg body weight reduction from baseline to end of follow-up. Results: Of 236 patients (24% women), mean age was 64.9 ± 10.2 years and mean BMI within 4 days after PCI was 27.1 ± 4.3 kg/m2. Seventy-five patients (32%) had at least one MACE, equally distributed between those with normal weight (31%), overweight (32%), and obesity (31%). Patients with overweight or obesity had a lower crude mortality rate than their normal weight counterparts (7.4% vs 16.4%, p = 0.049), but the relative hazard of death did not differ from those with normal weight, HR 0.50, 95% CI 0.22-1.15. Patients with either a long-term WL (n = 112) or no WL (n = 95) had a comparable incidence of non-fatal MACE (27% vs 22%, p = 0.518). The proportion of patients reporting unintentional weight loss was significantly higher in the normal weight group (82%) compared with those with overweight (41%) or obesity (28%), p < 0.001. Conclusion: Our results did not confirm any association between normal BMI after PCI and long-term MACE. However, patients with normal BMI at baseline had a higher incidence of unintentional WL than those with elevated BMI. Trial registration: Current research information system in Norway (CRISTIN): ID 542528.

A pilot study of implementation of endoscopic sleeve gastroplasty (ESG) in Norway.

BACKGROUND AND AIM: Bariatric surgery is the most effective treatment for obesity but is invasive and associated with serious complications. Endoscopic sleeve gastroplasty (ESG) is a less invasive weight loss procedure to reduce the stomach volume by full-thickness sutures. ESG has been adopted in many countries, but implementation at Scandinavian centres has not yet been documented. We performed a clinical pilot trial at a Norwegian centre with the primary objective to assess the feasibility of the ESG procedure. PATIENTS AND METHODS: We included the first 10 patients treated with ESG at a Norwegian centre in a single-arm pilot study. The eligibility criteria were either a body mass index (BMI) of 40-49.9 kg/m2, BMI 35-39.9 kg/m2 and at least one obesity-related comorbidity, or BMI 30-34.9 kg/m2 and type 2 diabetes. Patient follow-up resembled the scheme used for bariatric surgery at the center, including dietary plans and outpatient visits. RESULTS: All procedures were technically successful except for one patient who had adhesions between the stomach and anterior abdominal wall, related to a prior hernia repair, resulting in less-than-intended stomach volume reduction. Mean total body weight loss (TBWL) after 26 and 52 weeks was 12.2% (95% CI 8.1-16.2) and 9.1% (95% CI 3.3 - 15.0). One patient experienced a minor suture-induced diaphragmatic injury, which was successfully managed conservatively. CONCLUSIONS: This first Scandinavian clinical trial of ESG, documenting the implementation of the procedure at a Norwegian center, demonstrated acceptable feasibility and safety, with large variations in individual weight loss during the 52-week follow-up period.

Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis : A Randomized Controlled Trial.

BACKGROUND: Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. OBJECTIVE: To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. DESIGN: Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tønsberg]). (ClinicalTrials.gov: NCT01778738). SETTING: Tertiary care obesity center in Norway. PARTICIPANTS: 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). INTERVENTION: From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. MEASUREMENTS: The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. RESULTS: Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. LIMITATIONS: Single-center study, short follow-up time, and lack of power for secondary outcomes. CONCLUSION: With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. PRIMARY FUNDING SOURCE: Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity.

AIM: Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. METHODS: This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. RESULTS: Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB -30 ± 6.9%, diet -3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference -0.30 [-0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. CONCLUSION: Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

BACKGROUND AND AIMS: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. PATIENTS AND METHODS: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. RESULTS: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. CONCLUSIONS: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study.

BACKGROUND: Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI). RESULTS: A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen's d = 0.75), and (0.7 [0.3-1.1], Cohen's d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. CONCLUSIONS: Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01778738.

Effect of aerobic exercise intensity on health-related quality of life in severe obesity: a randomized controlled trial.

BACKGROUND: Aerobic exercise is an important part of obesity treatment and may improve health-related quality of life (HRQOL). The objective of this study was to compare the effect of two different exercise programs on health-related quality of life in patients with severe obesity. METHODS: This was a single-center, open-label, randomized, parallel-group study comparing the effects of a 24-week moderate-intensity continuous training (MICT) program and a combined high-intensity interval training program with MICT (HIIT/MICT). The primary objective (specified secondary outcome) was to assess HRQOL by using the general health dimension of the Short Form Health Survey (SF-36). The secondary objectives were to assess other dimensional SF-36 scores, the impact of weight on the physical and psychosocial aspects of quality of life (IWQOL-Lite), and the burden of obesity-specific weight symptoms (WRSM). RESULTS: 73 patients were enrolled and reported patient reported outcome measures, with 71 patients (55% females) allocated to either MICT (n = 34) or HIIT/MICT (n = 37). In the intention-to-treat analysis, general health scores increased between baseline and 24-week follow-up in both the HIIT/MICT group and the MICT group, with a mean change of 13 (95% CI 6-21) points and 11 (95% CI 5-17) points, respectively, with no difference between the groups. The effect sizes of these changes were moderate. The vitality and social functioning scores of SF-36, and the physical function and self-esteem scores of IWQOL-Lite increased moderately in both groups, with no difference between groups. The tiredness, back pain, and physical stamina scores based on WRSM showed moderate to strong changes in both the groups. CONCLUSIONS: Patients who had completed a combined HIIT/MICT program did not experience larger improvements in general health compared with those completing a clean 24-week MICT program. Exercise may confer general health benefits independent of intensity. TRIALS REGISTRATION: Regional Committees for Medical and Health Research Ethics south east, Norway, October 23, 2013 (identifier: 2013/1849) and ClinicalTrials.gov December 8, 2014 (identifier: NCT02311738).

Correlations between 4ß-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.

PURPOSE: Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4ß-hydroxycholesterol (4ßOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4ßOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. METHODS: The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4ßOHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. RESULTS: 4ßOHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (ρ = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (ρ = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (ρ = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (ρ = 0.15, p = 0.53). 4ßOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ = - 0.23, p = 0.027) and apparent oral clearance (ρ = 0.28, p = 0.008), but not with systemic clearance (ρ = - 0.03, p = 0.81). CONCLUSION: These findings suggest that 4ßOHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4ßOHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs. TRIAL REGISTRATION: Clinical. TRIALS: gov identifier: NCT02386917.

Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids.

BACKGROUND: Limited evidence suggests that surgical and non-surgical obesity treatment differentially influence plasma Lipoprotein (a) [Lp(a)] levels. Further, a novel association between plasma arachidonic acid and Lp(a) has recently been shown, suggesting that fatty acids are a possible target to influence Lp(a). Here, the effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) were compared, and it was examined whether the effects were mediated by changes in plasma fatty acid (FA) levels. METHODS: The study includes two independent trials of patients with overweight or obesity. Trial 1: Two-armed intervention study including 82 patients who underwent a 7-week low energy diet (LED), followed by Roux-en-Y gastric bypass and 52-week follow-up (surgery-group), and 77 patients who underwent a 59-week energy restricted diet- and exercise-program (lifestyle-group). Trial 2: A clinical study including 134 patients who underwent a 20-week very-LED/LED (lifestyle-cohort). RESULTS: In the surgery-group, Lp(a) levels [median (interquartile range)] tended to increase in the pre-surgical LED-phase [17(7-68)-21(7-81)nmol/L, P = 0.05], but decreased by 48% after surgery [21(7-81)-11(7-56)nmol/L, P < 0.001]. In the lifestyle-group and lifestyle-cohort, Lp(a) increased by 36%[14(7-77)-19(7-94)nmol/L, P < 0.001] and 14%[50(14-160)-57(19-208)nmol/L, P < 0.001], respectively. Changes in Lp(a) were independent of weight loss. Plasma levels of total saturated FAs remained unchanged after surgery, but decreased after lifestyle interventions. Arachidonic acid and total n-3 FAs decreased after surgery, but increased after lifestyle interventions. Plasma FAs did not mediate the effects on Lp(a). CONCLUSION: Bariatric surgery reduced, whereas lifestyle interventions increased plasma Lp(a), independent of weight loss. The interventions differentially influenced changes in plasma FAs, but these changes did not mediate changes in Lp(a). TRIAL REGISTRATION: Trial 1: Clinicaltrials.gov NCT00626964. Trial 2: Netherlands Trial Register NL2140 (NTR2264).

A Comparative Analysis of Cytochrome P450 Activities in Paired Liver and Small Intestinal Samples from Patients with Obesity.

The liver and small intestine restrict oral bioavailability of drugs and constitute the main sites of pharmacokinetic drug-drug interactions. Hence, detailed data on hepatic and intestinal activities of drug metabolizing enzymes is important for modeling drug disposition and optimizing pharmacotherapy in different patient populations. The aim of this study was to determine the activities of seven cytochrome P450 (P450) enzymes in paired liver and small intestinal samples from patients with obesity. Biopsies were obtained from 20 patients who underwent Roux-en-Y gastric bypass surgery following a 3-week low-energy diet. Individual hepatic and intestinal microsomes were prepared and specific probe substrates in combined incubations were used for determination of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A activities. The activities of CYP2C8, CYP2C9, CYP2D6, and CYP3A were quantified in both human liver microsomes (HLM) and human intestinal microsomes (HIM), while the activities of CYP1A2, CYP2B6, and CYP2C19 were only quantifiable in HLM. Considerable interindividual variability was present in both HLM (9- to 23-fold) and HIM (5- to 55-fold). The median metabolic HLM/HIM ratios varied from 1.5 for CYP3A to 252 for CYP2C8. The activities of CYP2C9 in paired HLM and HIM were positively correlated (r = 0.74, P < 0.001), while no interorgan correlations were found for activities of CYP2C8, CYP2D6, and CYP3A (P > 0.05). Small intestinal CYP3A activities were higher in females compared with males (P < 0.05). Hepatic CYP2B6 activity correlated negatively with body mass index (r = -0.72, P < 0.001). These data may be useful for further in vitro-in vivo predictions of drug disposition in patients with obesity. SIGNIFICANCE STATEMENT: Hepatic and intestinal drug metabolism is the key determinant of oral drug bioavailability. In this study, paired liver and jejunum samples were obtained from 20 patients with obesity undergoing gastric bypass surgery following a 3-week low-energy diet. We determined the hepatic and small intestinal activities of clinically important P450 enzymes and provide detailed enzyme kinetic data relevant for predicting in vivo disposition of P450 substrates in this patient population.

Identifying Persuasive Design Principles and Behavior Change Techniques Supporting End User Values and Needs in eHealth Interventions for Long-Term Weight Loss Maintenance: Qualitative Study.

BACKGROUND: An increasing number of eHealth interventions aim to support healthy behaviors that facilitate weight loss. However, there is limited evidence of the effectiveness of the interventions and little focus on weight loss maintenance. Knowledge about end user values and needs is essential to create meaningful and effective eHealth interventions, and to identify persuasive system design (PSD) principles and behavior change techniques (BCTs) that may contribute to the behavior change required for successful long-term weight loss maintenance. OBJECTIVE: This study aimed to provide insight into the design of eHealth interventions supporting behavior change for long-term weight maintenance. The study sought to identify the values and needs of people with obesity aiming to maintain weight after weight loss, and to identify PSD principles, BCTs, and design requirements that potentially enable an eHealth intervention to meet end user values and needs. METHODS: This study presents the concept of integrating PSD principles and BCTs into the design process of eHealth interventions to meet user values and needs. In this study, individual interviews and focus groups were conducted with people with obesity (n=23) and other key stakeholders (n=27) to explore end user values and needs related to weight loss maintenance. Design thinking methods were applied during the focus group sessions to identify design elements and to explore how eHealth solutions can support the needs to achieve sustainable weight loss maintenance. The PSD model and behavior change taxonomy by Michie were used to identify PSD principles and BCT clusters to meet end user values and needs. RESULTS: A total of 8 key end user values were identified, reflecting user needs for weight loss maintenance support: self-management, personalized care, autonomy, feel supported, positive self-image, motivation, happiness, and health. Goals and planning, feedback and monitoring, repetition and substitution, shaping knowledge, social support, identity, and self-belief were some of the BCT clusters identified to address these concepts, together with PSD principles such as personalization, tailoring, self-monitoring, praise, and suggestions. CONCLUSIONS: The process of translating end user values and needs into design elements or features of eHealth technologies is an important part of the design process. To our knowledge, this is the first study to explore how PSD principles and BCTs can be integrated when designing eHealth self-management interventions for long-term weight loss maintenance. End users and other key stakeholders highlighted important factors to be considered in the design of eHealth interventions supporting sustained behavior change. The PSD principles and BCTs identified provide insights and suggestions about design elements and features to include for supporting weight loss maintenance. The findings indicate that a combination of BCTs and PSD principles may be needed in evidence-based eHealth interventions to stimulate motivation and adherence to support healthy behaviors and sustained weight loss maintenance. TRIAL REGISTRATION: ClinicalTrials.gov NCT04537988; https://clinicaltrials.gov/ct2/show/NCT04537988.

Loss of smell or taste as the only symptom of COVID-19. / Covid-19 med nedsatt lukte- og smakssans som eneste symptom.

BACKGROUND: Olfactory and taste disorders (OTDs) have recently been reported among patients with COVID-19, and it has been hypothesised that oral and nasal tissues may contain host cells of SARS-CoV-2. We report on two cases (spouses) with SARS-CoV-2 infection with self-reported OTDs, but otherwise no typical respiratory symptoms of COVID-19. CASE PRESENTATION: A man in his nineties (index patient) had respiratory symptoms and dysgeusia, and was diagnosed with COVID-19. His daughter-in-law and son had no respiratory COVID-19 symptoms. However, they experienced complete loss of smell and taste, respectively, 7 and 10 days after their first close contact with the index patient. Both tested positive for SARS-CoV-2 RNA. INTERPRETATION: Our case histories support recent reports hypothesising that anosmia and ageusia may be the only symptoms of SARS-CoV-2 infection, and that SARS-CoV-2 may infect oral and nasal tissues. Together, these findings may inform future research, diagnosis, prevention and treatment of COVID-19.

Patient complaints following bariatric surgery 2012-18. / Pasientklager etter vektreduserende kirurgi 2012­18.

BACKGROUND: We examined complaints submitted to the Norwegian System of Patient Injury Compensation (NPE) following bariatric surgery, including the background for the complaint, the proportion of patients whose complaints were upheld, and the characteristics of complaints that were upheld. MATERIAL AND METHOD: All complaints relating to bariatric surgery performed in the period 2012-18 were reviewed and categorised according to symptoms, findings and events relevant to the outcome of the complaint. Anonymous summaries from the experts' statements were reviewed and categorised according to year of decision, gender, age, basis for compensation or rejection, and whether the intervention was carried out in the public or private health service. RESULTS: Forty-four (26 %) of a total of 171 applications for patient injury compensation were upheld. These applications represented 25 patients who had surgery in the public health service (19 % upheld) and 19 patients who were operated on in the private health service (51 % upheld). The single most common reason for a complaint being upheld (n = 18) was lack of indication for bariatric surgery. INTERPRETATION: More post-bariatric surgery complaints were upheld for lack of indication than for surgical errors. Proper patient selection, good preoperative preparation, good information and shared decision-making are important factors for achieving the best possible bariatric surgery outcome. An interdisciplinary team that monitors patients over time can help ensure the quality of the entire treatment chain.

Laparoscopic gastric bypass versus lifestyle intervention for adolescents with morbid obesity. / Laparoskopisk gastrisk bypassoperasjon versus livsstilsbehandling av unge med sykelig overvekt.

BACKGROUND: There is limited evidence for the effectiveness of bariatric surgery in adolescents, and the associated complications. The main objective of the 4XL study was to clarify whether laparoscopic Roux-en-Y gastric bypass (LGBP) combined with lifestyle intervention is a safe and effective treatment method. MATERIAL AND METHOD: Data were retrieved from an ongoing non-randomised intervention study of adolescents with morbid obesity that is comparing the effects of gastric bypass combined with lifestyle intervention versus lifestyle intervention alone. RESULTS: Altogether 39 patients (64 % girls) treated with a gastric bypass, and 96 patients (57 % girls) treated with lifestyle intervention were examined prior to the start of treatment and one year later. The average age at inclusion (SD) was 16.7 (1.0) years vs. 15.6 (1.3) years, and average BMI was 45.6 (4.4) vs. 43.3 (4.1) kg/m2 in the two groups. Average (95 % CI) percentage weight loss was 30 % (27 %-33 %) after surgery versus weight gain of 1 % (-1 % to 3 %) in the control group. The difference between the groups was 31 % (95 % CI 27 %-34 %, p<0.001). Cardiometabolic risk factors improved only after surgery. After gastric bypass, two early (<6 weeks) minor complications were recorded. One year after surgery, 4 (10 %), 8 (21 %) and 4 (10 %) of patients had anaemia, iron deficiency or low vitamin B12 levels respectively, and 20 of 33 patients (61 %) had low two-hour blood glucose (<2.8 mmol/l) after oral glucose tolerance testing. INTERPRETATION: The results support previous studies showing that gastric bypass is associated with significant weight loss in adolescent patients with morbid obesity. The 4XL study is currently too small and the follow-up time too short to allow the risk of long-term complications to be assessed.

Lifestyle intervention for children and adolescents with severe obesity - results after one year. / Livsstilsbehandling av barn og ungdom med alvorlig fedme ­ resultater etter ett år.

BACKGROUND: Lifestyle interventions for children and adolescents with severe obesity show moderate short-term effects on weight reduction internationally. We evaluated treatment results at two Norwegian specialist outpatient clinics. MATERIAL AND METHOD: We performed a retrospective analysis of data from children and adolescents between 3 and 18 years of age collected in 2012-2016. Children and adolescents with severe obesity who attended their one-year follow-up were included. We included in the analyses the following body weight measures: percentage overweight as defined by the International Obesity Task Force cut-off (% IOTF-25); BMI standard deviation score; waist circumference standard deviation score; and body fat percentage at the start of treatment and at one-year follow-up. RESULTS: Of 568 children and adolescents who started treatment, 416 (73 %) attended the one-year check-up. A total of 271 (65 %) patients achieved a reduction in %IOTF-25, while 228 patients (55 %) reduced their BMI standard deviation score. There was a statistically significant mean reduction of all four registered body weight measurements. Altogether 54 of 325 children (17 %) changed category from severe obesity to obesity, 8 (2 %) went from severe obesity to overweight, and 8 of 91 children (9 %) changed category from obesity to overweight or normal weight. The proportion of participants with a reduction of more than 5 % in %IOTF-25 was 43 % (177/416), and a reduction in BMI standard deviation score of more than 0.25 was observed in 23 % (95/416) of participants. Girls responded on average more poorly to the intervention than boys. There was no clinically significant difference in results between the treatment centres. INTERPRETATION: After one year of treatment of children and adolescents with severe obesity in two specialist healthcare centres, we found a moderate mean reduction in weight, waist circumference and body fat percentage, but with large interindividual variation.

Associations between cardiorespiratory fitness and weight loss in patients with severe obesity undergoing an intensive lifestyle intervention program: retrospective cohort study.

BACKGROUND: To assess the association between cardiorespiratory fitness (CRF) and weight changes in treatment seeking patients with severe obesity who underwent a 1-year intensive lifestyle intervention (ILI) program. METHODS: Retrospective cohort study conducted at a tertiary care outpatient rehabilitation center from November 1, 2013 through January 1, 2017. CRF was measured as maximal oxygen consumption during a maximal oxygen uptake (VO2max) test on a treadmill or bicycle at baseline and after 3 months. RESULTS: A total of 180 patients had a baseline mean (SD) BMI 41.1 (4.8) kg/m2 and CRF of 79.4 (14.9) mL·kg-0.75·min- 1. Patients with a baseline CRF above median achieved a greater 3-month and 1-year weight loss compared with patients with CRF below median; mean (95% CI) 2.5 kg (1.3, 3.8) and 4.0 kg (0.8, 7.2), respectively. In addition, patients with 3-month changes of CRF above median had 4.0 kg (0.9, 7.1) greater weight loss at 1-year follow-up than those below median. CONCLUSIONS: Among patients with severe obesity who underwent a 1-year ILI program, higher baseline CRF was associated with significantly larger weight loss after 3 months and 1 year. In addition, those with higher initial 3-month CRF changes had greater weight loss at 1 year. TRIAL REGISTRATION: Retrospectively registered in Regional Committees for Medical and Health Research Ethics (REC) south east September 22, 2016 (2016/1414) and clinicaltials.gov August 13, 2018 (identifier: NCT03593798 ).

Cardiometabolic risk factors differ among adolescents with obesity in three European countries - a cross-sectional study.

AIM: We aimed to compare modifiable cardiometabolic risk factors among treatment-seeking adolescents with obesity in Italy, Germany and Norway. METHODS: This retrospective, registry-based, cross-sectional cohort study included 2,327 (59% girls) 12-18 year-old adolescents with obesity from three tertiary care outpatient clinics in Europe, between 1999 and 2015. The prevalence of cardiometabolic risk factors was compared between clinics, and multivariate logistic regression models including gender, age, waist circumference and body mass index were used to assess the associations between population and cardiometabolic risk. RESULTS: In total, 1,396 adolescents (60% girls) from Italy, 654 (58% girls) from Germany and 277 (51% girls) from Norway were included. The mean ± SD age was 15.2 ± 1.6 years, body mass index 38.8 ± 6.5 kg/m2 and body mass index standard deviation score 3.21 ± 0.43. The prevalence of elevated nonhigh-density lipoprotein-cholesterol in Norway, Germany and Italy was 60%, 54% and 45%, while the prevalence of high systolic or diastolic blood pressure (≥130 or ≥85 mmHg) were 15%, 46% and 66%, respectively. CONCLUSION: Cardiometabolic risk factors among treatment-seeking adolescents with obesity from Italy, Germany and Norway differed across the populations in this study, which might imply that preventive clinical work should reflect such differences.

Monitoring children and adolescents with severe obesity: body mass index (BMI), BMI z-score or percentage above the International Obesity Task Force overweight cut-off?

AIM: Body mass index (BMI) metrics are widely used as a proxy for adiposity in children with severe obesity. The BMI expressed as the percentage of a cut-off percentile for overweight or obesity has been proposed as a better alternative than BMI z-scores when monitoring children and adolescents with severe obesity. METHODS: Annual changes in BMI, BMI z-score and the percentage above the International Obesity Task Force overweight cut-off (%IOTF-25) were compared with dual-energy X-ray absorptiometry (DXA) derived body fat (%BF-DXA) in 59 children and adolescents with severe obesity. RESULTS: The change in %BF-DXA was correlated with the change in %IOTF-25 (r = 0.68) and BMI (r = 0.70), and somewhat less with the BMI z-score (r = 0.57). Cohen's Kappa statistic to detect an increase or decrease in %BF-DXA was fair for %IOTF-25 (κ = 0.25; p = 0.04) and BMI (κ = 0.33; p = 0.01), but not for the BMI z-score (κ = 0.08; p = 0.5). The change in BMI was positively biased due to a natural increase with age. CONCLUSION: Changes in the BMI metrics included in the study are associated differently with changes in %BF-DXA. The BMI z-score is widely used to monitor changes in adiposity in children and adolescents with severe obesity, but the %IOTF-25 might be a better alternative.