Overall and cause-specific mortality in anorexia nervosa; impact of psychiatric comorbidity and sex in a 40-year follow-up study.

OBJECTIVE: This study investigates the overall and cause-specific mortality in males and females with anorexia nervosa (AN) from 1977 to 2018, focusing on the impact of psychiatric comorbidity on mortality risk, a less explored aspect despite a high prevalence in patients with AN. METHOD: We conducted a nationwide population-based cohort study in Denmark including all patients with AN (n = 14,774) with a median follow-up time of 9.1 years and a 1:10 age- and sex-matched general population comparison cohort. Using Cox proportional hazard model, we calculated adjusted hazard ratios (aHR) for death stratified by psychiatric comorbidity, sex, and age at AN onset and evaluated the causes of death using Fine and Gray sub-distribution hazard ratios (SHR). RESULTS: In patients with AN, the weighted average aHR for all-cause mortality was 4.5 [95% CI 4.1-4.9] with up to 40 years follow-up. Psychiatric comorbidity was present in 47% of patients with AN at index date, which was associated with a 1.9-fold increase in 10-year mortality compared with patients without comorbidity and a notably four-fold increase, when diagnosed at age 6-25 years. The mortality risk was similar according to sex. 13.9% of all deaths in patients with AN were due to suicide (SHR 10.7 [8.1-14.2]). The risk of dying of natural causes was increased with a SHR of 3.8 [95% CI 3.4-4.2]. DISCUSSION: The increased mortality risk in both males and females with AN and psychiatric comorbidity, particularly when diagnosed at young age, underscores the need for comprehensive treatment addressing both AN and coexisting psychiatric conditions. PUBLIC SIGNIFICANCE: The mortality in patients with anorexia nervosa (AN) is high and we show in our study that the mortality is doubled in the presence of psychiatric comorbidity particularly the first 10 years after diagnosis seen in both sexes and with suicide as a major cause of death. These findings stress the importance of detection and treatment of psychiatric comorbidities alongside the eating disorder to prevent fatal outcome.

Perceptions, behaviours and potential barriers to effective obesity care. Results from the ACTION-DK study.

AIM: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark. METHODS: The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2 ) based on self-reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO. RESULTS: Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow-up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion. CONCLUSIONS: Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow-up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs.

Rate of Acute Hospital Admissions Before and After Roux-en-Y Gastric Bypass Surgery: A Population-based Cohort Study.

OBJECTIVE: To examine rates of acute inpatient hospital admissions patients undergoing Roux-en-Y gastric bypass (RYGB) surgery and a matched population-based comparison cohort. SUMMARY BACKGROUND DATA: Little is known about the admission rates before and after RYGB. METHODS: Nationwide population-based cohort study, including all 9985 patients undergoing RYGB in Denmark during 2006 to 2010, and 247,375 matched general population comparisons. We calculated cumulative incidence of surgical complications after RYGB and incidence rate ratios (RRs) of hospital admission in RYGB patients versus comparisons before and after RYGB. RESULTS: Admissions for surgical complications occurred in 3.3% (n = 328) of RYGB patients <30 days after surgery and in 23.9% (n = 2367) during entire follow-up (median 4.2 yrs). Fifteen percent (n = 1486) were admitted with abdominal pain, 5.2% (n = 518) with intestinal obstruction during follow-up. Overall admission rates in RYGB patients versus comparisons were 11.5 versus 5.9 per 100 person-years before RYGB [RR = 1.95 (95% confidence interval (CI): 1.89-2.01)], increasing to 24.9 versus 7.1 per 100 person-years after RYGB [RR = 3.38 (95% CI; 3.30, 3.47)]. RRs of cardiovascular and chronic pulmonary disease admissions decreased considerably. RRs increased for alcohol abuse [0.59 (95% CI; 0.39-0.88) to 2.17 (95% CI; 1.72-2.72)], self-harm (suicide attempts, medication overuse) [1.72 (95% CI; 1.32-2.25) to 3.61 (95% CI; 2.88-4.52)], anemia [0.84 (95% CI; 0.39-1.78) to 17.92 (95% CI; 14.94-21.48)], and osteoporosis [1.19 (95% CI; 0.93-1.53) to 1.65 (95% CI; 1.35-2.02)]. CONCLUSIONS: Short-term surgical complications occurred in 3% and long-term complications in one-fourth of RYGB patients. Compared with the general population, the RR for any inpatient admission increased after RYGB.

Changes in Prescription Drug Use After Gastric Bypass Surgery: A Nationwide Cohort Study.

OBJECTIVES: To evaluate changes over time in drug use among patients undergoing Roux-en-Y gastric bypass (RYGB) surgery and a matched population-based comparison cohort. BACKGROUND: A little is known about the prescription drug use before and after RYGB surgery. METHODS: Nationwide population-based cohort study included 9908 patients undergoing RYGB in Denmark during 2006 to 2010 and 99,080 matched general population members. We calculated prevalence ratios (PRs) comparing prescription drug use 36 months after RYGB/index date with use 6 months before this date (baseline). RESULTS: At baseline, more RYGB patients (median 40 years, 22% males) used a prescription drug (81.5% vs 49.1%). After 3 years, the use had decreased slightly among RYGB patients [PR = 0.93; 95% confidence interval (CI) = (0.91, 0.94)], but increased in the comparison cohort (PR = 1.05; 95% CI = 1.04-1.06). In the RYGB cohort, large, sustained decreases occurred for treatment of metabolic syndrome-related conditions, such as any glucose-lowering drug (PR = 0.28; 95% CI = 0.25-0.31) and lipid-modifying drugs PR = 0.50; 95% CI = 0.46-0.55). Use of inhalants for obstructive airway diseases (PR = 0.79; 95% CI = 0.74-0.85) also decreased. Use of neuropsychiatric drugs was two-fold higher at baseline in the RYGB cohort (22.8% vs 10.9%) and increased further after RYGB-that is, antidepressants (PR = 1.13; 95% CI = 1.07-1.19), antipsychotics (PR = 1.39; 95% CI = 1.21-1.60), and potential treatment of neuropathy (PR = 1.39; 95% CI = 1.28-1.51). CONCLUSIONS: Three years after RYGB surgery, we found large reductions in the use of treatment of metabolic syndrome-related conditions, inhalants for obstructive airway diseases and glucocorticoid use. In contrast, frequent use of neuropsychiatric drugs further increased after RYGB.

Review of impacts of using body mass index as a screening tool in school children: A scoping review.

Body mass index (BMI) is used to screen for under- or overweight. However, it is unknown whether BMI-screening in school children reduces the incidence of overweight and obesity. We aimed to summarise the knowledge on positive and negative consequences on BMI and weight-related perceptions and behaviours of BMI-screening followed by an intervention to prevent and/or address obesity. We performed a systematic literature search, April 2023, using the PubMed, ScienceDirect and Google Scholar databases. We included randomised controlled trials and observational studies, including children aged 6 to 18 years and examining BMI-screening in a school setting. The primary outcome measures were BMI and weight status. Secondary outcome measures were weight-related perceptions and behaviours. Three studies met the inclusion criteria; two randomised controlled trials and one observational study. All studies used BMI-screening followed by sending report cards to the parents. None of the studies found a change in BMI z-scores in school children. Screening could cause transitory body-dissatisfaction and increase peer weight talk, yet potentially reduce problematic weight behaviours like skipping meals or excessive dieting. Reporting BMI to parents may influence their perception of their children's weight status, but does not change behaviour. The sparse evidence available suggested that BMI screening followed by sending report cards to parents does not change BMI z-scores among children in primary, middle and high school. Studies using appropriate evidence-based weight management interventions as a follow-up are lacking. Such studies may improve future prevention, detection and treatment of weight-related issues.

Risk of cardiovascular disease after hospital-diagnosed overweight or obesity.

Objective: The aim was to examine the association between hospital-diagnosed overweight/obesity and incident CVD according to the time period of the overweight/obesity diagnosis. Design: This is a cohort study. Methods: From Danish national health registries, we identified all residents with a first-time hospital-based overweight/obesity diagnosis code, 1977-2018 (n = 195,221), and an age and sex-matched general population comparison cohort (n = 1,952,210). We computed adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression. We adjusted for comorbidities and educational level and applied 10 years of follow-up. Results: The overall incidence rate was 10.1 (95% CI 10.0-10.1) per 1000 person-years for the comparison cohort and 25.1 (95% CI 24.8-25.4) per 1000 person-years for the overweight/obesity cohort, corresponding to an aHR of 2.5 (95% CI 2.4-2.5). The aHR was elevated for all subtypes of CVD: heart failure: 3.9 (95% CI 3.7-4.1), bradyarrhythmia: 2.9 (95% CI 2.7-3.1), angina pectoris: 2.7 (95% CI 2.7-2.8), atrial fibrillation or flutter: 2.6 (95% CI 2.5-2.6), acute myocardial infarction: 2.4 (95% CI 2.3-2.4), revascularization procedure: 2.4 (95% CI 2.2-2.5), valvular heart disease: 1.7 (95% CI 1.6-1.8), ischemic stroke: 1.6 (95% CI 1.4-1.7), transient ischemic attack: 1.6 (95% CI 1.5-1.7), and cardiovascular death: 1.6 (95% CI 1.5-1.6). The 1-10-year aHR of any CVD associated with an overweight/obesity diagnosis decreased from 2.8 (95% CI 2.7-2.9) in 1977-1987 to 1.8 (95% CI 1.8-1.9) in 2008-2018. Conclusion: Patients with hospital-diagnosed overweight/obesity had high rates of ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and death, although the strength of the association decreased in recent years. Significance statement: Obesity is linked to metabolic abnormalities that predispose individuals to an increased risk of subtypes of CVD. In this population-based nationwide 40-year cohort study, we found that of 195,221 patients with an overweight/obesity diagnosis, more than 31,000 (15.9%) were admitted to hospital within 10 years because of CVD; corresponding to a 2.5-fold greater relative risk of any CVD associated with overweight/obesity than in the general population. We observed an increased risk for most CVD subtypes, including ischemic heart disease, heart failure, structural heart disease, arrhythmia, stroke, and cardiovascular death, although the strength of the association decreased in recent years. Our study emphasizes the importance of improved clinical handling of obesity and underscores the need to prevent associated complications to alleviate the burden of obesity.

Fracture Risk in Patients with Anorexia Nervosa Over a 40-Year Period.

Researchers have reported increased fracture risk in patients with anorexia nervosa (AN), but more knowledge on the long-term risk and the effects of age, male sex, and time-related changes is still needed. We examined the long-term (up to 40 years) fracture risk among patients with AN compared to a matched comparison cohort from the general population. We utilized data from the Danish Health Care Registers to identify 14,414 patients with AN (13,474 females and 940 males) diagnosed between 1977 and 2018, with a median age of 18.6 years and median follow-up time of 9.65 years. We calculated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox regression analysis for overall and site-specific fracture risks. The overall aHR of any fracture was 1.46 [95% CI: 1.36 to 1.48], with an aHR of 1.50 [95% CI: 1.43 to 1.57] for females and 0.95 [95% CI: 0.82 to 1.1] for males. For specific fractures we found an association with femur fractures both in females 4.06 [95% CI: 3.39 to 4.46] and in males 2.79 [95% CI: 1.45 to 2.37] and for fractures of the spine (females 2.38 [95% CI: 2.00 to 2.84], males 2.31 [95% CI: 1.20 to 4.42]). The aHR of any fracture decreased from 1.66 [95% CI: 1.52 to 1.81] in the period from 1977 to 1997 to 1.40 [95% CI: 1.33 to 1.40] from 1998 to 2018. In conclusion, we found that AN was associated with a 46% increased risk of any fracture up to 40 years after diagnosis. We found no overall increased risk in males, but in both sexes we found a particularly high site-specific fracture risk in the spine and femur. Fracture risk decreased in recent decades, indicating that more patients with AN have been diagnosed with presumably less severe disease and that the earlier detection and intervention of AN in recent years may translate into a lower facture risk. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The impact of age and obesity on outcomes among patients hospitalized with COVID-19 in Denmark: A nationwide cohort study.

Purpose: Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID-19). Age may impact the association between body weight and severity of COVID-19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19 in the initial wave of the pandemic. Patients and methods: Based on data from the nationwide, clinical database: COVID-DK, risks of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality were compared among patients with and without obesity. Interaction with age was examined and we used Inverse Probability of Treatment Weighting regression for confounder adjustment. Results: Among 524 patients, 142 (27%) were admitted to the ICU, 112 (21%) required IMV, and 109 (21%) died. Compared to COVID-19 patients without obesity, patients with obesity displayed a non-significant increased risk of ICU admission (Relative Risk [RR] 1.19, 95% Confidence Interval [CI] 0.88; 1.60), IMV (RR 1.23, CI 0.86; 1.75) and mortality (RR 1.21, CI 0.84; 1.75). COVID-19 patients with obesity, <60 years had highly increased risk of ICU admission (RR 1.92, CI 1.14; 3.24) and IMV (RR 1.95, CI 1.09; 3.49). Conclusions: In hospitalized COVID-19 patients, obesity conferred an approximately 20% increased risk for ICU admission, IMV, and death, although these relationships did not reach statistical significance. COVID-19 patients with obesity and <60 years had an almost doubled risk of ICU admission and IMV.

Epidemiological aspects of obesity and the metabolic syndrome.

The prevalence of obesity increases rapidly, in all ages and in all social classes. Epidemiological studies have documented that obesity have large long-term consequences, even in children, including development of metabolic syndrome and other obesity-associated comorbidities (i.e. diabetes mellitus type 2, cancer and cardiovascular diseases) which may largely impact the person's health, life expectancy, and quality of life. As summarised in this review, epidemiological studies add to our knowledge on comorbidities associated with obesity, the prognosis, and the prevalence of obesity over time.

Obesity stigma.

Obesity stigma refers to the pervasive sociocultural disapproval and prejudice against people with obesity which is associated with different negative traits. The stigmatisation of people with obesity manifests itself in different social areas, both privately and publicly, including in the health care system, often resulting in negative physical, social, and psychological consequences for people with obesity. Consequently, it is imperative that healthcare professionals seek to avoid and take action against this type of stigmatisation, e.g. when communicating about weight.

Mortality Among Danish Patients with a Hospital Diagnosis of Overweight or Obesity Over a 40-Year Period.

Purpose: Data on long-term mortality among patients with hospital-diagnosed overweight/obesity are limited. Thus, we aim to examine 40-year mortality among patients with hospital-diagnosed overweight/obesity, including cause-specific deaths, secular time trends, and potential effect modification by age, comorbidity, and socioeconomic factors. Patients and Methods: From national registries, we identified all Danes with a first hospital-based overweight/obesity diagnosis (N=331,185), 1979-2018, and constructed an age- and gender-matched general population comparison cohort (N=1,655,925). We computed mortality rates (MRs) per 1000 person-years and adjusted mortality rate ratios (aMRRs) with 95% confidence intervals (CIs), using Cox regression with adjustment for comorbidities and educational level. We performed stratified analyses on age, comorbidities, and socioeconomic factors. Results: The overall aMRR was 1.70 (95% CI: 1.68-1.72) for patients with overweight/obesity, mainly due to diabetes and other endocrine diseases (aMRR=2.68 [95% CI: 2.57-2.81]), cardiovascular (aMRR=1.95 [95% CI: 1.91-1.98]), and respiratory diseases (aMRR=1.83 [95% CI: 1.77-1.89]). The 1-10-year aMRR decreased from 2.06 (95% CI: 2.01-2.11) in 1979-1989 to 1.29 (95% CI: 1.26-1.32) in 2000-2009. We found effect modification by age: age 18 to <30 years: aMRR=2.44 (95% CI: 2.24-2.66) vs age ≥70 years: 1.35 (95% CI: 1.33-1.37); comorbidities: baseline comorbidities: aMRR=1.13 (95% CI: 1.10-1.15) vs no comorbidities: aMRR=1.83 (95% CI: 1.80-1.85); and educational level: high educational level: aMRR=1.81 (95% CI: 1.74-1.88) vs low educational level: aMRR=1.70 (95% CI: 1.67-1.72). Conclusion: Patients with overweight/obesity had a substantially increased long-term mortality, mainly due to diabetes, cardiovascular, and respiratory diseases. The excess mortality decreased during recent decades. Age, comorbidities, and socioeconomic factors modified the association.

Roux-en-Y gastric bypass versus sleeve gastrectomy: nationwide data from the Danish quality registry for treatment of severe obesity.

BACKGROUND: Bariatric surgery as treatment of obesity is increasing worldwide. No guidelines exist on which type of bariatric procedure to choose for the individual patient. OBJECTIVES: This study aims to compare Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) with respect to weight loss, complications, comorbidities, and quality of life. SETTING: A nationwide multi-center register-based cohort study. METHODS: We identified 16,053 patients treated by bariatric surgery from 2008 to 2021 (RYGB, n = 13,075; SG, n = 2978) from the Danish quality registry for treatment of severe obesity (DBSO). We calculated risk ratios (RRs) and prevalence ratios (PRs) comparing surgical complications, weight loss, and medical comorbidities by type of procedure up to 2 years after surgery. RESULTS: Patients treated with RYGB experienced a greater weight loss than patients treated by SG both after 1 year (PR, .53; 95% confidence interval [CI], .48-.58) and 2 years (PR, .46; 95% CI, .39-.54). Compared with RYGB, SG yielded a lower risk of readmission (RR, .71; 95% CI, .60-.85). Likewise, the risk of reoperation between 30 days and 1 year (RR, .40; 95% CI, .30-.53) and 1 and 5 years (RR, .15; 95% CI, .12-.20]) were lower following SG. At 1-year follow-up, 76% of patients treated with RYGB and 63% of patients treated with SG experienced diabetes remission. Ten percent and 61% of patients were lost to follow-up after 1 and 2 years, respectively. CONCLUSION: The DBSO is an important resource in studying treatment of severe obesity. Weight loss is slightly greater after RYGB than after SG, but RYGB is associated with more frequent readmissions and reoperations.

Validity of ICD-10 diagnoses of overweight and obesity in Danish hospitals.

PURPOSE: Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals. PATIENTS AND METHODS: We linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m2 as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m2. RESULTS: Of all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m2, yielding a PPV of 87.6% (95% CI: 87.2-88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3-94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6-86.6). The PPV increased with higher patient age: from 75.3% (95% CI: 73.8-76.9) in those aged 18-29 years to 94.7% (95% CI: 92.6-96.9) in patients aged 80 years and above. Completeness of obesity/overweight diagnosis coding among patients recorded with BMI ≥25 kg/m2 was only 10.9% (95% CI: 10.8-11.0). CONCLUSION: Our findings indicate a high validity of the ICD-10 code E66 for overweight/obesity when recorded; however, completeness of coding was low. Nonetheless, ICD-10 discharge codes may be a suitable source of data on overweight/obesity for epidemiological research.

Body Mass Index of 92,027 patients acutely admitted to general hospitals in Denmark: Associated clinical characteristics and 30-day mortality.

BACKGROUND: Data are sparse on the range of BMI among patients acutely admitted to general hospitals. We investigated BMI values and associated patient characteristics, reasons for hospital admission, and mortality in Denmark. METHODS: We identified all persons with an acute inpatient admission 2011-2014 in Central Denmark Region and assessed BMI measurements recorded in the Clinical Information System. We used cross-sectional and cohort analyses to examine the BMI distribution and its association with demographic characteristics, comorbidities, medication use, tobacco smoking, reasons for admission, and 30-day mortality. RESULTS: Among 92,027 acutely admitted patients (median age 62 years, 49% female) with a BMI measurement, 4% had a BMI (kg/m2) <18.5, 42% a BMI between 18.5 and 25, 34% a BMI between 25 and 30, and 20% a BMI ≥30. Compared with normal-weight patients, 30-day mortality was high among patients with BMI <18.5 (7.5% vs. 2.8%, age- and smoking-adjusted odds ratio (aOR) 2.4; 95% confidence interval (CI): 2.0-2.9, whereas patients with overweight (aOR 0.7; 95% CI: 0.6-0.8) and obesity class I (aOR 0.8; 95% CI: 0.6-0.9)). Compared with the total population, patients with BMI <18.5 were older (68 years median); more were female (73%); more had comorbidities (Charlson Comorbidity Index score >0 in 42% vs. 33% overall), more were current smokers (45% vs. 27% overall), and acute admissions due to respiratory diseases or femoral fractures were frequent. In contrast, patients with BMI ≥30 were relatively young (59 years median), fewer smoked (24%): type 2 diabetes, sleep disorders, cholelithiasis, and heart failure were frequent diagnoses. Prevalence of therapies for metabolic syndrome, pain, and psychiatric disorders increased with higher BMI, while patients with BMI <18.5 frequently used asthma medications, glucocorticoids, and antibiotics. CONCLUSION: In patients acutely admitted to general hospitals, reasons for hospital admission and associated clinical characteristics differ substantially according to BMI range. BMI <18.5 is a clinical predictor of high short-term mortality.

Overall and cause-specific mortality after Roux-en-Y gastric bypass surgery: A nationwide cohort study.

BACKGROUND: Few population-based studies provide data on mortality after bariatric surgery. We hypothesized that hypoglycemia could be an underdiagnosed cause of death. OBJECTIVES: To examine perioperative, all-cause, and cause-specific long-term mortality in Roux-en-Y gastric bypass (RYGB) patients versus population comparisons. SETTING: Danish nationwide population-based cohort study. METHODS: We included all 9895 patients who underwent RYGB during 2006-2010, and a 1:25 age- and gender-matched comparison cohort (n = 247,366) (0.3% lost to follow up). We compared mortality rates and computed mortality rate ratios (MRR) for all-cause and cause-specific mortality using Cox regression analysis. For deceased RYGB patients (n = 91), we conducted a detailed medical record audit. RESULTS: The perioperative (30-days) mortality after RYGB was .04% (4/9895). After 4.2 years, RYGB-related mortality (deaths due to intestinal obstruction/intra-abdominal leakage) was .15% (16/9895). All-cause mortality was very similar in the 2 cohorts (median age, 40.2 years; 21.7% men): RYGB cohort, .89% (n = 91); comparison cohort, .92% (n = 2204); MRR = 1.03 (95% confidence interval [CI], .84-1.27). Mortality due to suicide (2.78; 95% CI, 1.44-5.33), accidents (2.29; 95% CI, 1.16-4.54), gastrointestinal diseases (2.01; 95% CI, 1.06-3.84), and infectious diseases (1.75; 95% CI, .98-3.17) was higher in the RYGB cohort versus comparison groups, but mortality from cancer was lower (0.43; 95% CI, .27-.70). Our medical record audit indicated that 8% of deaths after RYGB (n = 7) were possibly hypoglycemia related. CONCLUSION: Perioperative mortality after RYGB is low in Denmark, and subsequent all-cause mortality is similar to that of matched comparisons. After RYGB, patients have substantially increased mortality due to external causes such as suicide, accidents, and possibly hypoglycemia.

Control of confounding in the analysis phase - an overview for clinicians.

In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and disadvantages of different methods, we emphasize the importance of the clinical input and of the interplay between clinicians and analysts to ensure a proper analysis.

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies.

[Many complications after Roux-en-Y gastric bypass surgery can be prevented and treated].

A wide range of complications may occur after Roux-en-Y gastric bypass (RYGB) surgery, including surgical, medical/nutritional, and psychiatric complications. Some of the nutritional complications such as anaemia, dumping and hypoglycaemia may present rather unspecific symptoms that may easily not be diagnosed as complications after RYGB. Focus on diagnosis and treatment of these complications is important.

Prevalence of Self-reported Symptoms After Gastric Bypass Surgery for Obesity.

IMPORTANCE: Population-based studies on the prevalence of symptoms after Roux-en-Y gastric bypass (RYGB) surgery are sparse. Knowledge about possible predictors of these symptoms is important for prevention. OBJECTIVES: To examine patients' overall well-being and the prevalence and predictors of medical, nutritional, and surgical symptoms after RYGB surgery, and their association with quality of life. DESIGN, SETTING, AND PARTICIPANTS: A survey was conducted from March 3 to July 31, 2014, among 2238 patients who underwent RYGB surgery between January 1, 2006, and December 31, 2011, in the Central Denmark Region. A comparison cohort of 89 individuals who were matched with patients according to sex and body mass index but who did not undergo RYGB surgery were surveyed as a point of reference. Data analysis was conducted from September 1, 2014, to June 25, 2015. MAIN OUTCOMES AND MEASURES: Prevalence and severity (based on contacts with health care system, ranging from no contact to hospitalization) of self-reported symptoms following RYGB surgery. Prevalence ratios (PRs) of symptoms associated with different predictors were computed. The association between number of symptoms and quality of life was investigated using the Spearman rank correlation coefficient. RESULTS: Of 2238 patients undergoing RYGB surgery, 1429 (63.7%) responded to the survey. Among these patients, 1266 (88.6%) reported 1 or more symptoms a median of 4.7 years after RYGB surgery. Mean age at the time of the survey was 47.1 years (range, 26.9-68.0 years), and 286 were men (20.0%). A total of 1219 of 1394 patients (87.4%) reported that their well-being was improved after vs before RYGB surgery, while 113 (8.1%) reported reduced well-being. Symptoms after RYGB surgery were reported by 1266 patients (88.6%); 966 patients (67.6%) had been in contact with the health care system about their symptoms vs 31 [34.8%] of those in the comparison group, and 416 (29.1%) had been hospitalized vs 6 [6.7%] of those in the comparison group. The symptoms most commonly leading to health care contact after RYGB surgery were abdominal pain (489 [34.2%]), fatigue (488 [34.1%]), and anemia (396 [27.7%]). The risk of symptoms was higher among women (crude PR, 1.23; 95% CI, 1.11-1.37), among patients younger than 35 years (PR, 1.24; 95% CI, 1.13-1.36), among smokers (PR, 1.11; 95% CI, 1.02-1.20), among unemployed persons (PR, 1.15; 95% CI, 1.06-1.24), and in those with surgical symptoms before RYGB surgery (PR, 1.34; 95% CI, 1.25-1.43). Quality of life was inversely associated with the number of symptoms (r = -0.30; P < .001). CONCLUSIONS AND RELEVANCE: Most patients reported improved well-being after RYGB surgery, but the prevalence of symptoms was high and nearly one-third of patients were hospitalized, 4- to 5-fold more than among the comparison group. Predictors of symptoms included young age, female sex, smoking, and experiencing symptoms before RYGB surgery. Development of weight loss procedures with fewer subsequent symptoms should be a high priority.

Prevalence, severity, and predictors of symptoms of dumping and hypoglycemia after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in pronounced weight loss in morbidly obese patients but may also cause adverse effects like early dumping and hypoglycemia. Prevalence data on these complications and their potential predictors are sparse. OBJECTIVE: To assess the prevalence and possible predictors of early dumping and hypoglycemia in a population-based cohort of RYGB patients. SETTING: University Hospital, Denmark. DESIGN: A questionnaire survey was performed in the Central Denmark Region including RYGB-operated patients (years 2006-2011, n = 2238) and a nonoperated comparison cohort (n = 89). The Dumping Rating Scale and the Edinburgh Hypoglycemia Scoring System, together with demographic and clinical characteristics, were used, and possible predictors were examined by logistic regression. RESULTS: The response rate was 64% (1429/2238). In total, 9.4% (134/1429) and 6.6% (95/1429) experienced moderate or severe symptoms of early dumping and hypoglycemia, respectively, which were significantly higher than in the comparison cohort. Because 3.4% (95% CI: 2.5-4.4) of the RYGB group experienced both early dumping and hypoglycemia, the total prevalence of 1 or both conditions was 12.6 (95% CI 10.9-14.4). Possible predictors for both conditions were body mass index (BMI)<25 kg/m2 (odds ratio [OR] 1.70 (95% CI: 0.98-2.95) and OR 1.60 (95% CI: .83-3.06), respectively) compared with patients with BMI 25-30 kg/m2. Younger age seemed to increase the risk of both conditions (<35 yr: OR 1.75 (95% CI: 1.11-2.75) and OR .59 (95% CI: .93-2.72), respectively) compared with patients>45 years. CONCLUSION: Symptoms of early dumping and hypoglycemia were rather common with a prevalence of 1 or both conditions of 12.6% after RYGB. Predictors included younger age and a lower BMI.