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Papers by Lise Gluud

Research paper thumbnail of Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease)

Cochrane Database of Systematic Reviews, 2017

Background Alcohol-related liver disease is due to excessive alcohol consumption. It includes a s... more Background Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment of alcoholic hepatitis and other alcohol-related liver disease remains controversial. Objectives To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta-analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy in order to identify potential treatments. However, even in the subgroup of participants when the potential effect modifiers appeared reasonably similar across comparisons, there was evidence of inconsistency by one or more methods of assessment of inconsistency. Therefore, we did not report the results of the network meta-analysis and reported the comparative benefits and harms of different interventions using standard Cochrane methodology. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform and randomised controlled trials registers until February 2017 to identify randomised clinical trials on pharmacological treatments for alcohol-related liver diseases. Selection criteria Randomised clinical trials (irrespective of language, blinding, or publication status) including participants with alcohol-related liver disease. We excluded trials that included participants who had previously undergone liver transplantation and those with co-existing chronic viral diseases. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention.

Research paper thumbnail of Vitamin D supplementation for prevention of mortality in adults

Cochrane Database of Systematic Reviews, Oct 8, 2008

The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and h... more The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.

Research paper thumbnail of Plasma short chain fatty acids are associated with non-alcoholic fatty liver disease and fibrosis severity

Journal of Hepatology, Jun 1, 2023

Research paper thumbnail of Vitamin D supplementation for prevention of cancer in adults

Cochrane Database of Systematic Reviews, Oct 8, 2008

The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradic... more The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory. To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. Vitamin D could have been administered as supplemental vitamin D (vitamin D₃ (cholecalciferol) or vitamin D₂ (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), or 1,25-dihydroxyvitamin D (calcitriol)). Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors. Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review. There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on…

Research paper thumbnail of Low sphingolipid levels indicate poor survival in patients with alcohol-related liver disease

Journal of Hepatology, Jun 1, 2023

Research paper thumbnail of The CLIF-C AD-score predicts mortality in patients with non-decompensated cirrhosis

Zeitschrift Fur Gastroenterologie, 2019

Research paper thumbnail of Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Cochrane Database of Systematic Reviews, Apr 23, 2008

BACKGROUND: Our previous systematic review has demonstrated that antioxidant supplements may incr... more BACKGROUND: Our previous systematic review has demonstrated that antioxidant supplements may increase mortality. We have now updated this review. OBJECTIVES: To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults. METHODS: Search methods: We searched The Cochrane Library, Medline, Embase, Lilacs, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to February 2011. We scanned bibliographies of relevant publications and asked pharmaceutical companies for additional trials. Selection criteria: We included all primary and secondary prevention randomized clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Data collection and analysis: Three authors extracted data. Randomeffects and fixed-effect model meta-analyses were conducted. Risk of bias was considered in order to minimize the risk of systematic errors. Trial sequential analyses were conducted to minimize the risk of random errors. Random effects model meta-regression analyses were performed to assess sources of intertrial heterogeneity. MAIN RESULTS: Seventy-eight randomized trials with 296,707 participants were included. Fifty-six trials including 244,056 participants had low risk of bias. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel-group design, 30 the factorial design, and 2 the cross-over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I2-of 12%. In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertribal heterogeneity. Meta-regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention

Research paper thumbnail of Systemic inflammation is associated with cardiodynamic state in acute-on-chronic liver failure

Journal of Hepatology, Aug 1, 2020

Research paper thumbnail of Experience from a COVID-19 first-line referral clinic in Greater Copenhagen

Danish Medical Journal, Aug 7, 2020

Introduction: Due to the coronavirus disease 2019 (COVID-19) exposure in Denmark, first-line refe... more Introduction: Due to the coronavirus disease 2019 (COVID-19) exposure in Denmark, first-line referral centres were established to handle all patients suspected of COVID-19 or other upper respiratory tract infection. Here we report the first experiences from a first-line referral centre from Amager-Hvidovre Hospital, situated on the outskirts of Copenhagen. Methods: A retrospective quality assessment was performed with collection of symptom patterns and COVID-19 status. Results: During the first 24 days, a total of 3,551 patients were referred for assessment of symptoms of upper respiratory tract infection and COVID-19. A total of 2,048 patients were assessed as having mild symptoms and referred for COVID-19 testing alone, whereas 337 patients were assessed clinically by a physician. Thirty-seven were positive for COVID-19 infection, 286 were negative. The most common symptoms reported were fever, coughing and dyspnoea. Fever was an independent predictor of COVID-19 infection (odds ratio (OR) = 2.25 (95% confidence interval (CI): 1.08-5.04); p = 0.037); whereas sore throat was not (OR = 0.40 (95% CI: 0.15-0.92); p = 0.045). Only a small number of patients reported loss of taste or anosmia. In total, 113 patients were admitted to hospital, the majority of patients were discharged within 24 hours with mild symptoms of upper respiratory tract infections. Three of the COVID-19-positive patients developed a severe infection and two had a fatal outcome. Conclusions: The present study is the first to report the experiences and symptom patterns of a COVID-19 first-line referral centre with efficient triage of patients in need of hospitalisation. Funding: none. Trial registration: not relevant.

Research paper thumbnail of Vitamin D supplementation for prevention of mortality in adults

The Cochrane library, Jan 10, 2014

Data collection and analysis Six review authors extracted data independently. Random-effects and ... more Data collection and analysis Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors. To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses. Main results We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL).

Research paper thumbnail of Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Liver International, Mar 30, 2020

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, wh... more This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Hepatorenalt syndrom: diagnose, behandling og forebyggelse: diagnosis, treatment and prevention

Ugeskrift for Læger, 2013

Research paper thumbnail of Development and predictive validity of the cirrhosis-associated ascites symptom scale: A cohort study of 103 patients

World Journal of Gastroenterology, Apr 21, 2018

Gluud LL designed the study and drafted the protocol; Gluud LL, Jensen AS and Dahl EK collected q... more Gluud LL designed the study and drafted the protocol; Gluud LL, Jensen AS and Dahl EK collected questionnaires and conducted interviews for the pilot-testing of the cirrhosis-associated ascites symptom (CAS); Riedel AN, Jensen AS, Dahl EK, Gluud LL, Aamann L, Israelsen M and Kimer N collected questionnaires for the validation of CAS; Riedel AN and Gluud LL performed the analyses; Kimer N, Riedel AN and Gluud LL drafted the first version of the manuscript. All authors critically revised and approved of the final version of the manuscript.

Research paper thumbnail of Umbilical hernia repair in patients with cirrhosis: systematic review of mortality and complications

Research paper thumbnail of Endoscopic treatment with transmural drainage and necrosectomy for walled‐off necrosis provides favourable long‐term outcomes on pancreatic function

United European gastroenterology journal, Jun 1, 2020

Background and aims: Several studies have shown improved short-term outcome with endoscopic trans... more Background and aims: Several studies have shown improved short-term outcome with endoscopic transmural drainage and necrosectomy for the treatment of walled-off pancreatic necrosis. However, knowledge on the longterm prognosis after such treatment is limited. The aim of present study was to evaluate long-term outcomes in patients endoscopically treated with transmural drainage and necrosectomy. Methods: We retrospectively follow up 125 patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy in 2010-2017. All patients received plastic pigtail stents and nasocystic catheter. Additional external drainage was performed in 41 patients. Main outcomes were survival, pancreatic function, development of co-morbidities, ability to work and social status. Results: During a median follow-up of 4.3 years, nine (7%) patients died. Seven deaths were unrelated to pancreatic disease, and two patients died of pancreatic cancer. Twenty-two (18%) patients developed exocrine pancreatic insufficiency. Thirty-six (32%) previous non-diabetics developed endocrine insufficiency. Endoscopic necrosectomy during admission (odds ratio (OR) ¼ 1.28, 95% confidence interval (CI) 1.05-1.56; p ¼ 0.015) and therapy on the main pancreatic duct (OR ¼ 8.08, 95% CI 2.43-26.9; p < 0.001) during follow-up predicted development of exocrine insufficiency. Severity on computed tomography predicted endocrine insufficiency (OR ¼ 1.61, 95% CI 1.24-2.09; p < 0.001). Most patients regained their working capacity and preserved their marital status. Conclusions: This study provides robust data on the long-term outcome of patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy. The favourable outcomes on survival, pancreatic function and social status support current recommendations of endoscopic transmural drainage and necrosectomy being the treatment of choice for walled-off pancreatic necrosis.

Research paper thumbnail of Characterisation of the fibroinflammatory process involved in progression from acute to chronic pancreatitis: study protocol for a multicentre, prospective cohort study

BMJ Open, Aug 1, 2019

Characterisation of the fibroinflammatory process involved in progression from acute to chronic p... more Characterisation of the fibroinflammatory process involved in progression from acute to chronic pancreatitis: study protocol for a multicentre, prospective cohort study. BMJ Open 2019;9:e028999.

Research paper thumbnail of Long-term changes of pancreatic function in patients with complicated walled-off necrosis

Scandinavian Journal of Gastroenterology

Research paper thumbnail of Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: Case report on three family members

Pancreatology, 2020

Background/Objectives: Abdominal pain is one of the known symptoms associated with coronavirus di... more Background/Objectives: Abdominal pain is one of the known symptoms associated with coronavirus disease 2019. Little is known about the development of acute pancreatitis as a complication of severe acute respiratory syndrome coronavirus 2 infection. This case report describes the presentation of acute pancreatitis in two of three family members with severe COVID-19 infection. Methods: Data were collected from three family members admitted with COVID-19 to the intensive care unit in March 2020. This study was reviewed and approved by the local data and ethics committee (31-1521-253). Results: Two of the three family members were diagnosed with acute pancreatitis associated with SARS-CoV-2. Other causes of acute pancreatitis were excluded for both patients (including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension). Conclusions: These cases highlight acute pancreatitis as a complication associated with COVID-19 and underlines the importance of measuring pancreas-specific plasma amylase in patients with COVID-19 and abdominal pain.

Research paper thumbnail of Modified Marshall Score Predicts Mortality in Patients With Walled-off Pancreatic Necrosis Treated in an Intensive Care Unit

Research paper thumbnail of Energy expenditure and loss of muscle and fat mass in patients with walled-off pancreatic necrosis: a prospective study

Pancreatology, 2019

Ensuring adequate nutritional support in patients with walled-off pancreatic necrosis (WON) is ch... more Ensuring adequate nutritional support in patients with walled-off pancreatic necrosis (WON) is challenging and weight loss is often considerable. The aim of this study was to evaluate resting energy expenditure (REE) and body composition in patients with WON. Methods: We prospectively included 18 patients (67% men; median age 63 y; 44% gallstones; 39% alcohol) with WON undergoing endoscopic transgastric drainage and necrosectomy. Patients were followed for 4 wk after admission. We assessed hand-grip strength, REE using indirect calorimetry, and body composition with dual-energy x-ray absorptiometry to assess the percentage change in muscle mass (MM) and fat mass (FM). Data are summarized using medians (range). Results: At baseline, the median body mass index was 27.9 kg/m 2 (17.7À35.6 kg/m 2). Fifteen patients (83%) had infected WON. Eight patients (44%) received total or supplemental parenteral nutrition. The median percentage loss in MM was 0.31% and FM was 6.2%. The median REE was 6870 kJ (3255À8870 kJ) at baseline. Compared with the predicted REE, the measured REE was 1049 kJ higher (À3065 to 2126 kJ) at baseline and À951 kJ lower (À2600 to 3202 kJ) at 4 wk. The difference between the predicted and measured REE at baseline was correlated with the percentage loss in MM (P = 0.043) and FM (P = 0.026). Additionally, patients with infected WON had significantly higher REE (P = 0.003). Conclusion: In patients with WON, an increased REE appears to predict increased muscle and fat loss. Additional studies are necessary to evaluate if REE may be used to improve nutritional support.

Research paper thumbnail of Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease)

Cochrane Database of Systematic Reviews, 2017

Background Alcohol-related liver disease is due to excessive alcohol consumption. It includes a s... more Background Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment of alcoholic hepatitis and other alcohol-related liver disease remains controversial. Objectives To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta-analysis and to generate rankings of the available pharmacological interventions according to their safety and efficacy in order to identify potential treatments. However, even in the subgroup of participants when the potential effect modifiers appeared reasonably similar across comparisons, there was evidence of inconsistency by one or more methods of assessment of inconsistency. Therefore, we did not report the results of the network meta-analysis and reported the comparative benefits and harms of different interventions using standard Cochrane methodology. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform and randomised controlled trials registers until February 2017 to identify randomised clinical trials on pharmacological treatments for alcohol-related liver diseases. Selection criteria Randomised clinical trials (irrespective of language, blinding, or publication status) including participants with alcohol-related liver disease. We excluded trials that included participants who had previously undergone liver transplantation and those with co-existing chronic viral diseases. We considered any of the various pharmacological interventions compared with each other or with placebo or no intervention.

Research paper thumbnail of Vitamin D supplementation for prevention of mortality in adults

Cochrane Database of Systematic Reviews, Oct 8, 2008

The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and h... more The available evidence on vitamin D and mortality is inconclusive. To assess the beneficial and harmful effects of vitamin D for prevention of mortality in adults. We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science (to January 2011). We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention. Vitamin D could have been administered as supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol) or 1,25-dihydroxyvitamin D (calcitriol)). Six authors extracted data independently. Random-effects and fixed-effect model meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RR). To account for trials with zero events, meta-analyses of dichotomous data were repeated using risk differences (RD) and empirical continuity corrections. Risk of bias was considered in order to minimise risk of systematic errors. Trial sequential analyses were conducted to minimise the risk of random errors. Fifty randomised trials with 94,148 participants provided data for the mortality analyses. Most trials included elderly women (older than 70 years). Vitamin D was administered for a median of two years. More than one half of the trials had a low risk of bias. Overall, vitamin D decreased mortality (RR 0.97, 95% confidence interval (CI) 0.94 to 1.00, I(2) = 0%). When the different forms of vitamin D were assessed separately, only vitamin D(3) decreased mortality significantly (RR 0.94, 95% CI 0.91 to 0.98, I(2) = 0%; 74,789 participants, 32 trials) whereas vitamin D(2), alfacalcidol, or calcitriol did not. Trial sequential analysis supported our finding regarding vitamin D(3), corresponding to 161 individuals treated to prevent one additional death. Vitamin D(3) combined with calcium increased the risk of nephrolithiasis (RR 1.17, 95% CI 1.02 to 1.34, I(2) = 0%). Alfacalcidol and calcitriol increased the risk of hypercalcaemia (RR 3.18, 95% CI 1.17 to 8.68, I(2) = 17%). Data on health-related quality of life and health economics were inconclusive. Vitamin D in the form of vitamin D(3) seems to decrease mortality in predominantly elderly women who are mainly in institutions and dependent care. Vitamin D(2), alfacalcidol, and calcitriol had no statistically significant effect on mortality. Vitamin D(3) combined with calcium significantly increased nephrolithiasis. Both alfacalcidol and calcitriol significantly increased hypercalcaemia.

Research paper thumbnail of Plasma short chain fatty acids are associated with non-alcoholic fatty liver disease and fibrosis severity

Journal of Hepatology, Jun 1, 2023

Research paper thumbnail of Vitamin D supplementation for prevention of cancer in adults

Cochrane Database of Systematic Reviews, Oct 8, 2008

The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradic... more The evidence on whether vitamin D supplementation is effective in decreasing cancers is contradictory. To assess the beneficial and harmful effects of vitamin D supplementation for prevention of cancer in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, Science Citation Index Expanded, and the Conference Proceedings Citation Index-Science to February 2014. We scanned bibliographies of relevant publications and asked experts and pharmaceutical companies for additional trials. We included randomised trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults who were healthy or were recruited among the general population, or diagnosed with a specific disease. Vitamin D could have been administered as supplemental vitamin D (vitamin D₃ (cholecalciferol) or vitamin D₂ (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), or 1,25-dihydroxyvitamin D (calcitriol)). Two review authors extracted data independently. We conducted random-effects and fixed-effect model meta-analyses. For dichotomous outcomes, we calculated the risk ratios (RRs). We considered risk of bias in order to assess the risk of systematic errors. We conducted trial sequential analyses to assess the risk of random errors. Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review. There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on…

Research paper thumbnail of Low sphingolipid levels indicate poor survival in patients with alcohol-related liver disease

Journal of Hepatology, Jun 1, 2023

Research paper thumbnail of The CLIF-C AD-score predicts mortality in patients with non-decompensated cirrhosis

Zeitschrift Fur Gastroenterologie, 2019

Research paper thumbnail of Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases

Cochrane Database of Systematic Reviews, Apr 23, 2008

BACKGROUND: Our previous systematic review has demonstrated that antioxidant supplements may incr... more BACKGROUND: Our previous systematic review has demonstrated that antioxidant supplements may increase mortality. We have now updated this review. OBJECTIVES: To assess the beneficial and harmful effects of antioxidant supplements for prevention of mortality in adults. METHODS: Search methods: We searched The Cochrane Library, Medline, Embase, Lilacs, the Science Citation Index Expanded, and Conference Proceedings Citation Index-Science to February 2011. We scanned bibliographies of relevant publications and asked pharmaceutical companies for additional trials. Selection criteria: We included all primary and secondary prevention randomized clinical trials on antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Data collection and analysis: Three authors extracted data. Randomeffects and fixed-effect model meta-analyses were conducted. Risk of bias was considered in order to minimize the risk of systematic errors. Trial sequential analyses were conducted to minimize the risk of random errors. Random effects model meta-regression analyses were performed to assess sources of intertrial heterogeneity. MAIN RESULTS: Seventy-eight randomized trials with 296,707 participants were included. Fifty-six trials including 244,056 participants had low risk of bias. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase. The mean age was 63 years (range 18 to 103 years). The mean proportion of women was 46%. Of the 78 trials, 46 used the parallel-group design, 30 the factorial design, and 2 the cross-over design. All antioxidants were administered orally, either alone or in combination with vitamins, minerals, or other interventions. The duration of supplementation varied from 28 days to 12 years (mean duration 3 years; median duration 2 years). Overall, the antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (21,484 dead/183,749 (11.7%) versus 11,479 dead/112,958 (10.2%); 78 trials, relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05) but significantly increased mortality in a fixed-effect model (RR 1.03, 95% CI 1.01 to 1.05). Heterogeneity was low with an I2-of 12%. In meta-regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertribal heterogeneity. Meta-regression analysis did not find a significant difference in the estimated intervention effect in the primary prevention and the secondary prevention

Research paper thumbnail of Systemic inflammation is associated with cardiodynamic state in acute-on-chronic liver failure

Journal of Hepatology, Aug 1, 2020

Research paper thumbnail of Experience from a COVID-19 first-line referral clinic in Greater Copenhagen

Danish Medical Journal, Aug 7, 2020

Introduction: Due to the coronavirus disease 2019 (COVID-19) exposure in Denmark, first-line refe... more Introduction: Due to the coronavirus disease 2019 (COVID-19) exposure in Denmark, first-line referral centres were established to handle all patients suspected of COVID-19 or other upper respiratory tract infection. Here we report the first experiences from a first-line referral centre from Amager-Hvidovre Hospital, situated on the outskirts of Copenhagen. Methods: A retrospective quality assessment was performed with collection of symptom patterns and COVID-19 status. Results: During the first 24 days, a total of 3,551 patients were referred for assessment of symptoms of upper respiratory tract infection and COVID-19. A total of 2,048 patients were assessed as having mild symptoms and referred for COVID-19 testing alone, whereas 337 patients were assessed clinically by a physician. Thirty-seven were positive for COVID-19 infection, 286 were negative. The most common symptoms reported were fever, coughing and dyspnoea. Fever was an independent predictor of COVID-19 infection (odds ratio (OR) = 2.25 (95% confidence interval (CI): 1.08-5.04); p = 0.037); whereas sore throat was not (OR = 0.40 (95% CI: 0.15-0.92); p = 0.045). Only a small number of patients reported loss of taste or anosmia. In total, 113 patients were admitted to hospital, the majority of patients were discharged within 24 hours with mild symptoms of upper respiratory tract infections. Three of the COVID-19-positive patients developed a severe infection and two had a fatal outcome. Conclusions: The present study is the first to report the experiences and symptom patterns of a COVID-19 first-line referral centre with efficient triage of patients in need of hospitalisation. Funding: none. Trial registration: not relevant.

Research paper thumbnail of Vitamin D supplementation for prevention of mortality in adults

The Cochrane library, Jan 10, 2014

Data collection and analysis Six review authors extracted data independently. Random-effects and ... more Data collection and analysis Six review authors extracted data independently. Random-effects and fixed-effect meta-analyses were conducted. For dichotomous outcomes, we calculated the risk ratios (RRs). To account for trials with zero events, we performed meta-analyses of dichotomous data using risk differences (RDs) and empirical continuity corrections. We used published data and data obtained by contacting trial authors. To minimise the risk of systematic error, we assessed the risk of bias of the included trials. Trial sequential analyses controlled the risk of random errors possibly caused by cumulative meta-analyses. Main results We identified 159 randomised clinical trials. Ninety-four trials reported no mortality, and nine trials reported mortality but did not report in which intervention group the mortality occurred. Accordingly, 56 randomised trials with 95,286 participants provided usable data on mortality. The age of participants ranged from 18 to 107 years. Most trials included women older than 70 years. The mean proportion of women was 77%. Forty-eight of the trials randomly assigned 94,491 healthy participants. Of these, four trials included healthy volunteers, nine trials included postmenopausal women and 35 trials included older people living on their own or in institutional care. The remaining eight trials randomly assigned 795 participants with neurological, cardiovascular, respiratory or rheumatoid diseases. Vitamin D was administered for a weighted mean of 4.4 years. More than half of the trials had a low risk of bias. All trials were conducted in high-income countries. Forty-five trials (80%) reported the baseline vitamin D status of participants based on serum 25-hydroxyvitamin D levels. Participants in 19 trials had vitamin D adequacy (at or above 20 ng/mL). Participants in the remaining 26 trials had vitamin D insufficiency (less than 20 ng/mL).

Research paper thumbnail of Cardiodynamic state is associated with systemic inflammation and fatal acute‐on‐chronic liver failure

Liver International, Mar 30, 2020

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, wh... more This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Research paper thumbnail of Hepatorenalt syndrom: diagnose, behandling og forebyggelse: diagnosis, treatment and prevention

Ugeskrift for Læger, 2013

Research paper thumbnail of Development and predictive validity of the cirrhosis-associated ascites symptom scale: A cohort study of 103 patients

World Journal of Gastroenterology, Apr 21, 2018

Gluud LL designed the study and drafted the protocol; Gluud LL, Jensen AS and Dahl EK collected q... more Gluud LL designed the study and drafted the protocol; Gluud LL, Jensen AS and Dahl EK collected questionnaires and conducted interviews for the pilot-testing of the cirrhosis-associated ascites symptom (CAS); Riedel AN, Jensen AS, Dahl EK, Gluud LL, Aamann L, Israelsen M and Kimer N collected questionnaires for the validation of CAS; Riedel AN and Gluud LL performed the analyses; Kimer N, Riedel AN and Gluud LL drafted the first version of the manuscript. All authors critically revised and approved of the final version of the manuscript.

Research paper thumbnail of Umbilical hernia repair in patients with cirrhosis: systematic review of mortality and complications

Research paper thumbnail of Endoscopic treatment with transmural drainage and necrosectomy for walled‐off necrosis provides favourable long‐term outcomes on pancreatic function

United European gastroenterology journal, Jun 1, 2020

Background and aims: Several studies have shown improved short-term outcome with endoscopic trans... more Background and aims: Several studies have shown improved short-term outcome with endoscopic transmural drainage and necrosectomy for the treatment of walled-off pancreatic necrosis. However, knowledge on the longterm prognosis after such treatment is limited. The aim of present study was to evaluate long-term outcomes in patients endoscopically treated with transmural drainage and necrosectomy. Methods: We retrospectively follow up 125 patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy in 2010-2017. All patients received plastic pigtail stents and nasocystic catheter. Additional external drainage was performed in 41 patients. Main outcomes were survival, pancreatic function, development of co-morbidities, ability to work and social status. Results: During a median follow-up of 4.3 years, nine (7%) patients died. Seven deaths were unrelated to pancreatic disease, and two patients died of pancreatic cancer. Twenty-two (18%) patients developed exocrine pancreatic insufficiency. Thirty-six (32%) previous non-diabetics developed endocrine insufficiency. Endoscopic necrosectomy during admission (odds ratio (OR) ¼ 1.28, 95% confidence interval (CI) 1.05-1.56; p ¼ 0.015) and therapy on the main pancreatic duct (OR ¼ 8.08, 95% CI 2.43-26.9; p < 0.001) during follow-up predicted development of exocrine insufficiency. Severity on computed tomography predicted endocrine insufficiency (OR ¼ 1.61, 95% CI 1.24-2.09; p < 0.001). Most patients regained their working capacity and preserved their marital status. Conclusions: This study provides robust data on the long-term outcome of patients with walled-off pancreatic necrosis treated with endoscopic transmural drainage and necrosectomy. The favourable outcomes on survival, pancreatic function and social status support current recommendations of endoscopic transmural drainage and necrosectomy being the treatment of choice for walled-off pancreatic necrosis.

Research paper thumbnail of Characterisation of the fibroinflammatory process involved in progression from acute to chronic pancreatitis: study protocol for a multicentre, prospective cohort study

BMJ Open, Aug 1, 2019

Characterisation of the fibroinflammatory process involved in progression from acute to chronic p... more Characterisation of the fibroinflammatory process involved in progression from acute to chronic pancreatitis: study protocol for a multicentre, prospective cohort study. BMJ Open 2019;9:e028999.

Research paper thumbnail of Long-term changes of pancreatic function in patients with complicated walled-off necrosis

Scandinavian Journal of Gastroenterology

Research paper thumbnail of Coronavirus Disease-19 (COVID-19) associated with severe acute pancreatitis: Case report on three family members

Pancreatology, 2020

Background/Objectives: Abdominal pain is one of the known symptoms associated with coronavirus di... more Background/Objectives: Abdominal pain is one of the known symptoms associated with coronavirus disease 2019. Little is known about the development of acute pancreatitis as a complication of severe acute respiratory syndrome coronavirus 2 infection. This case report describes the presentation of acute pancreatitis in two of three family members with severe COVID-19 infection. Methods: Data were collected from three family members admitted with COVID-19 to the intensive care unit in March 2020. This study was reviewed and approved by the local data and ethics committee (31-1521-253). Results: Two of the three family members were diagnosed with acute pancreatitis associated with SARS-CoV-2. Other causes of acute pancreatitis were excluded for both patients (including alcohol, biliary obstruction/gall stones, drugs, trauma, hypertriglyceridemia, hypercalcemia, and hypotension). Conclusions: These cases highlight acute pancreatitis as a complication associated with COVID-19 and underlines the importance of measuring pancreas-specific plasma amylase in patients with COVID-19 and abdominal pain.

Research paper thumbnail of Modified Marshall Score Predicts Mortality in Patients With Walled-off Pancreatic Necrosis Treated in an Intensive Care Unit

Research paper thumbnail of Energy expenditure and loss of muscle and fat mass in patients with walled-off pancreatic necrosis: a prospective study

Pancreatology, 2019

Ensuring adequate nutritional support in patients with walled-off pancreatic necrosis (WON) is ch... more Ensuring adequate nutritional support in patients with walled-off pancreatic necrosis (WON) is challenging and weight loss is often considerable. The aim of this study was to evaluate resting energy expenditure (REE) and body composition in patients with WON. Methods: We prospectively included 18 patients (67% men; median age 63 y; 44% gallstones; 39% alcohol) with WON undergoing endoscopic transgastric drainage and necrosectomy. Patients were followed for 4 wk after admission. We assessed hand-grip strength, REE using indirect calorimetry, and body composition with dual-energy x-ray absorptiometry to assess the percentage change in muscle mass (MM) and fat mass (FM). Data are summarized using medians (range). Results: At baseline, the median body mass index was 27.9 kg/m 2 (17.7À35.6 kg/m 2). Fifteen patients (83%) had infected WON. Eight patients (44%) received total or supplemental parenteral nutrition. The median percentage loss in MM was 0.31% and FM was 6.2%. The median REE was 6870 kJ (3255À8870 kJ) at baseline. Compared with the predicted REE, the measured REE was 1049 kJ higher (À3065 to 2126 kJ) at baseline and À951 kJ lower (À2600 to 3202 kJ) at 4 wk. The difference between the predicted and measured REE at baseline was correlated with the percentage loss in MM (P = 0.043) and FM (P = 0.026). Additionally, patients with infected WON had significantly higher REE (P = 0.003). Conclusion: In patients with WON, an increased REE appears to predict increased muscle and fat loss. Additional studies are necessary to evaluate if REE may be used to improve nutritional support.