| 1. |
- Sundbom, Magnus, et al.
(författare)
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Substantial Decrease in Comorbidity 5 Years After Gastric Bypass: A Population-based Study From the Scandinavian Obesity Surgery Registry.
- 2017
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Ingår i: Annals of Surgery. - Philadelphia PA, USA : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 265:6, s. 1166-1171
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate effect on comorbid disease and weight loss 5 years after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity in a large nationwide cohort. Background: The number patients having surgical procedures to treat obesity and obesity-related disease are increasing. Yet, population-based, long-term outcome studies are few. Methods: Data on 26,119 individuals [75.8% women, 41.0 years, and body mass index (BMI) 42.8 kg/m2] undergoing primary RYGB between May 1, 2007 and June 30, 2012, were collected from 2 Swedish quality registries: Scandinavian Obesity Surgery Registry and the Prescribed Drug Registry. Weight, remission of type 2 diabetes mellitus, hypertension, dyslipidemia, depression, and sleep apnea, and changes in corresponding laboratory data were studied. Five-year follow-up was 100% (9774 eligible individuals) for comorbid diseases. Results: BMI decreased from 42.8 ± 5.5 to 31.2 ± 5.5 kg/m2 at 5 years, corresponding to 27.7% reduction in total body weight. Prevalence of type 2 diabetes mellitus (15.5%–5.9%), hypertension (29.7%–19.5%), dyslipidemia (14.0%–6.8%), and sleep apnea (9.6%–2.6%) was reduced. Greater weight loss was a positive prognostic factor, whereas increasing age or BMI at baseline was a negative prognostic factor for remission. The use of antidepressants increased (24.1%–27.5%). Laboratory status was improved, for example, fasting glucose and glycated hemoglobin decreased from 6.1 to 5.4 mmol/mol and 41.8% to 37.7%, respectively. Conclusions: In this nationwide study, gastric bypass resulted in large improvements in obesity-related comorbid disease and sustained weight loss over a 5-year period. The increased use of antidepressants warrants further investigation. Studies with long-term results after bariatric surgery are surprisingly rare, 1–5 especially in the light of the large number of procedures performed worldwide. In most studies there is a 1 to 2-year follow-up, 6 and at such an early point in time, it is impossible to evaluate the true effect of gastric bypass, because patients have just reached their nadir in weight. Moreover, for this group of patients, the longstanding remission of obesity-related comorbidities, for example, diabetes mellitus, hypertension, dyslipidemia, and sleep apnea, are of utmost importance. The Scandinavian Obesity Surgery Registry (SOReg) was launched in 2007 as a quality registry for the expanding number of bariatric surgeries in Sweden. 7 In 2015, SOReg contained more than 50,000 bariatric procedures (>98% national coverage), with all 43 operating centers reporting to the registry. There has been an expansion of bariatric surgery, with 3300 bariatric procedures performed in 2008, 4800 in 2009, 7800 in 2010, and 8600 in 2011. There has been a slight decrease in procedures, and currently approximately 7000 performed annually, and approximately 95% of the reported procedures have been primary laparoscopic gastric bypass. 8 Perioperative complication rates (eg, 1.2% leaks) and mortality are low (0.04%), the latter validated with the Swedish Population Register. Regular audits are performed by randomly comparing data in SOReg with patient charts at the surgical centers, demonstrating a high validity with less than 2% incorrect values. 7 Furthermore, by cross-linkage with the national Prescribed Drug Registry (PDR), a 100% follow-up of the occurrence of comorbid disease (defined as medical treatment) can be achieved. The present study reports outcome in weight and obesity-related comorbid disease in a nationwide cohort of 26,119 individuals over 5 years after primary Roux-en-Y gastric bypass (RYGB) in Sweden, using the prospective SOReg database with cross-linkage with the PDR.
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| 2. |
- Berglind, Daniel, et al.
(författare)
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Longitudinal assessment of physical activity in women undergoing Roux-en-Y gastric bypass
- 2015
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Ingår i: Obesity Surgery. - : Springer Science and Business Media LLC. - 0960-8923 .- 1708-0428. ; 25:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients undergoing bariatric surgery do not seem to increase objectively measured physical activity (PA) after surgery, despite substantial weight loss. The aims of the present study were (i) to objectively characterize 3 months pre-surgery to 9 months postsurgery PA and sedentary behavior changes in women undergoing Roux-en-Y gastric bypass (RYGB) using tri-axial accelerometers and (ii) to examine associations between pre-surgery versus postsurgery PA and sedentary behavior with anthropometric measures taken in home environment.Methods: Fifty-six women, with an average pre-surgery body mass index (BMI) of 37.6 (SD 2.6) and of age 39.5 years (SD 5.7), were recruited at five Swedish hospitals. PA was measured for 1 week by the Actigraph GT3X+ accelerometer, and anthropometric measures were taken at home visits 3 months pre-surgery and 9 months postsurgery, thus limiting seasonal effects.Results: Average BMI loss, 9 months postsurgery, was 11.7 (SD 2.7) BMI units. There were no significant pre- to postsurgery differences in PA or sedentary behavior. However, pre-surgery PA showed negative association with PA change and positive association with postsurgery PA. Adjustments for pre-surgery BMI had no impact on these associations.Conclusions: No significant differences were observed in objectively measured changes in PA or time spent sedentary from 3 months pre-surgery to 9 months postsurgery among women undergoing RYGB. However, women with higher pre-surgery PA decreased their PA postsurgery while women with lower pre-surgery PA increased their PA.
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| 3. |
- Hagsäter, S Melker, et al.
(författare)
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A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear
- 2021
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 24:9, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- Background: Though drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A-acting drugs locally into different brain regions, reports on the effect of systemic administration of 5-HT2A receptor agonists and 5-HT2A antagonists or inverse agonists on this behavior remain sparse. Methods: We assessed the possible impact of systemic administration of 5-HT2A receptor agonists, 5-HT2A receptor inverse agonists, and a selective serotonin reuptake inhibitor (SSRI)-per se or in combination-on the freezing displayed by male rats when re-exposed to a conditioning chamber in which they received foot shocks 7 days earlier. Results: The 5-HT2A receptor agonists psilocybin and 25CN-NBOH induced a reduction in conditioned fear that was countered by pretreatment with 5-HT2A receptor inverse agonist MDL 100907. While both MDL 100907 and another 5-HT2A receptor inverse agonist, pimavanserin, failed to impact freezing per se, both compounds unmasked a robust fear-reducing effect of an SSRI, escitalopram, which by itself exerted no such effect. Conclusions: The results indicate that 5-HT2A receptor activation is not a prerequisite for normal conditioned freezing in rats but that this receptor subtype, when selectively over-activated prior to expression, exerts a marked fear-reducing influence. However, in the presence of an SSRI, the 5-HT2A receptor, on the contrary, appears to counter an anti-freezing effect of the enhanced extracellular serotonin levels following reuptake inhibition.
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| 4. |
- Hansson, Caroline, 1981, et al.
(författare)
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Ghrelin Influences Novelty Seeking Behavior in Rodents and Men
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Recent discoveries indicate an important role for ghrelin in drug and alcohol reward and an ability of ghrelin to regulate mesolimbic dopamine activity. The role of dopamine in novelty seeking, and the association between this trait and drug and alcohol abuse, led us to hypothesize that ghrelin may influence novelty seeking behavior. To test this possibility we applied several complementary rodent models of novelty seeking behavior, i.e. inescapable novelty-induced locomotor activity (NILA), novelty-induced place preference and novel object exploration, in rats subjected to acute ghrelin receptor (growth hormone secretagogue receptor; GHSR) stimulation or blockade. Furthermore we assessed the possible association between polymorphisms in the genes encoding ghrelin and GHSR and novelty seeking behavior in humans. The rodent studies indicate an important role for ghrelin in a wide range of novelty seeking behaviors. Ghrelin-injected rats exhibited a higher preference for a novel environment and increased novel object exploration. Conversely, those with GHSR blockade drastically reduced their preference for a novel environment and displayed decreased NILA. Importantly, the mesolimbic ventral tegmental area selective GHSR blockade was sufficient to reduce the NILA response indicating that the mesolimbic GHSRs might play an important role in the observed novelty responses. Moreover, in untreated animals, a striking positive correlation between NILA and sucrose reward behavior was detected. Two GHSR single nucleotide polymorphisms (SNPs), rs2948694 and rs495225, were significantly associated with the personality trait novelty seeking, as assessed using the Temperament and Character Inventory (TCI), in human subjects. This study provides the first evidence for a role of ghrelin in novelty seeking behavior in animals and humans, and also points to an association between food reward and novelty seeking in rodents. Citation: Hansson C, Shirazi RH, Naslund J, Vogel H, Neuber C, et al. (2012) Ghrelin Influences Novelty Seeking Behavior in Rodents and Men. PLoS ONE 7(12): e50409. doi:10.1371/journal.pone.0050409
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| 5. |
- Hedberg, Jakob, 1972-
(författare)
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Gastrointestinal Physiology and Results following Bariatric Surgery
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The number of operations for morbid obesity is rising fast. We have examined aspects of postoperative physiology and results after bariatric surgery. The pH in the proximal pouch after Roux-en-Y gastric bypass (RYGBP) was investigated with catheter-based and wire-less technique. Gastric emptying, PYY-levels in the fasting state and after a standardized meal was evaluated after biliopancreatic diversion with duodenal switch (DS). A clinical trial was undertaken, comparing DS to RYGBP in patients with BMI>48. Main outcome variables were safety and long-term weight results as well as abdominal symptoms and laboratory results. Patients with stomal ulcer had significantly lower pH in their proximal gastric pouch as compared to asymptomatic control subjects. Long-time pH measurements with the wire-less BRAVO-system were feasible and demonstrated pH<4 in median 10.5% of the time in asymptomatic post-RYGBP patients. After DS, the T50 of gastric emptying was 28±16 minutes. PYY-levels were higher after DS than in age-matched control subjects. BMI-reduction was greater after DS (24 BMI-units) than after RYGBP (17 BMI-units) in median 3.5 (2.0-5.3) years after surgery (p<0.001). Fasting glucose and HbA1c levels were lower one and three years after DS as compared to RYGBP. On the other hand, DS-patients reported having more diarrhea and malodorous flatus. This thesis has resulted in deepened knowledge. Acid produced in the proximal pouch is an important pathogenetic factor in the development of stomal ulcer after RYGBP. However, symptom-free patients have an acidic environment in the proximal Roux-limb as well. After DS, gastric emptying is fast, but not instantaneous, and PYY-levels are high. DS results in superior weight reduction and better glucose control as compared to RYGBP in patients with BMI>48. We believe that DS has a place in surgical treatment of the super-obese, even though symptoms of diarrhea and malodorous flatus are more common after DS.
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| 6. |
- Hieronymus, F., et al.
(författare)
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Determining maximal achievable effect sizes of antidepressant therapies in placebo-controlled trials
- 2021
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 144:3, s. 300-309
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Tidskriftsartikel (refereegranskat)abstract
- Objective Antidepressants outperform placebo with an effect size of around 0.30. It has been suggested that effect sizes as high as 0.875 are necessary for a minimal clinically important difference. Whether such effect sizes are achievable in placebo-controlled trials is unknown. Therefore, we aimed to assess what effect sizes are theoretically achievable in placebo-controlled trials of antidepressants. Methods Patient-level analyses comparing Hamilton Depression Rating Scale (HDRS-17) outcomes for simulated antidepressant therapies to placebo-treated participants (n = 2201) from clinical trials of selective serotonin reuptake inhibitors. Results An optimally effective antidepressant, where all treated participants achieve HDRS-17 scores comparable to those displayed by healthy volunteers (remission-type model), had a maximum effect size of 1.75, with a mean difference of 11.6 points on the HDRS-17. In simulations where patients received an additional 50% symptom reduction over that obtained with placebo (improvement-type model), the maximum effect size was 1.08 with a mean HDRS-17 difference of 7.2. When adjusting for normal rates of treatment discontinuation, maximum effect sizes were 1.10 (remission-type model) and 0.76 (improvement-type model) with HDRS-17 mean differences of 8.8 and 5.6, respectively. Conclusions Three methodological issues (i) a large and variable placebo response, (ii) a high rate of dropout and (iii) HDRS-17-ratings significantly larger than zero in healthy volunteers, reduce the degree of treatment-placebo separation achievable in depression trials. Assuming that those who discontinue treatment have only partial response, even a highly effective antidepressant would have difficulties surpassing such effect size cut-offs as have been suggested to signify a minimal clinically important difference.
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| 7. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
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GOOD NEWS REGARDING SSRI SAFETY IN DANISH META-ANALYSIS.
- 2020
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 32:1, s. 54-56
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Tidskriftsartikel (refereegranskat)abstract
- In two previous letters on an SSRI meta-analysis conducted by the Copenhagen Trial Unit at Copenhagen University Hospital, we have commented on a large number of errors, almost all of which have tilted the results in an anti-drug direction, that unfortunately mar this publication. While the authors have acknowledged many of these mishaps, and may now be expected to submit an extensive errata list to the journal where their paper was once published, we regretfully note that also their latest contribution to this exchange is surprisingly inaccurate. However, its many shortcomings notwithstanding, their meta-analysis does add to the current literature by confirming that SSRIs do not seem to enhance the risk for suicide or death, and also that these drugs seem to enhance the risk of side effects categorized as serious only in the elderly.
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| 8. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
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Katakam and co-workers have not shown SSRIs to be harmful and ineffective and should stop claiming that they have.
- 2018
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 30:5, s. 266-274
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Tidskriftsartikel (refereegranskat)abstract
- Funded by the Danish state to provide guidance in health-related matters, the Copenhagen Trial Unit (CTU) at Rigshospitalet may cause considerable societal harm if allowing their analyses to be influenced by bias and prejudice rather than rigor and impartiality. This is why we found it worthwhile to comment on a report from the CTU in which the authors invoked analyses marred by numerous errors and methodological mistakes to claim that selective serotonin reuptake inhibitors (SSRIs) are harmful and ineffective. The CTU group has now produced a response to our comment which is on par with their original contribution in terms of bias, misconceptions and mistakes. Our conclusion is that the reputation of the CTU would be best served by the authors asking for retraction of their SSRI paper.
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| 9. |
- Hieronymus, Fredrik, 1986, et al.
(författare)
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Multiple possible inaccuracies cast doubt on a recent report suggesting selective serotonin reuptake inhibitors to be toxic and ineffective.
- 2018
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Ingår i: Acta Neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 30:5, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- According to a systematic review on the use of selective serotonin reuptake inhibitors (SSRIs) in adult depression that was recently published in BMC Psychiatry, the results of which have been widely disseminated in lay media, these drugs increase the risk for serious adverse events (SAEs) while exerting poor antidepressant efficacy. A cursory analysis, however, suggests the analysis of SAEs conducted by the authors to be marred by both methodological inaccuracies and blatant errors. After having corrected for these apparent mistakes, we conducted a sensitivity analysis in which we also accounted for a possible moderating effect of age; while this suggests SSRIs to be safe drugs in the non-elderly, they do confirm what is already known, that is, that they may enhance the risk for SAEs in the old. Given the loose definition of SAE, including also innocuous phenomena, the possible clinical significance of the latter observation, however, remains unclear until the nature and actual impact of the SAEs in question have been clarified. Moreover, with respect to efficacy, we find the paper in BMC Psychiatry misleading: first, the authors seem unaware of the well-established shortcomings associated with the conventional efficacy parameter on which their analysis is based, second, they have included suboptimal SSRI doses and third, they have missed some pivotal trials. Unless there are explanations for the many peculiarities in this paper that have escaped us, and which may be satisfactorily clarified by the authors, it seems important that the conclusions presented in this paper be publicly rectified.
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| 10. |
- Lisinski, Alexander, 1989, et al.
(författare)
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Item-based analysis of the effects of duloxetine in depression: a patient-level post hoc study
- 2020
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Ingår i: Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X .- 0893-133X. ; 45:3, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Oft-cited trial-level meta-analyses casting doubt on the usefulness of antidepressants have been based on re-analyses of to what extent the active drug has outperformed placebo in reducing the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) in clinical trials. Recent studies, however, suggest patient-level analyses of individual HDRS items to be more informative when assessing the efficacy of an antidepressant. To shed further light on both symptom-reducing and symptom-aggravating effects of a serotonin and noradrenaline reuptake inhibitor, duloxetine, when used for major depression in adults, we hence applied this approach to re-analyse data from 13 placebo-controlled trials. In addition, using patient-level data from 28 placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs), the response profile of duloxetine was compared to that of these drugs. Duloxetine induced a robust reduction in depressed mood that was not dependent on baseline severity and not caused by side-effects breaking the blind. A beneficial effect on depressed mood was at hand already after one week; when outcome was assessed using HDRS-17-sum as effect parameter, this early response was however masked by a concomitant deterioration with respect to adverse event-related items. No support for a suicide-provoking effect of duloxetine was obtained. The response profile of duloxetine was strikingly similar to that of the SSRIs. We conclude that the use of HDRS-17-sum as effect parameter underestimates the true efficacy and masks an early effect of duloxetine on core symptoms of depression. No support for major differences between duloxetine and SSRIs in clinical profile were obtained.
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