Background
Pegylated interferon (peginterferon) plus ribavirin is the recommended treatment for patients with chronic hepatitis C, but systematic assessment of the effect of this treatment compared ...with interferon plus ribavirin is needed.
Objectives
To systematically evaluate the benefits and harms of peginterferon plus ribavirin versus interferon plus ribavirin for patients with chronic hepatitis C.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index‐Expanded, and LILACS. We also searched conference s, journals, and grey literature. The last searches were conducted in September 2013.
Selection criteria
We included randomised clinical trials comparing peginterferon plus ribavirin versus interferon plus ribavirin with or without co‐intervention(s) (e.g., other antiviral drugs) for chronic hepatitis C. Quasi‐randomised and observational studies retrieved through the searches for randomised clinical trials were also considered for reports of harms. Our primary outcomes were liver‐related morbidity, all‐cause mortality, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. Our secondary outcome was sustained virological response in serum, that is, undetectable hepatitis C virus RNA in serum by sensitive tests six months after the end of treatment.
Data collection and analysis
Two review authors independently used a standardised data collection form. We meta‐analysed data with both fixed‐effect and random‐effects models. For each outcome, we calculated the odds ratio (OR) (for liver‐related morbidity or all‐cause mortality) or the risk ratio (RR) along with 95% confidence interval (CI) based on intention‐to‐treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risk of random errors (play of chance).
For each outcome, we calculated the RR with 95% CI based on intention‐to‐treat analysis. Effects of interventions on outcomes were assessed according to GRADE.
Main results
We included 27 randomised trials with 5938 participants. All trials had high risk of bias. We considered that the risk of bias did not impact on the quality of evidence for liver‐related mortality and adverse event outcomes, but it did for virological response. All trials compared peginterferon alpha‐2a or peginterferon alpha‐2b plus ribavirin versus interferon plus ribavirin for participants with chronic hepatitis C. Three trials administered co‐interventions (amantadine hydrochloride 200 mg daily to both intervention groups), and 24 trials were conducted without co‐interventions. The effect observed between the two intervention groups regarding liver‐related morbidity plus all‐cause mortality (5/907 (0.55%) versus 4/882 (0.45%) was imprecise: OR 1.14 ( 95% CI 0.38 to 3.42; five trials; low quality of evidence), as was the risk of adverse events leading to treatment discontinuation (332/2692 (12.3%) versus 409/2176 (18.8%); RR 0.86, 95% CI 0.68 to 1.09; 15 trials; low quality of evidence) or regarding adverse events leading to treatment discontinuation (332/2692 (12.3%) versus 409/2176 (18.8%); RR 0.86, 95% CI 0.66 to 1.12; 17 trials; low quality of evidence). However, peginterferon plus ribavirin versus interferon plus ribavirin significantly increased the risk of neutropenia (332/2202 (15.1%) versus 117/1653 (7.1%); RR 2.15, 95% CI 1.76 to 2.61; 13 trials), thrombocytopenia (65/1113 (5.8%) versus 23/1082 (2.1%); RR 2.63, 95% CI 1.68 to 4.11; 10 trials), arthralgia (517/1740 (29.7%) versus 282/1194 (23.6%); RR 1.19, 95% CI 1.05 to 1.35; four trials), injection site reaction (627/1168 (53.7%) versus 186/649 (28.7%); RR 1.71, 95% CI 1.50 to 1.93; four trials), and nausea (606/1784 (34.0%) versus 354/1239 (28.6%); RR 1.13, 95% CI 1.01 to 1.26; four trials). The most frequent adverse event was fatigue, which occurred in 57% of participants (2024/3608). No significant difference was noted between peginterferon plus ribavirin versus interferon plus ribavirin in terms of fatigue (1177/2062 (57.1%) versus 847/1546 (54.8%); RR 1.01, 95% CI 0.96 to 1.07; 12 trials). No significant differences were reported between the two treatment groups regarding anaemia, headache, rigours, myalgia, pyrexia, weight loss, asthenia, depression, insomnia, irritability, alopecia, pruritus, skin rash, thyroid malfunction, decreased appetite, or diarrhoea. We were unable to identify any data on quality of life. Peginterferon plus ribavirin versus interferon plus ribavirin seemed to significantly increase the number of participants achieving sustained virological response (1673/3300 participants (50.7%) versus 1081/2804 patients (36.7%); RR 1.39, 95% CI 1.25 to 1.56; I2 = 64%; 27 trials; very low quality of evidence). However, the risk of bias in the 13/27 (48.1%) trials reporting on this outcome was high and was considered only 'lower' in the remainder. Because the conventional meta‐analysis did not reach its required information size (n = 14,486 participants), we used trial sequential analysis to control for risks of random errors. Again, in this analysis, the estimated effect was statistically significant in favour of peginterferon. Subgroup analyses according to risk of bias, viral genotype, baseline viral load, past treatment history, and type of intervention yielded similarly significant results favouring peginterferon over interferon on the outcome of sustained virological response.
Authors' conclusions
Peginterferon plus ribavirin versus interferon plus ribavirin seems to significantly increase the proportion of patients with sustained virological response, as well as the risk of certain adverse events. However, we have insufficient evidence to recommend or reject peginterferon plus ribavirin for liver‐related morbidity plus all‐cause mortality compared with interferon plus ribavirin. The clinical consequences of achieved sustained virological response are unknown, as sustained virological response is still an unvalidated surrogate outcome. We found no evidence of the potential benefits on quality of life in patients with achieved sustained virological response. Further high‐quality research is likely to have an important impact on our confidence in the estimate of patient‐relevant outcomes and is likely to change our estimates.There is very low quality evidence that peginterferon plus ribavirin increases the proportion of patients with sustained virological response in comparison with interferon plus ribavirin. There is evidence that it also increases the risk of certain adverse events.
Background
A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. ...However, it is not established which of the two licensed peginterferon products, peginterferon alpha‐2a or peginterferon alpha‐2b, is the most effective and has a better safety profile.
Objectives
To systematically evaluate the benefits and harms of peginterferon alpha‐2a versus peginterferon alpha‐2b in head‐to‐head randomised clinical trials in patients with chronic hepatitis C.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and LILACS until October 2013. We also searched conference s, journals, and grey literature.
Selection criteria
We included randomised clinical trials comparing peginterferon alpha‐2a versus peginterferon alpha‐2b given with or without co‐intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi‐randomised studies and observational studies as identified by the searches were also considered for assessment of harms. Our primary outcomes were all‐cause mortality, liver‐related morbidity, serious adverse events, adverse events leading to treatment discontinuation, other adverse events, and quality of life. The secondary outcome was sustained virological response in the blood serum.
Data collection and analysis
Two authors independently used a standardised data collection form. We meta‐analysed data with both the fixed‐effect and the random‐effects models. For each outcome we calculated the relative risk (RR) with 95% confidence interval (CI) based on intention‐to‐treat analysis. We used domains of the trials to assess the risk of systematic errors (bias) and trial sequential analyses to assess the risks of random errors (play of chance). Intervention effects on the outcomes were assessed according to GRADE.
Main results
We included 17 randomised clinical trials which compared peginterferon alpha‐2a plus ribavirin versus peginterferon alpha‐2b plus ribavirin in 5847 patients. All trials had a high risk of bias. Very few trials reported data on very few patients for the patient‐relevant outcomes all‐cause mortality, liver‐related morbidity, serious adverse events, and quality of life. Accordingly, we were unable to conduct meta‐analyses on all‐cause mortality, liver‐related morbidity, and quality of life. Twelve trials reported on adverse events leading to discontinuation of treatment without clear evidence of a difference between the two peginterferons (197/2171 (9.1%) versus 311/3169 (9.9%); RR 0.84, 95% CI 0.57 to 1.22; I2 = 44%; low quality evidence). A trial sequential analysis showed that we could exclude a relative risk reduction of 20% or more on this outcome. Peginterferon alpha‐2a significantly increased the number of patients who achieved a sustained virological response in the blood serum compared with peginterferon alpha‐2b (1069/2099 (51%) versus 1327/3075 (43%); RR 1.12, 95% CI 1.06 to 1.18; I2= 0%, 12 trials; moderate quality evidence). Trial sequential analyses supported this result. Subgroup analyses based on risk of bias, viral genotype, and treatment history yielded similar results. Trial sequential analyses supported the results in patients with genotypes 1 and 4, but not in patients with genotypes 2 and 3.
Authors' conclusions
There is lack of evidence on patient‐important outcomes and paucity of evidence on adverse events. Moderate quality evidence suggests that peginterferon alpha‐2a is associated with a higher sustained virological response in serum than with peginterferon alpha‐2b. This finding may be affected by the high risk of bias of the included studies . The clinical consequences of peginterferon alpha‐2a versus peginterferon alpha‐2b are unknown, and we cannot translate an effect on sustained virological response into comparable clinical effects because sustained virological response is still an unvalidated surrogate outcome for patient‐important outcomes. The lack of evidence on patient‐important outcomes and the paucity of evidence on adverse events means that we are unable to draw any conclusions about the effects of one peginterferon over the other.
Background
Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are tests used in the diagnosis of common bile duct stones in patients suspected of having common bile ...duct stones prior to undergoing invasive treatment. There has been no systematic review of the accuracy of EUS and MRCP in the diagnosis of common bile duct stones using appropriate reference standards.
Objectives
To determine and compare the accuracy of EUS and MRCP for the diagnosis of common bile duct stones.
Search methods
We searched MEDLINE, EMBASE, Science Citation Index Expanded, BIOSIS, and Clinicaltrials.gov until September 2012. We searched the references of included studies to identify further studies and of systematic reviews identified from various databases (Database of s of Reviews of Effects (DARE), Health Technology Assessment (HTA), Medion, and ARIF (Aggressive Research Intelligence Facility)). We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively.
Selection criteria
We included studies that provided the number of true positives, false positives, false negatives, and true negatives for EUS or MRCP. We only accepted studies that confirmed the presence of common bile duct stones by extraction of the stones (irrespective of whether this was done by surgical or endoscopic methods) for a positive test, and absence of common bile duct stones by surgical or endoscopic negative exploration of the common bile duct or symptom free follow‐up for at least six months for a negative test, as the reference standard in people suspected of having common bile duct stones. We included participants with or without prior diagnosis of cholelithiasis; with or without symptoms and complications of common bile duct stones, with or without prior treatment for common bile duct stones; and before or after cholecystectomy. At least two authors independently screened s and selected studies for inclusion.
Data collection and analysis
Two authors independently collected the data from each study. We used the bivariate model to obtain pooled estimates of sensitivity and specificity.
Main results
We included a total of 18 studies involving 2366 participants (976 participants with common bile duct stones and 1390 participants without common bile duct stones). Eleven studies evaluated EUS alone, and five studies evaluated MRCP alone. Two studies evaluated both tests. Most studies included patients who were suspected of having common bile duct stones based on abnormal liver function tests; abnormal transabdominal ultrasound; symptoms such as obstructive jaundice, cholangitis, or pancreatitis; or a combination of the above. The proportion of participants who had undergone cholecystectomy varied across studies. Not one of the studies was of high methodological quality. For EUS, the sensitivities ranged between 0.75 and 1.00 and the specificities ranged between 0.85 and 1.00. The summary sensitivity (95% confidence interval (CI)) and specificity (95% CI) of the 13 studies that evaluated EUS (1537 participants; 686 cases and 851 participants without common bile duct stones) were 0.95 (95% CI 0.91 to 0.97) and 0.97 (95% CI 0.94 to 0.99). For MRCP, the sensitivities ranged between 0.77 and 1.00 and the specificities ranged between 0.73 and 0.99. The summary sensitivity and specificity of the seven studies that evaluated MRCP (996 participants; 361 cases and 635 participants without common bile duct stones) were 0.93 (95% CI 0.87 to 0.96) and 0.96 (95% CI 0.90 to 0.98). There was no evidence of a difference in sensitivity or specificity between EUS and MRCP (P value = 0.5). From the included studies, at the median pre‐test probability of common bile duct stones of 41% the post‐test probabilities (with 95% CI) associated with positive and negative EUS test results were 0.96 (95% CI 0.92 to 0.98) and 0.03 (95% CI 0.02 to 0.06). At the same pre‐test probability, the post‐test probabilities associated with positive and negative MRCP test results were 0.94 (95% CI 0.87 to 0.97) and 0.05 (95% CI 0.03 to 0.09).
Authors' conclusions
Both EUS and MRCP have high diagnostic accuracy for detection of common bile duct stones. People with positive EUS or MRCP should undergo endoscopic or surgical extraction of common bile duct stones and those with negative EUS or MRCP do not need further invasive tests. However, if the symptoms persist, further investigations will be indicated. The two tests are similar in terms of diagnostic accuracy and the choice of which test to use will be informed by availability and contra‐indications to each test. However, it should be noted that the results are based on studies of poor methodological quality and so the results should be interpreted with caution. Further studies that are of high methodological quality are necessary to determine the diagnostic accuracy of EUS and MRCP for the diagnosis of common bile duct stones.
Given the emerging role of endoscopic procedures in the treatment of obesity and rapid changes in endoscopic technologies and techniques, this review considers the current state of endoscopic ...management of obesity. Endoluminal interventions performed entirely through the GI tract by using flexible endoscopy offer the potential for an ambulatory weight loss procedure that may be safer and more cost- effective compared with current surgical approaches. Endoscopic techniques attempt to mimic the anatomic features of bariatric surgery. Accordingly, there are two main endoscopic weight loss modalities - restrictive and malabsorptive. Restrictive procedures act to decrease gastric volume by space-occupying prosthesis and/or by suturing or stapling devices, while malabsorptive procedures tend to create malabsorption by preventing food contact with the duodenum and proximal jejunum. The former include intragastric balloon treatment, endoluminal vertical gastroplasty, transoral gastroplasty and transoral endoscopic restrictive implant system, while the latter include duodenojejunal bypass sleeve. Gastroduodenojejunal bypass sleeve is a combination of both procedures. Except for intragastric balloon, all mentioned procedures are rather new, tested on a small number of human subjects, with a high rate of success, but with limited knowledge on safety and long-term efficacy. The role of gastric electrical stimulation and intragastric injections of botulinum toxin in obesity treatment is also considered as is the role of minimally invasive bariatric endoscopic interventions.
Obesogens – new global health problem? Ćurić, Melany; Klobučar Majanović, Sanja; Detel, Dijana ...
Periodicum biologorum,
07/2022, Volume:
123, Issue:
3-4
Journal Article
Open access
Obesity is a serious global public health problem. It is a complex disease caused by a combination of several factors including overeating and a sedentary lifestyle, genetic susceptibility and ...environmental factors. Substantial scientific evidence indicates that increase in obesity prevalence correlates with increase in production and human exposure to environmental chemicals, suggesting that a long list of chemical compounds that can be found all around us may play a role in the etiology of obesity.Endocrine disrupting compounds (EDCs) are chemicals that can interfere with the function of endocrine system. A subclass of EDCs that can disrupt a great number of metabolic processes including normal development of adipose tissue and balance of lipid metabolism thus leading to obesity are called obesogens. They can be found in electronics, plastics, furniture, clothes, cosmetics and also in the air, water and food that people consume. Persistent organophosphate pesticides, flame retardants, nicotine and plastics have all been linked to obesity particularly if exposure occurs during early life (in utero, newborns). Early development is the most vulnerable period for obesogen exposure leading to epigenetic changes that persist throughout life.Current knowledge on obesogens is probably just „the tip of the iceberg“ and future research is needed as well as increasing public awareness of this problem and its implications to human health. It is important to establish control over obesogens and try to prevent or at least limit the exposure of people, especially children and pregnant women, to these dangerous and harmful chemical compounds.
What’s New in Diagnosing Diverticular Disease ŠTIMAC, Davor; Nardone, Gerardo; Mazzari, Andrea ...
Journal of gastrointestinal and liver diseases : JGLD,
2019-Dec-19, Volume:
28
Journal Article
Open access
In this session different issues for the diagnosis of diverticular disease (DD) were considered including “Biomarkers”, “Computer tomography”, “Ultrasonography in detecting acute diverticulitis”, ...“Endoscopy” and “The DICA classification: a new predictive tool in managing diverticular disease”. Most patients affected by DD suffer from recurrent attacks of abdominal pain without evidence of an active inflammatory process, causing a difficult differential diagnosis with other intestinal conditions. Several biomarkers, serological, fecal, urinary and genetic were considered, but recent studies confirmed that only CRP and fecal calprotectin are matching with the criteria for an ideal biomarker for DD. Colonoscopy still remains the gold standard for the diagnosis of DD, playing a key role in many clinical settings, such as colonic diverticular bleeding, or to differentiate inflammatory bowel disease (IBD) and segmental colitis associated with diverticulosis (SCAD); Moreover, in 2015 has been developed the DICA (Diverticular Inflammation and Complication Assessment) endoscopic classification that considers 10 different parameters, each one with a score, and the sum of items scores represents the severity of the disease; in this way the endoscopic exam would be able to predict the outcome of DD for each patient. On the other hand, computer tomography (CT) is the gold standard for acute diverticulitis (AD) with an excellent sensitivity and specificity; recently, metanalysis of prospective studies have shown that intestinal ultrasonography (IUS) and CT have the same sensitivity for the diagnosis of an AD and the advantage is that IUS is less expensive, non-invasive and easily accessible.
Colorectal cancer is a malignant neoplasm which has an increasing incidence and represents a global public health problem. The majority of patients are diagnosed after the age of 50, and the risk of ...developing it over lifetime is 5%. Development of preventive, diagnostic and treatment methods has resulted in a significant reduction in mortality and other negative clinical outcomes. Precisely because of the efficient method of prevention and early detection of this disease, numerous countries, including Croatia, have organized national colorectal cancer screening and monitoring programs. However, these programs are primarily organized for the population with the usual, i.e. average risk of developing colorectal cancer. High-risk groups include persons with endoscopically detected and removed colon polyps, persons surgically treated for colon cancer, persons with a positive family history of colorectal cancer, persons with inflammatory bowel diseases, individuals and families with hereditary disorders or genetic mutations that increase the risk of this disease several fold, persons with acromegaly, and patients who have undergone ureterosigmoidostomy. Recommendations for the detection and monitoring of high-risk groups are often not defined clearly, and some of the existing ones are based mostly on scarce scientific evidence. It is commonly accepted that screening in high-risk groups should start at an earlier age, with shorter intervals between follow-ups. The basic diagnostic method for screening and monitoring in these patient groups is endoscopic monitoring, or colonoscopy. The aim of this review paper is to present the characteristics of the abovementioned risk groups and provide clear screening recommendations.
To determine the prevalence of American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) classification criteria among systemic lupus erythematosus (SLE) ...patients; to determine disease activity and severity; and to investigate the correlation of classification criteria with disease activity, and of disease activity and damage index with disease duration.
We performed a cross-sectional study on 110 SLE patients from the Division of Rheumatology and Clinical Immunology, University Hospital Centre Rijeka, Croatia in the period from September to December 2013 and determined disease duration and the total number of ACR and SLICC classification criteria. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) index and organ damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index.
The number of SLICC classification criteria met per patient was significantly higher than the number of ACR criteria (7 IQR 6-8 vs 5 IQR 4-6, P < 0.001). Moderate correlations were detected between the number of SLICC classification criteria and disease activity index, both in case of active (r=0.48, P=0.003) and inactive disease (r=0.43, P < 0.001). We neither found a correlation between the number of ACR criteria and disease activity nor between disease activity and disease duration. However, there was a good correlation between SLICC/ACR damage index and disease duration (r=0.63, P < 0.001).
New SLICC classification criteria correlate with disease activity because they capture more manifestations also included in the SLEDAI index. Patients with longer disease duration had a larger damage index score.
Background & Aims Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in ...patients with mildly to moderately active CD. Methods We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L–coated oral mesalamine (4.5 g/day). Results The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, −4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups. Conclusions Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L–coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen.
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