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Journal of the ASEAN Federation of... 2022The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous semaglutide as treatment for obesity in patients without diabetes.
METHODOLOGY
A comprehensive search of PubMed/MEDLINE, Cochrane and Google scholar was performed to identify trials on the efficacy and safety of subcutaneous semaglutide on patients with obesity without diabetes. Primary outcome was expressed as percent mean weight difference. Secondary outcomes including risk for gastrointestinal adverse events, discontinuation of treatment and serious adverse events were expressed as risk ratios. These were calculated using the random effects model.
RESULTS
The study included 4 randomized controlled trials having a total of 3,613 individuals with obesity without diabetes. The mean difference for weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI) (-12.81,-10.90), <0.00001]. Secondary outcomes showed that the risk of developing gastrointestinal adverse events was 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], <0.00001). Risk for discontinuation due to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], =0.001) and the risk for serious adverse events was 1.6 times more likely for semaglutide (RR1.60, 95%CI [1.24, 2.07], =0.0003). Serious events were mostly of gastrointestinal and hepatobiliary disorders such as acute pancreatitis and cholelithiasis.
CONCLUSION
Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared to placebo. This supports the use of semaglutide for weight management in obesity. However, risk of gastrointestinal adverse events, discontinuation of treatment and serious adverse events were higher in the semaglutide group versus placebo.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Acute Disease; Treatment Outcome; Double-Blind Method; Pancreatitis; Weight Loss; Obesity; Randomized Controlled Trials as Topic
PubMed: 36578889
DOI: 10.15605/jafes.037.02.14 -
Deutsches Arzteblatt International Jul 2022Acute pancreatitis (AP) is among the commonest non-malignant admission diagnoses in gastroenterology. Its incidence in Germany lies between 13 and 43 per 100 000...
BACKGROUND
Acute pancreatitis (AP) is among the commonest non-malignant admission diagnoses in gastroenterology. Its incidence in Germany lies between 13 and 43 per 100 000 inhabitants and is increasing. In 2017, 24 per 100 000 inhabitants were hospitalized for chronic pancreatitis.
METHODS
From October 2018 to January 2019, we systematically searched the literature for original articles, meta-analyses, and evidence-based guidelines that were published in German or English between 1960 and 2018.
RESULTS
30-50% of cases of acute pancreatitis are caused by gallstone disease, and another 30-50% are due to alcohol abuse. The diagnosis is made when at least two of the following three criteria are met: typical abdominal pain, elevation of serum lipase, and characteristic imaging findings. If those criteria are ambiguous, transabdominal sonography is indicated. The early initiation of food intake lowers the rate of infected pancreatic necrosis, organ failure, or death (odds ratio 0.44; 95% confidence interval [0.2; 0.96]). In AP, Ringer's lactate solution should be preferred for fluid resuscitation, at 200-250 mL/hr for 24 hours. Severe pain should be treated with opiates.
CONCLUSION
The current German clinical practice guideline reflects the developments in the diagnosis and treatment of pancreatitis that have taken place over the past few years. The long-term care and monitoring of patients with complication-free pancreatitis is the responsibility of primary care physicians and gastroenterologists.
Topics: Humans; Acute Disease; Fluid Therapy; Pancreatitis, Acute Necrotizing; Pancreatitis, Chronic; Meta-Analysis as Topic
PubMed: 35945698
DOI: 10.3238/arztebl.m2022.0223 -
Gastroenterology Jan 2022Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Acute pancreatitis is a common disease with significant associated morbidity and mortality. We performed a systematic review and meta-analysis of population-based studies to explore the changing temporal trends of acute pancreatitis incidence globally.
METHODS
We performed a systematic literature search to identify population-based studies reporting the annual incidence of acute pancreatitis. Abstracts were assessed independently to identify applicable articles for full-text review and data extraction. Joinpoint temporal trend analyses were performed to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs). The AAPCs were pooled in a meta-analysis to capture the overall and regional trends in acute pancreatitis incidence over time. Temporal data were summarized in a static map and an interactive, web-based map.
RESULTS
Forty-four studies reported the temporal incidence of acute pancreatitis (online interactive map: https://kaplan-acute-pancreatitis-ucalgary.hub.arcgis.com/). The incidence of acute pancreatitis has increased from 1961 to 2016 (AAPC, 3.07%; 95% CI, 2.30% to 3.84%; n = 34). Increasing incidence was observed in North America (AAPC, 3.67%; 95% CI, 2.76% to 4.57%; n = 4) and Europe (AAPC, 2.77%; 95% CI, 1.91% to 3.63%; n = 23). The incidence of acute pancreatitis was stable in Asia (AAPC, -0.28%; 95% CI, -5.03% to 4.47%; n = 4).
CONCLUSIONS
This meta-analysis provides a comprehensive overview of the global incidence of acute pancreatitis over the last 56 years and demonstrates a steadily rising incidence over time in most countries of the Western world. More studies are needed to better define the changing incidence of acute pancreatitis in Asia, Africa, and Latin America.
Topics: Acute Disease; Female; Global Health; Humans; Incidence; Male; Pancreatitis; Sex Distribution; Time Factors
PubMed: 34571026
DOI: 10.1053/j.gastro.2021.09.043 -
The American Journal of Medicine Jun 2022Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2... (Review)
Review
Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides >250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides >500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (<20 g total fat/d or <15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels >1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels >500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.
Topics: Acute Disease; Female; Humans; Hypertriglyceridemia; Pancreatitis; Plasmapheresis; Pregnancy; Triglycerides
PubMed: 35081380
DOI: 10.1016/j.amjmed.2021.12.006 -
EBioMedicine Aug 2022The causal association between cigarette smoking and several diseases remains equivocal. The purpose of this study was to appraise the causal role of smoking in a wide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The causal association between cigarette smoking and several diseases remains equivocal. The purpose of this study was to appraise the causal role of smoking in a wide range of diseases by summarizing the evidence from Mendelian randomization (MR) studies.
METHODS
MR studies on genetic liability to smoking initiation or lifetime smoking (composite of smoking initiation, heaviness, duration, and cessation) in relation to circulatory system, digestive system, nervous system, musculoskeletal system, endocrine, metabolic, and eye diseases, and neoplasms published until February 15, 2022, were identified in PubMed. De novo MR analyses were performed using summary statistics data from genome-wide association studies. Meta-analysis was applied to combine study-specific estimates.
FINDINGS
Meta-analyses of findings of 29 published MR studies and 123 de novo MR analyses of 57 distinct primary outcomes showed that genetic liability to smoking (smoking initiation or lifetime smoking) was associated with increased risk of 13 circulatory system diseases, several digestive system diseases (including diverticular, gallstone, gastroesophageal reflux, and Crohn's disease, acute pancreatitis, and periodontitis), epilepsy, certain musculoskeletal system diseases (including fracture, osteoarthritis, and rheumatoid arthritis), endocrine (polycystic ovary syndrome), metabolic (type 2 diabetes) and eye diseases (including age-related macular degeneration and senile cataract) as well as cancers of the lung, head and neck, esophagus, pancreas, bladder, kidney, cervix, and ovaries, and myeloid leukemia. Smoking liability was associated with decreased risk of Parkinson's disease and prostate cancer.
INTERPRETATION
This study found robust evidence that cigarette smoking causes a wide range of diseases.
FUNDING
This work was supported by research grants from the Swedish Cancer Society (Cancerfonden), the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council for Health, Working Life and Welfare (Forte, 2018-00123), and the Swedish Research Council (Vetenskapsrådet, 2019-00977). Stephen Burgess is supported by Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (204623/Z/16/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). The views expressed are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.
Topics: Acute Disease; Diabetes Mellitus, Type 2; Female; Genome-Wide Association Study; Humans; Male; Mendelian Randomization Analysis; Neoplasms; Pancreatitis; Polymorphism, Single Nucleotide; Smoking
PubMed: 35816897
DOI: 10.1016/j.ebiom.2022.104154 -
World Journal of Surgery Jun 2022Recommendations regarding the timing of cholecystectomy for acute biliary pancreatitis (ABP) require a systematic summary of current evidence to guide clinical practice.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recommendations regarding the timing of cholecystectomy for acute biliary pancreatitis (ABP) require a systematic summary of current evidence to guide clinical practice. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing early cholecystectomy (EC) versus delayed cholecystectomy (DC) in patients with ABP.
METHODS
We searched databases Medline, Embase, SCOPUS, Web of Science and Cochrane CENTRAL for randomized controlled trials addressing this question. Pairs of reviewers abstracted data and assessed the risk of bias in included studies. A random-effects meta-analysis was done to study the effect of the timing of cholecystectomy on outcomes of interest in patients with ABP. GRADE methodology was used to rate the quality in the body of evidence for each outcome as high, moderate, low, or very low.
RESULTS
11 randomized trials (1176 participants) were included. High-quality evidence from seven RCTs (867 participants) showed a statistically significant reduction in the risk for recurrent biliary events in favour of early cholecystectomy (RR 0.10, 95% CI 0.05 to 0.19, I = 0%). High-quality evidence from five trials was in favour of early cholecystectomy with a significant reduction in the risk 7of recurrent pancreatitis (RAP) in comparison to delayed cholecystectomy (RR 0.21, 95% CI 0.09 to 0.51, I = 0%).
CONCLUSION
This review showed that EC has definite advantages over DC in terms of reducing recurrent pancreaticobiliary events and LOS following mild ABP. However, more RCTs are required to study the role of EC in patients with moderately-severe and severe ABP. Trial Registration Protocol registered on Prospero (CRD42020192823).
Topics: Cholecystectomy; Cholecystectomy, Laparoscopic; Humans; Pancreatitis
PubMed: 35306590
DOI: 10.1007/s00268-022-06501-4 -
Frontiers in Medicine 2021Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most...
Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most effective analgesic protocol. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the safety and efficacy of analgesics for pain relief in AP. A literature search was performed to identify all RCTs assessing analgesics in patients with AP. The primary outcome was the number of participants who needed rescue analgesia. Study quality was assessed using Jadad score. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CI) were analysed using a random-effects model. Twelve studies comprising 699 patients with AP (83% mild AP) were analysed. The tested analgesics significantly decreased the need for rescue analgesia (3 studies, OR.36, 95% CI 0.21 to 0.60) vs. placebo or conventional treatment. The analgesics also improved the pain score [Visual Analogue Scale (Δ-VAS)] at 24 h (WMD 18.46, 0.84 to 36.07) and by the 3rd to 7th days (WMD 11.57, 0.87 to 22.28). Opioids vs. non-opioids were associated with a decrease in the need for rescue analgesia (6 studies, OR 0.25, 95% CI 0.07 to 0.86, = 0.03) but without significance in pain score. In subgroup analyses, opioids were similar to non-steroidal anti-inflammatory drugs (NSAIDs) regarding the primary outcome (4 studies, OR 0.56, 95% CI 0.24 to 1.32, = 0.18). There were no significant differences in other clinical outcomes and rate of adverse events. Other studies, comparing epidural anaesthesia vs. patient-controlled analgesia and opioid (buprenorphine) vs. opioid (pethidine) did not show significant difference in primary outcome. Study quality issues significantly contributed to overall study heterogeneity. NSAIDs and opioids are equally effective in decreasing the need for rescue analgesia in patients with mild AP. The relative paucity of trials and high-quality data in this setting is notable and the optimal analgesic strategy for patients with moderately severe and severe AP still requires to be determined.
PubMed: 34977084
DOI: 10.3389/fmed.2021.782151 -
HPB : the Official Journal of the... Nov 2021Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adequate fluid resuscitation is paramount in the management of acute pancreatitis (AP). The aim of this study is to assess benefits and harms of fluid therapy protocols in patients with AP.
METHODS
MEDLINE, Embase, Science Citation Index and clinical trial registries were searched for randomised clinical trials published before May 2020, assessing types of fluids, routes and rates of administration.
RESULTS
A total 15 trials (1073 participants) were included. Age ranged from 38 to 73 years; follow-up period ranged from 0.5 to 6 months. Ringer lactate (RL) showed a reduced number of severe adverse events (SAE) when compared to normal saline (NS) (OR 0.48; 95%CI 0.29-0.81, p = 0.006); additionally, NS showed reduced SAE (RR 0.38; 95%IC 0.27-0.54, p < 0.001) and organ failure (RR 0.30; 95%CI 0.21-0.44, p < 0.001) in comparison with hydroxyethyl starch (HES). High fluid rate fluid infusion showed increased mortality (OR 2.88; 95%CI 1.41-5.88, p = 0.004), increased number of SAE (RR 1.42; 95%CI 1.04-1.93, p = 0.030) and higher incidence of sepsis (RR 2.80; 95%CI 1.51-5.19, p = 0.001) compared to moderate fluid rate infusion.
CONCLUSIONS
In patients with AP, RL should be preferred over NS and HES should not be recommended. Based on low-certainty evidence, moderate-rate fluid infusion should be preferred over high-rate infusion.
Topics: Child; Child, Preschool; Humans; Acute Disease; Fluid Therapy; Pancreatitis; Sepsis; Clinical Protocols
PubMed: 34325967
DOI: 10.1016/j.hpb.2021.06.426 -
The Cochrane Database of Systematic... Apr 2017In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure.
OBJECTIVES
To assess the effects of different pharmacological interventions in people with acute pancreatitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials.
SELECTION CRITERIA
We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model.
MAIN RESULTS
We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin plus ulinastatin, thymosin, ulinastatin, and inactive control. Apart from the comparison of antibiotics versus control, which included a large proportion of participants with necrotising pancreatitis, the remaining comparisons had only a small proportion of patients with this condition. Most trials included either only participants with severe acute pancreatitis or included a mixture of participants with mild acute pancreatitis and severe acute pancreatitis (75 trials). Overall, the risk of bias in trials was unclear or high for all but one of the trials.
SOURCE OF FUNDING
seven trials were not funded or funded by agencies without vested interest in results. Pharmaceutical companies partially or fully funded 21 trials. The source of funding was not available from the remaining trials.Since we considered short-term mortality as the most important outcome, we presented only these results in detail in the abstract. Sixty-seven studies including 6638 participants reported short-term mortality. There was no evidence of any differences in short-term mortality in any of the comparisons (very low-quality evidence). With regards to other primary outcomes, serious adverse events (number) were lower than control in participants taking lexipafant (rate ratio 0.67, 95% CI 0.46 to 0.96; N = 290; 1 study; very low-quality evidence), octreotide (rate ratio 0.74, 95% CI 0.60 to 0.89; N = 770; 5 studies; very low-quality evidence), somatostatin plus omeprazole (rate ratio 0.36, 95% CI 0.19 to 0.70; N = 140; 1 study; low-quality evidence), and somatostatin plus ulinastatin (rate ratio 0.30, 95% CI 0.15 to 0.60; N = 122; 1 study; low-quality evidence). The proportion of people with organ failure was lower in octreotide than control (OR 0.51, 95% CI 0.27 to 0.97; N = 430; 3 studies; very low-quality evidence). The proportion of people with sepsis was lower in lexipafant than control (OR 0.26, 95% CI 0.08 to 0.83; N = 290; 1 study; very low-quality evidence). There was no evidence of differences in any of the remaining comparisons in these outcomes or for any of the remaining primary outcomes (the proportion of participants experiencing at least one serious adverse event and the occurrence of infected pancreatic necrosis). None of the trials reported heath-related quality of life.
AUTHORS' CONCLUSIONS
Very low-quality evidence suggests that none of the pharmacological treatments studied decrease short-term mortality in people with acute pancreatitis. However, the confidence intervals were wide and consistent with an increase or decrease in short-term mortality due to the interventions. We did not find consistent clinical benefits with any intervention. Because of the limitations in the prognostic scoring systems and because damage to organs may occur in acute pancreatitis before they are clinically manifest, future trials should consider including pancreatitis of all severity but power the study to measure the differences in the subgroup of people with severe acute pancreatitis. It may be difficult to power the studies based on mortality. Future trials in participants with acute pancreatitis should consider other outcomes such as complications or health-related quality of life as primary outcomes. Such trials should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).
Topics: Acute Disease; Anti-Bacterial Agents; Antioxidants; Confidence Intervals; Gastrointestinal Agents; Humans; Pancreatitis; Pancreatitis, Acute Necrotizing; Probiotics; Randomized Controlled Trials as Topic
PubMed: 28431202
DOI: 10.1002/14651858.CD011384.pub2 -
JAMA Surgery Jun 2023The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves...
IMPORTANCE
The incidence of chronic pancreatitis is 5 to 12 per 100 000 adults in industrialized countries, and the incidence is increasing. Treatment is multimodal, and involves nutrition optimization, pain management, and when indicated, endoscopic and surgical intervention.
OBJECTIVES
To summarize the most current published evidence on etiology, diagnosis, and management of chronic pancreatitis and its associated complications.
EVIDENCE REVIEW
A literature search of Web of Science, Embase, Cochrane Library, and PubMed was conducted for publications between January 1, 1997, and July 30, 2022. Excluded from review were the following: case reports, editorials, study protocols, nonsystematic reviews, nonsurgical technical publications, studies pertaining to pharmacokinetics, drug efficacy, pilot studies, historical papers, correspondence, errata, animal and in vitro studies, and publications focused on pancreatic diseases other than chronic pancreatitis. Ultimately, the highest-level evidence publications were chosen for inclusion after analysis by 2 independent reviewers.
FINDINGS
A total of 75 publications were chosen for review. First-line imaging modalities for diagnosis of chronic pancreatitis included computed tomography and magnetic resonance imaging. More invasive techniques such as endoscopic ultrasonography allowed for tissue analysis, and endoscopic retrograde cholangiopancreatography provided access for dilation, sphincterotomy, and stenting. Nonsurgical options for pain control included behavior modification (smoking cessation, alcohol abstinence), celiac plexus block, splanchnicectomy, nonopioid pain medication, and opioids. Supplemental enzymes should be given to patients with exocrine insufficiency to avoid malnutrition. Surgery was superior to endoscopic interventions for long-term pain control, and early surgery (<3 years from symptom onset) had more superior outcomes than late surgery. Duodenal preserving strategies were preferred unless there was suspicion of cancer.
CONCLUSIONS AND RELEVANCE
Results of this systematic review suggest that patients with chronic pancreatitis had high rates of disability. Strategies to improve pain control through behavioral modification, endoscopic measures, and surgery must also accompany management of the sequalae of complications that arise from endocrine and exocrine insufficiency.
Topics: Humans; Pancreatitis, Chronic; Cholangiopancreatography, Endoscopic Retrograde; Pain; Pain Management; Endosonography
PubMed: 37074693
DOI: 10.1001/jamasurg.2023.0367