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Einstein (Sao Paulo, Brazil) 2014In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when... (Review)
Review
In HIV-seropositive individuals, the incidence of acute pancreatitis may achieve 40% per year, higher than the 2% found in the general population. Since 1996, when combined antiretroviral therapy, known as HAART (highly active antiretroviral therapy), was introduced, a broad spectrum of harmful factors to the pancreas, such as opportunistic infections and drugs used for chemoprophylaxis, dropped considerably. Nucleotide analogues and metabolic abnormalities, hepatic steatosis and lactic acidosis have emerged as new conditions that can affect the pancreas. To evaluate the role of antiretroviral drugs to treat HIV/AIDS in a scenario of high incidence of acute pancreatitis in this population, a systematic review was performed, including original articles, case reports and case series studies, whose targets were HIV-seropositive patients that developed acute pancreatitis after exposure to any antiretroviral drugs. This association was confirmed after exclusion of other possible etiologies and/or a recurrent episode of acute pancreatitis after re-exposure to the suspected drug. Zidovudine, efavirenz, and protease inhibitors are thought to lead to acute pancreatitis secondary to hyperlipidemia. Nucleotide reverse transcriptase inhibitors, despite being powerful inhibitors of viral replication, induce a wide spectrum of side effects, including myelotoxicity and acute pancreatitis. Didanosine, zalcitabine and stavudine have been reported as causes of acute and chronic pancreatitis. They pose a high risk with cumulative doses. Didanosine with hydroxyurea, alcohol or pentamidine are additional risk factors, leading to lethal pancreatitis, which is not a frequent event. In addition, other drugs used for prophylaxis of AIDS-related opportunistic diseases, such as sulfamethoxazole-trimethoprim and pentamidine, can produce necrotizing pancreatitis. Despite comorbidities that can lead to pancreatic involvement in the HIV/AIDS population, antiretroviral drug-induced pancreatitis should always be considered in the diagnosis of patients with abdominal pain and elevated pancreatic enzymes.
Topics: Acquired Immunodeficiency Syndrome; Acute Disease; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Comorbidity; Female; Humans; Male; Pancreatitis; Risk Factors
PubMed: 24728257
DOI: 10.1590/s1679-45082014rw2561 -
Health Technology Assessment... Dec 2013Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of... (Review)
Review
Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model.
BACKGROUND
Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales.
OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF.
DATA SOURCES
Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched.
REVIEW METHODS
A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed.
RESULTS
Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second percentage predicted (FEV1%). It was not possible to draw any firm conclusions as to the relative efficacy of colistimethate sodium DPI compared with tobramycin DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the incremental discounted lifetime cost of tobramycin DPI compared with nebulised tobramycin, it highly unlikely that tobramycin DPI has an incremental cost-effectiveness ratio that is better than £30,000 per QALY gained.
LIMITATION
The uncertainty surrounding the short-term evidence base inevitably results in uncertainty surrounding the long-term clinical effectiveness and cost-effectiveness of colistimethate sodium DPI.
CONCLUSIONS
Both DPI formulations have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%. The results of these trials should be interpreted with caution owing to the means by which the results were analysed, the length of follow-up, and concerns about the ability of FEV1% to accurately represent changes in lung health. Although the increase in QALYs is expected to be lower with colistimethate sodium DPI than with nebulised tobramycin, a price for this intervention had not been agreed at the time of the assessment. Depending on the price of colistimethate sodium DPI, this results either in a situation whereby colistimethate sodium DPI is dominated by nebulised tobramycin or in one whereby the incremental cost-effectiveness of nebulised tobramycin compared with colistimethate sodium DPI is in the range of £24,000-277,000 per QALY gained. The economic analysis also suggests that, given its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of < £30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess the longer-term (≥ 12 months) efficacy of colistimethate sodium DPI and tobramycin DPI in comparison with nebulised treatments would be beneficial. Such a study should include the direct assessment of HRQoL using a relevant preference-based instrument. Future studies should ensure that the European Medicines Agency guidelines are adhered to. In addition, high-quality research concerning the relationship between forced expiratory volume in first second % (FEV1%) predicted or other measures of lung function and survival/health-related quality of life (HRQoL) would be useful.
STUDY REGISTRATION
PROSPERO CRD42011001350.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Administration, Inhalation; Child; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Disease Progression; Humans; Outcome Assessment, Health Care; Pseudomonas Infections; Pseudomonas aeruginosa; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Therapeutic Equivalency; Tobramycin; United Kingdom
PubMed: 24290164
DOI: 10.3310/hta17560 -
The Cochrane Database of Systematic... Apr 2013Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery; however, their use is controversial.
OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.
SEARCH METHODS
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE, EMBASE and Science Citation Index Expanded to February 2013.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed a per protocol analysis.
MAIN RESULTS
We identified 21 trials (19 trials of high risk of bias) involving 2348 people. There was no significant difference in the perioperative mortality (RR 0.80; 95% CI 0.56 to 1.16; n = 2210) or the number of people with drug-related adverse effects between the two groups (RR 2.09; 95% CI 0.83 to 5.24; n = 1199). Quality of life was not reported in any of the trials. The overall number of participants with postoperative complications was significantly lower in the somatostatin analogue group (RR 0.70; 95% CI 0.61 to 0.80; n = 1903) but there was no significant difference in the re-operation rate (RR 1.26; 95% CI 0.58 to 2.70; n = 687) or hospital stay (MD -1.29 days; 95% CI -2.60 to 0.03; n = 1314) between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.66; 95% CI 0.55 to 0.79; n = 2206). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no significant difference between the two groups (RR 0.69; 95% CI 0.38 to 1.28; n = 292).
AUTHORS' CONCLUSIONS
Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.
Topics: Gastrointestinal Agents; Humans; Length of Stay; Octreotide; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Publication Bias; Randomized Controlled Trials as Topic; Reoperation; Sepsis; Somatostatin
PubMed: 23633353
DOI: 10.1002/14651858.CD008370.pub3 -
HPB : the Official Journal of the... Nov 2012Currently, laparoscopic distal pancreatectomy (LDP) is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Currently, laparoscopic distal pancreatectomy (LDP) is regarded as a safe and effective surgical approach for lesions in the body and tail of the pancreas. This review compares outcomes of the laparoscopic technique with those of open distal pancreatectomy (ODP) and assesses the efficacy, safety and feasibility of each type of procedure.
METHODS
Comparative studies published between January 1996 and April 2012 were included. Studies were selected based on specific inclusion and exclusion criteria. Evaluated endpoints were operative outcomes, postoperative recovery and postoperative complications.
RESULTS
Fifteen non-randomized comparative studies that recruited a total of 1456 patients were analysed. Rates of conversion from LDP to open surgery ranged from 0% to 30%. Patients undergoing LDP had less intraoperative blood loss [weighted mean difference (WMD) -263.36.59 ml, 95% confidence interval (CI) -330.48 to -196.23 ml], fewer blood transfusions [odds ratio (OR) 0.28, 95% CI 0.11-0.76], shorter hospital stay (WMD -4.98 days, 95% CI -7.04 to -2.92 days), a higher rate of splenic preservation (OR 2.98, 95% CI 2.18-3.91), earlier oral intake (WMD -2.63 days, 95% CI -4.23 to 1.03 days) and fewer surgical site infections (OR 0.37, 95% CI 0.18-0.75). However, there were no differences between the two approaches with regard to operation time, time to first flatus and the occurrence of pancreatic fistula and other postoperative complications.
CONCLUSIONS
Laparoscopic resection results in improved operative and postoperative outcomes compared with open surgery according to the results of the present meta-analyses. It may be a safe and feasible option for patients with lesions in the body and tail of the pancreas. However, randomized controlled trials should be undertaken to confirm the relevance of these early findings.
Topics: Chi-Square Distribution; Humans; Laparoscopy; Odds Ratio; Pancreatectomy; Pancreatic Diseases; Postoperative Complications; Recovery of Function; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 23043660
DOI: 10.1111/j.1477-2574.2012.00531.x -
World Journal of Gastroenterology Feb 2012Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts....
Pancreatic tuberculosis (TB) is a relatively rare disease that can mimic carcinoma, lymphoma, cystic neoplasia, retroperitoneal tumors, pancreatitis or pseudocysts. Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass. The patient was diagnosed with pancreatic TB and acquired immunodeficiency syndrome, and was treated with antituberculous drugs and percutaneous catheter drainage without a laparotomy. The clinical presentation, radiographic investigation and management of pancreatic TB are summarized in this paper to emphasize the importance of considering this rare disease in the differential diagnosis of pancreatic masses concomitant with human immunodeficiency virus infection. I also emphasize the need for both histopathological and microbiological diagnosis via fine-needle aspiration.
Topics: Adult; Female; Humans; Acquired Immunodeficiency Syndrome; Comorbidity; Diagnosis, Differential; Fatal Outcome; Pancreas; Pancreatic Diseases; Tuberculosis; Ultrasonography
PubMed: 22363146
DOI: 10.3748/wjg.v18.i7.720 -
The Cochrane Database of Systematic... May 2010Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection.
OBJECTIVES
To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis.
SEARCH STRATEGY
Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis.
DATA COLLECTION AND ANALYSIS
Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem).
MAIN RESULTS
Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84).
AUTHORS' CONCLUSIONS
No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.
Topics: Acute Disease; Antibiotic Prophylaxis; Bacterial Infections; Humans; Necrosis; Pancreas; Pancreatitis; Pancreatitis, Acute Necrotizing; Randomized Controlled Trials as Topic; Superinfection
PubMed: 20464721
DOI: 10.1002/14651858.CD002941.pub3