Screening for pre-eclampsia with competing-risks model using placental growth factor measurement in blood samples collected before 11 weeks' gestation.

OBJECTIVES: To describe the distributional properties and assess the performance of placental growth factor (PlGF) measured in blood samples collected before 11 weeks' gestation in the prediction of pre-eclampsia (PE). METHODS: The study population consisted of pregnant women included in the Pre-eclampsia Screening in Denmark (PRESIDE) study with a PlGF measurement from the routine combined first-trimester screening (cFTS) blood sample collected at 8-14 weeks' gestation. PRESIDE was a prospective multicenter study investigating the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for PE in a Danish population. In the current study, serum concentration of PlGF in the cFTS blood samples was analyzed in batches between January and June 2021. RESULTS: A total of 8386 pregnant women were included. The incidence of PE was 0.7% at < 37 weeks' gestation and 3.0% at ≥ 37 weeks. In blood samples collected at 10 weeks' gestation, PlGF multiples of the median (MoM) were significantly lower in pregnancies with preterm PE < 37 weeks compared to unaffected pregnancies. However, PlGF MoM did not differ significantly between pregnancies with PE and unaffected pregnancies in samples collected before 10 weeks' gestation. CONCLUSIONS: The gestational-age range for PlGF sampling may be expanded from 11-14 to 10-14 weeks when assessing the risk for PE using the FMF first-trimester screening model. There is little evidence to support the use of PlGF in blood samples collected before 10 weeks' gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Mental disorder prevalence in chronic pain patients using opioid versus non-opioid analgesics: A registry-linkage study.

BACKGROUND: Chronic pain and mental disorders are leading causes of disability worldwide. Individuals with chronic pain are more likely to experience mental disorders compared to individuals without chronic pain, but large-scale estimates are lacking. We aimed to calculate overall prevalence of mental health diagnoses from primary and secondary care among individuals treated for chronic pain in 2019 and to compare prevalence among chronic pain patients receiving opioid versus non-opioid analgesics, according to age and gender. METHODS: It is a population-based cohort study. Linked data from nationwide health registers on dispensed drugs and diagnoses from primary (ICPC-2) and secondary (ICD-10) health care. Chronic pain patients were identified as all patients over 18 years of age filling at least one prescription of an analgesic reimbursed for non-malignant chronic pain in both 2018 and 2019 (N = 139,434, 69.3% women). RESULTS: Prevalence of any mental health diagnosis was 35.6% (95% confidence interval: 35.4%-35.9%) when sleep diagnoses were included and 29.0% (28.8%-29.3%) when excluded. The most prevalent diagnostic categories were sleep disorders (14% [13.8%-14.2%]), depressive and related disorders (10.1% [9.9%-10.2%]) and phobia and other anxiety disorders (5.7% [5.5%-5.8%]). Prevalence of most diagnostic categories was higher in the group using opioids compared to non-opioids. The group with the highest overall prevalence was young women (18-44 years) using opioids (50.1% [47.2%-53.0%]). CONCLUSIONS: Mental health diagnoses are common in chronic pain patients receiving analgesics, particularly among young individuals and opioid users. The combination of opioid use and high psychiatric comorbidity suggests that prescribers should attend to mental health in addition to somatic pain. SIGNIFICANCE: This large-scale study with nation-wide registry data supports previous findings of high psychiatric burden in chronic pain patients. Opioid users had significantly higher prevalence of mental health diagnoses, regardless of age and gender compared to users of non-opioid analgesics. Opioid users with chronic pain therefore stand out as a particularly vulnerable group and should be followed up closely by their physician to ensure they receive sufficient care for both their mental and somatic symptoms.

Risk factors for and consequences of difficult fetal extraction in emergency caesarean section. A retrospective registry-based cohort study.

INTRODUCTION: This study aimed to assess risk factors for difficult fetal extraction in emergency caesarean sections, focusing on top-up epidural anesthesia compared to spinal anesthesia. Additionally, this study addressed consequences of difficult fetal extraction on neonatal and maternal morbidity. MATERIAL AND METHODS: This retrospective registry-based cohort study included 2,332 of 2,892 emergency caesarean sections performed with local anesthesia during 2010-2017. Main outcomes were analyzed by crude and multiple adjusted logistic regression providing odds ratios. RESULTS: Difficult fetal extraction was found in 14.9% of emergency caesarean sections. Risk-factors for difficult fetal extraction included top-up epidural anesthesia (aOR:1.37[95 %CI 1.04-1.81]), high pre-pregnancy BMI (aOR:1.41[95 %CI 1.05-1.89]), deep fetal descent (ischial spine: aOR:2.53[95 %CI 1.89-3.39], pelvic floor: aOR:3.11[95 %CI 1.32-7.33]), and anterior placental position (aOR:1.37[95 %CI 1.06-1.77]). Difficult fetal extraction was associated with increased risk of low umbilical artery pH 7.00-7.09 (aOR:3.50[95 %CI 1.98-6.15]) pH ≤ 6.99 (aOR:4.20[95 %CI 1.61-10.91]), five-minute Apgar score ≤ 6 (aOR:3.41[95 %CI 1.49-7.83]) and maternal blood loss (501-1,000 ml: aOR:1.65[95 %CI 1.27-2.16], 1,001-1,500 ml: aOR:3.24[95 %CI 2.24-4.67], 1,501-2,000 ml: aOR:3.94[95 %CI 2.24-6.94] and ≥ 2001 ml: aOR:2.76[95 %CI 1.12-6.82]). CONCLUSION: This study identified four risk factors for difficult fetal extraction in emergency caesarean section: top-up epidural anesthesia, high maternal BMI, deep fetal descent and anterior placental position. Additionally, difficult fetal extraction was associated with poor neonatal and maternal outcomes.

Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prescription opioids among older adults: ten years of data across five countries.

BACKGROUND: Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on individual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009-2018. METHODS: We conducted cross-sectional measurements of opioid utilisation in 2009-2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day. RESULTS: From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries; an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation. CONCLUSIONS: The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009-2018. We found large cross-national differences despite similarities across the countries' cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.

Incidence of persistent postpartum opioid use by mode of delivery: a 2016 cohort study of Danish women.

BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365 days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.

Cardiovascular function in 8- to 9-year-old singletons born after ART with frozen and fresh embryo transfer.

STUDY QUESTION: Do 8- to 9-year-old singletons conceived after frozen embryo transfer (FET) or fresh embryo transfer (Fresh-ET) have increased arterial stiffness compared to naturally conceived (NC) children? SUMMARY ANSWER: The process of FET or Fresh-ET is not associated with altered cardiovascular function in 8- to 9-year-old singletons, including arterial stiffness, as compared to NC children. WHAT IS KNOWN ALREADY: ART has been suggested to influence cardiovascular risk factors (i.e. endothelial dysfunction, increased arterial blood pressure and insulin resistance). It is not known if ART procedures alter arterial stiffness in singletons. STUDY DESIGN, SIZE, DURATION: A cohort study was carried out, including 8- to 9-year-old singletons conceived after FET, Fresh-ET and NC children (50 children in each group). This study was conducted between November 2018 and August 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 150 singletons were identified through the Danish IVF Registry and the Medical Birth Registry. They underwent cardiac magnetic resonance imaging (CMR) and anthropometric measurements. Parental data were collected using questionnaires. NC children were matched by sex and birth year with FET/Fresh-ET children. Exclusion criteria were congenital heart disease, maternal gestational diabetes or maternal diabetes mellitus. Our primary outcome was arterial stiffness, which is assessed from noninvasive arterial blood pressure and aortic ascendens distensibility. The secondary outcome was the pulse wave velocity of total aorta and exploratory outcomes were left ventricular ejection fraction, mean arterial pressure, cardiac output and total peripheral resistance. Measurements and analyses were performed blinded to the child group. MAIN RESULTS AND THE ROLE OF CHANCE: Aortic ascendens distensibility of children conceived after FET and Fresh-ET did not differ from NC children (mean (SD): FET 11.1 (3.6) 10-3 mmHg-1, Fresh-ET 11.8 (3.0) 10-3 mmHg-1, NC 11.4 (2.8) 10-3 mmHg-1, P > 0.05). Multivariate linear regression was performed to adjust for potential confounders (i.e. child sex and age, maternal BMI at early pregnancy and maternal educational level). Data showed no statistically significant differences between study groups and aortic ascendens distensibility. However, the fully adjusted model showed a non-significant tendency of lowered aortic ascendens distensibility in children born after FET compared to Fresh-ET (ß estimate (95% CI): -0.99 10-3 mmHg-1 (-2.20; 0.21)) and NC children (ß estimate (95% CI): -0.77 10-3 mmHg-1 (-1.98; 0.44)). Lastly, secondary and exploratory outcomes did not differ between the groups. Primary and secondary outcomes showed good intra-rater reliability. LIMITATIONS, REASONS FOR CAUTION: This study is possibly limited by potential selection bias as the participation rate was higher in the ART compared to the NC group. Also, in some variables, the study groups differed slightly from the non-participant population. The non-participant population (n = 1770) included those who were excluded, not invited to CMR scan, or declined to participate in this study. WIDER IMPLICATIONS OF THE FINDINGS: Our findings indicate that children born after FET or Fresh-ET do not have altered cardiovascular function, including arterial stiffness. This is reassuring for the future use of ART. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Novo Nordisk Foundation (grant reference number: NNF19OC0054340) and The Research Foundation of Rigshospitalet. All authors declared no conflict of interests. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03719703.

The Mortality After Release from Incarceration Consortium (MARIC): Protocol for a multi-national, individual participant data meta-analysis.

INTRODUCTION: More than 30 million adults are released from incarceration globally each year. Many experience complex physical and mental health problems, and are at markedly increased risk of preventable mortality. Despite this, evidence regarding the global epidemiology of mortality following release from incarceration is insufficient to inform the development of targeted, evidence-based responses. Many previous studies have suffered from inadequate power and poor precision, and even large studies have limited capacity to disaggregate data by specific causes of death, sub-populations or time since release to answer questions of clinical and public health relevance. OBJECTIVES: To comprehensively document the incidence, timing, causes and risk factors for mortality in adults released from prison. METHODS: We created the Mortality After Release from Incarceration Consortium (MARIC), a multi-disciplinary collaboration representing 29 cohorts of adults who have experienced incarceration from 11 countries. Findings across cohorts will be analysed using a two-step, individual participant data meta-analysis methodology. RESULTS: The combined sample includes 1,337,993 individuals (89% male), with 75,795 deaths recorded over 9,191,393 person-years of follow-up. CONCLUSIONS: The consortium represents an important advancement in the field, bringing international attention to this problem. It will provide internationally relevant evidence to guide policymakers and clinicians in reducing preventable deaths in this marginalized population. KEY WORDS: Mortality; incarceration; prison; release; individual participant data meta-analysis; consortium; cohort.

Type 1 diabetes in children born after assisted reproductive technology: a register-based national cohort study.

STUDY QUESTION: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes? SUMMARY ANSWER: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer. WHAT IS KNOWN ALREADY?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies. STUDY DESIGN, SIZE, DURATION: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out. PARTICIPANTS/MATERIAL, SETTING, METHODS: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51). LIMITATIONS, REASONS FOR CAUTION: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population. WIDER IMPLICATIONS OF THE FINDINGS: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: ISRCTN 11780826.

Influence of physical and psychosocial working conditions for the risk of disability pension among healthy female eldercare workers: Prospective cohort.

Aim: To investigate the influence of physical and psychosocial working conditions on the risk of disability pension among eldercare workers. Methods: After responding to a questionnaire in 2005, 4699 healthy female eldercare workers - free from chronic musculoskeletal pain, depressive symptoms and long-term sickness absence - were followed for 11 years in the Danish Register for Evaluation of Marginalization. Time-to-event analyses estimated the hazard ratio (HR) for disability pension from physical exertion during work, emotional demands, influence at work, role conflicts, and quality of leadership. Analyses were mutually adjusted for these work environmental factors as well as for age, education, smoking, leisure physical activity and body mass index. Results: During follow-up, 7.6% received disability pension. Physical exertion and emotional demands were associated with risk of disability pension, and both interacted with age. In age-stratified analyses, older eldercare workers (mean age 53 years at baseline) with moderate and high physical exertion (reference: low) were at increased risk with HRs of 1.51, 95% CI [1.06-2.15] and 2.54, 95% CI [1.34-4.83], respectively. Younger eldercare workers (mean age 36 years at baseline) with moderate emotional demands (reference: low) were at decreased risk with an HR of 0.57, 95% CI [0.37-0.85]. Conclusions: While a higher level of physical exertion is a risk factor for disability pension among older female eldercare workers, a moderate level of emotional demands is associated with lower risk among the younger workers. The age of the worker may be an important factor when providing recommendations for promoting a long and healthy working life.

Two-week inhalation of budesonide increases muscle Na,K ATPase content but not endurance in response to terbutaline in men.

While chronic systemic administration of glucocorticoids increases muscle Na+ ,K+ ATPase content, such effect is unexplored after therapeutic inhalation. We investigated the effect of therapeutic inhalation of the glucocorticoid budesonide on Na+ ,K+ ATPase content of skeletal muscle in men. Ten healthy trained subjects, aged 23 ± 4 years (mean ± 95% CI), participated in the study. Before and after 2 weeks of daily inhalation of budesonide (1.6 mg/day), a biopsy was taken from the vastus lateralis muscle for measurement of Na+ ,K+ ATPase content and blood samples were drawn for determination of plasma budesonide, cortisol, and K+ . Subjects' performance during cycling to fatigue at 90% of incremental peak power output (iPPO) was measured in response to 4 mg inhaled terbutaline to maximally stimulate Na+ ,K+ ATPase activity. Plasma concentrations of budesonide rose to 5.0 ± 1.6 nM with the intervention, whereas no changes were observed in plasma cortisol. Muscle Na+ ,K+ ATPase content increased (P ≤ 0.01) by 46 ± 34 pmol/(g wet wt) (17% increase) with the intervention. Cycling performance at 90% of iPPO did not change (P = 0.21) with the intervention (203 vs 214 s) in response to terbutaline. The present observations show that therapeutic inhalation of glucocorticoids increases muscle Na+ ,K+ ATPase content, but does not enhance high-intensity cycling endurance in response to terbutaline.

Increased glucose-stimulated FGF21 response to oral glucose in obese nondiabetic subjects after Roux-en-Y gastric bypass.

OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. RESULTS: Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. CONCLUSIONS: In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass.

Effects of RYGB on energy expenditure, appetite and glycaemic control: a randomized controlled clinical trial.

OBJECTIVES: Increased energy expenditure (EE) has been proposed as an important mechanism for weight loss following Roux-en-Y gastric bypass (RYGB). However, this has never been investigated in a controlled setting independent of changes in energy balance. Similarly, only few studies have investigated the effect of RYGB on glycaemic control per se. Here, we investigated the effect of RYGB on EE, appetite, glycaemic control and specific signalling molecules compared with a control group in comparable negative energy balance. SUBJECTS/METHODS: Obese normal glucose-tolerant participants were randomized to receive RYGB after 8 (n=14) or 12 weeks (n=14). The protocol included a visit at week 0 and three visits (weeks 7, 11 and 78) where 24-h EE, appetite and blood parameters were assessed. Participants followed a low-calorie diet from weeks 0-11, with those operated at week 12 serving as a control group for those operated at week 8. RESULTS: Compared with controls, RYGB-operated participants had lower body composition-adjusted 24-h EE and basal EE 3 weeks postoperatively (both P<0.05) but EE parameters at week 78 were not different from preoperative values (week 7). Surgery changed the postprandial response of glucagon-like peptide-1 (GLP-1), peptide YY3-36 (PYY), ghrelin, cholecystokinin, fibroblast growth factor-19 and bile acids (all P<0.05). Particularly, increases in GLP-1, PYY and decreases in ghrelin were associated with decreased appetite. None of HOMA-IR (homeostasis model assessment-estimated insulin resistance), Matsuda index, the insulinogenic index, the disposition index and fasting hepatic insulin clearance were different between the groups, but RYGB operated had lower fasting glucose (P<0.05) and the postprandial glucose profile was shifted to the left (P<0.01). CONCLUSIONS: Our data do not support that EE is increased after RYGB. More likely, RYGB promotes weight loss by reducing appetite, partly mediated by changes in gastrointestinal hormone secretion. Furthermore, we found that the early changes in glycaemic control after RYGB is to a large extent mediated by caloric restriction.

Should physical activity recommendation depend on state of low back pain?

BACKGROUND: Leisure time physical activity is recommended for preventing long-term sickness absence (LTSA). Although low back pain (LBP) is a risk factor for sickness absence and physical activity is recommended for people with LBP, it is unknown if leisure time physical activity prevents LTSA among persons with different levels of LBP. METHODS: Prospective cohort study among 8655 Danish female healthcare workers responding to a questionnaire in 2004-2005 on leisure time physical activity and LBP, and subsequently followed for 1 year on periods with LTSA ∼2 consecutive weeks or more of sickness absence in a national register of social transfer payments (DREAM). Multi-adjusted Cox regression analysis was used to model risk estimates for LTSA associated with low, moderate, high and very high leisure time physical activity at baseline among healthcare workers with no LBP (0 days past 12 months, n = 2761), non-chronic LBP (1-30 days the past 12 months, n = 3942) and persistent LBP (>30 days the past 12 months, n = 1952). RESULTS: A strongly reduced risk for LTSA from high leisure time physical activity was found among healthcare workers with no LBP [hazard ratio (HR): 95% confidence interval (CI) 0.47:0.23-0.97 for low vs. very high activity] and non-chronic LBP (HR: 95%CI 0.43:0.23-0.84 of low vs. very high activity), but not among healthcare workers with persistent LBP (HR: 95%CI 1.15:0.55-2.44 of low vs. very high activity). CONCLUSIONS: Leisure time physical activity is a strong predictive factor on LTSA among female healthcare workers with no and non-chronic LBP, but not among those with more persistent LBP.

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass.

OBJECTIVE: To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). DESIGN: Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender. MATERIALS AND METHODS: Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. RESULTS: Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition. CONCLUSION: Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Does occupational lifting and carrying among female health care workers contribute to an escalation of pain-day frequency?

BACKGROUND: The aim of the study was to investigate if different frequencies, loads and trunk postures of occupational lifting and carrying increases the risk of sub-chronic (1-30 days last 12 months) low back pain (LBP) to become persistent (>30 days last 12 months) among female health care workers. METHODS: Female health care workers answered a questionnaire about occupational lifting or carrying frequency (rarely, occasionally and frequently), load (low: 1-7 kg, moderate: 8-30 kg and heavy: >30 kg) and trunk posture (upright or forward bent back), and days with LBP in 2005 and 2006. RESULTS: The odds ratio (OR) for developing persistent LBP in 2006 from these characteristics of occupational lifting and carrying was investigated with multi-adjusted logistic regressions among female health care workers with sub-chronic LBP (n = 2381) in 2005. Among health care workers with sub-chronic LBP, increased risk of persistent LBP was found from frequently lifting or carrying with forward bent back of moderate loads (OR: 1.63; 95% CI: 1.15-2.33) and heavy loads (OR: 1.56; 95% CI: 1.04-2.34). No increased risk for LBP to develop into a persistent condition was found for frequent lifting with upright back, frequent lifting or carrying of light loads, or occasionally lifting or carrying of any loads. CONCLUSIONS: Preventive initiatives for sub-chronic LBP to develop into a persistent condition ought to focus on reducing frequent lifting and carrying of moderate and heavy loads with forward bent back.

Increased somatic morbidity in the first year after leaving opioid maintenance treatment: results from a Norwegian cohort study.

BACKGROUND/AIMS: Some patients on opioid maintenance treatment (OMT) leave treatment temporarily or permanently. This study investigated whether patients interrupting their OMT differed from non-interrupters in sociodemographic and drug-use characteristics and examined acute/sub-acute somatic morbidity among the interrupters, prior to, during, and after OMT. METHODS: Cohort design. OBSERVATION PERIOD: 5 years prior to, up to first 5 years during, and up to 5 years after interruption of OMT. PARTICIPANTS: The sample (n = 200) comprised 51 OMT interrupters and 149 non-interrupters. Data on patient characteristics were obtained from interviews and OMT register information. Data on somatic morbidity were gathered from hospital records. MEASUREMENTS: Key patient characteristics among OMT interrupters and non-interrupters. Incidence rates of acute and sub-acute somatic disease incidents leading to hospital treatment (drug-related/non-drug-related/injuries) prior to/during/after OMT. RESULTS: Interrupters and non-interrupters did not differ in sociodemographic characteristics, while longer duration of amphetamine and benzodiazepine dependence predicted OMT interruption. Interrupters scored significantly higher on drug-taking and overdose during OMT but still had a significant 41% reduction in drug-related treatment, episodes. After interruption of treatment, such episodes increased markedly and were 3.6 times more frequent during the first post-OMT year compared to the pre-OMT period (p < 0.001). This increase was highest during the first months after OMT interruption. 2-5 years after interruption there was no significant increase. CONCLUSIONS: Increased somatic morbidity was found among OMT interrupters during the first year after OMT, and especially during the immediate post-treatment period.