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Journal of Pain Research 2018Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been... (Review)
Review
Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000-December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%-91.5%), with high heterogeneity ( test: <0.001; 2=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%-18.0% and 6.0%-8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.
PubMed: 30323651
DOI: 10.2147/JPR.S167994 -
Critical Care (London, England) Jan 2018Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes.
METHODS
We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored.
RESULTS
Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to 0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48 to 0.72, p = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03).
CONCLUSIONS
Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.
Topics: Clostridium Infections; Critical Care; Duodenal Ulcer; Enteral Nutrition; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Peptic Ulcer; Respiration, Artificial; Risk Management; Time Factors
PubMed: 29374489
DOI: 10.1186/s13054-017-1937-1 -
Critical Care (London, England) May 2016The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relative efficacy and safety of proton pump inhibitors (PPIs) compared to histamine-2-receptor antagonists (H2RAs) should guide their use in reducing bleeding risk in the critically ill.
METHODS
We searched the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015 without language or publication date restrictions. Only randomized controlled trials (RCTs) of PPIs vs H2RAs for stress ulcer prophylaxis in critically ill adults for clinically important bleeding, overt gastrointestinal (GI) bleeding, nosocomial pneumonia, mortality, ICU length of stay and Clostridium difficile infection were included. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess our confidence in the evidence for each outcome.
RESULTS
In 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important GI bleeding (RR 0.39; 95 % CI 0.21, 0.71; P = 0.002; I (2) = 0 %, moderate confidence) and overt GI bleeding (RR 0.48; 95 % CI 0.34, 0.66; P < 0.0001; I (2) = 3 %, moderate confidence). PPI use did not significantly affect risk of pneumonia (RR 1.12; 95 % CI 0.86, 1.46; P = 0.39; I (2) = 2 %, low confidence), mortality (RR 1.05; 95 % CI 0.87, 1.27; P = 0.61; I (2) = 0 %, moderate confidence), or ICU length of stay (mean difference (MD), -0.38 days; 95 % CI -1.49, 0.74; P = 0.51; I (2) = 30 %, low confidence). No RCT reported Clostridium difficile infection.
CONCLUSIONS
PPIs were superior to H2RAs in preventing clinically important and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality. Their impact on Clostridium difficile infection is yet to be determined.
Topics: Duodenal Ulcer; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Peptic Ulcer; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Stomach Ulcer
PubMed: 27142116
DOI: 10.1186/s13054-016-1305-6 -
The Cochrane Database of Systematic... Apr 2016Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peptic ulcer disease is the cause of dyspepsia in about 10% of people. Ninety-five percent of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H. pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. This is an update of Ford AC, Delaney B, Forman D, Moayyedi P. Eradication therapy for peptic ulcer disease in Helicobacter pylori-positive patients. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003840. DOI: 10.1002/14651858.CD003840.pub4.
OBJECTIVES
To assess the proportion of peptic ulcers healed and the proportion of participants who remained free from relapse with eradication therapy against placebo or other pharmacological therapies in H. pylori-positive people.To assess the proportion of participants that achieved complete relief of symptoms and improvement in quality of life scores.To compare the incidence of adverse effects/drop-outs (total number for each drug) associated with the different treatments.To assess the proportion of participants in whom successful eradication was achieved.
SEARCH METHODS
In this update, we identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (1950 to March 2016) and Ovid EMBASE (1980 to March 2016). To identify further relevant trials, we handsearched reference lists from trials selected by electronic searching, and published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology). The search was last updated in March 2016. We contacted members of Cochrane Upper GI and Pancreatic Diseases, and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials.
SELECTION CRITERIA
We analysed randomised controlled trials of short- and long-term treatment of peptic ulcer disease in H. pylori-positive adults. Participants received at least one week of H. pylori eradication compared with ulcer healing drug, placebo or no treatment. Trials were included if they reported assessment from two weeks onwards.
DATA COLLECTION AND ANALYSIS
We collected data on ulcer healing, recurrence, relief of symptoms and adverse effects. We calculated the risk ratio (RR) with 95% confidence intervals (CI) using both fixed-effect and random-effects models with Review Manager software (RevMan 5.3) based on intention-to-treat analysis as far as possible.
MAIN RESULTS
A total of 55 trials were included for one or more outcomes for this review.In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 participants, RR of ulcer persisting = 0.66, 95% confidence interval (CI) 0.58 to 0.76; 381/2286 (adjusted proportion: 12.4%) in eradication therapy plus UHD versus 304/1624 (18.7%) in UHD; low quality evidence) and no treatment (two trials, 207 participants, RR 0.37, 95% CI 0.26 to 0.53; 30/125 (adjusted proportion: 21.7%) in eradication therapy versus 48/82 (58.5%) in no treatment; low quality evidence).In gastric ulcer healing, the differences were imprecise between eradication therapy and UHD (15 trials, 1974 participants, RR 1.23, 95% CI 0.90 to 1.68; 220/1192 (adjusted proportion: 16.0%) in eradication therapy plus UHD versus 102/782 (13.0%) in UHD; very low quality evidence). In preventing duodenal ulcer recurrence the differences were imprecise between maintenance therapy with H.pylori eradication therapy and maintenance therapy with UHD (four trials, 319 participants, RR of ulcer recurring 0.73; 95% CI 0.42 to 1.25; 19/159 (adjusted proportion: 11.9%) in eradication therapy versus 26/160 (16.3%) in UHD; very low quality evidence), but eradication therapy was superior to no treatment (27 trials 2509 participants, RR 0.20, 95% CI 0.15 to 0.26; 215/1501 (adjusted proportion: 12.9%) in eradication therapy versus 649/1008 (64.4%) in no treatment; very low quality evidence).In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (12 trials, 1476 participants, RR 0.31, 95% CI 0.22 to 0.45; 116/697 (adjusted proportion: 16.3%) in eradication therapy versus 356/679 (52.4%) in no treatment; very low quality evidence). None of the trials reported proportion of people with gastric ulcer not healed after initial therapy between H.pylori eradication therapy and no active treatment or the proportion of people with recurrent gastric ulcer or peptic ulcers during maintenance therapy between H.pylori eradication therapy and ulcer healing drug therapy.
AUTHORS' CONCLUSIONS
Adding a one to two-week course of H. pylori eradication therapy is an effective treatment for people with H. pylori-positive duodenal ulcer when compared to ulcer healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer healing drug. However, confidence intervals were wide and significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment, and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out.
Topics: Adult; Anti-Bacterial Agents; Anti-Ulcer Agents; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Randomized Controlled Trials as Topic; Stomach Ulcer
PubMed: 27092708
DOI: 10.1002/14651858.CD003840.pub5 -
Journal of Infection in Developing... Jul 2015The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and... (Meta-Analysis)
Meta-Analysis Review
The varieties of infections caused by Helicobacter pylori may be due to differences in bacterial genotypes and virulence factors as well as environmental and host-related factors. This study aimed to investigate the prevalence of cagA and vacA genes among H. pylori-infected patients in Iran and analyze their relevance to the disease status between two clinical groups via a meta-analysis method. Different databases including PubMed, ISI, Scopus, SID, Magiran, Science Direct, and Medlib were investigated, and 23 relevant articles from the period between 2001 and 2012 were finally analyzed. The relevant data obtained from these papers were analyzed by a random-effects model. Data were analyzed using R software and STATA. The prevalence of cagA and vacA genes among H. pylori-infected patients was 70% (95% CI, 64-75) and 41% (95% CI, 24.3-57.7), respectively. The prevalence of duodenal ulcers, peptic ulcers, and gastritis among cagA+ individuals was 53% (95% CI, 20-86), 65% (95% CI, 34-97), and 71% (95% CI, 59-84), respectively. Odds ratio (OR) between cagA-positive compared with cagA-negative patients showed a 1.89 (95% CI, 1.38-2.57) risk of ulcers. In conclusion, the frequency of cagA gene among H. pylori strains is elevated in Iran and it seems to be more frequently associated with gastritis. Therefore, any information about cagA and vacA prevalence among different H. pylori-infected clinical groups in the country can help public health authorities to plan preventive policies to reduce the prevalence of diseases associated with H. pylori infection.
Topics: Antigens, Bacterial; Bacterial Proteins; Gastritis; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Iran; Peptic Ulcer; Prevalence
PubMed: 26230117
DOI: 10.3855/jidc.5970 -
Canadian Journal of Gastroenterology &... Nov 2014Peptic ulcer rebleeding (PUR) usually occurs within three days following endoscopic hemostasis. However, recent data have increasingly suggested delayed rebleeding. (Review)
Review
BACKGROUND
Peptic ulcer rebleeding (PUR) usually occurs within three days following endoscopic hemostasis. However, recent data have increasingly suggested delayed rebleeding.
OBJECTIVE
To better characterize the timing of PUR (Forrest Ia to IIb) following initially successful endoscopic hemostasis.
METHODS
An exhaustive literature search (1989 to 2013), with cross-referencing, was performed to identify pertinent randomized controlled trial (RCT) arms. Patients receiving high-dose proton pump inhibitor (PPI) infusion following successful modern-day endoscopic hemostasis were included. A sensitivity analysis included any patients receiving PPI doses >40 mg daily. The main outcome measure was 30-day rebleeding, while weighted mean averages at t = three, seven, 14 and 28 to 30 days are also reported.
RESULTS
Of 756 citations, six RCTs were included (561 patients; 58.5% to 89.5% male; 55.3 to 67.5 years of age). Among patients receiving high-dose PPI (five RCTs [393 patients]), 11.5% (95% CI 8.4% to 14.7%) experienced rebleeding, 55.6% (95% CI 41.1% to 70.1%) rebled within three days, 20% (95% CI 8.3% to 31.7%) between four and seven days, 17.8% (95% CI 6.6% to 28.9%) at eight to 14 days, and 6.7% (95% CI 0% to 14%) at 15 to 28 to 30 days. Using the relaxed lower PPI dosing threshold, similar respective rates were 14.4% (95% CI 11.5% to 17.3%) overall, with interval rates of 39.5% (95% CI 28.9% to 50.15%), 34.6% (95% CI 24.2% to 44.9%), 19.7% (95% CI 11% to 28.4%) and 6.2% (95% CI 0.95% to 11.5%). Qualitative review of patient characteristics, limited by small sample size, possible bias and study heterogeneity, suggested increased patient comorbidity and postendoscopic use of lower PPI dosing may predict delayed rebleeding.
CONCLUSION
In patients with high-risk PUR undergoing successful endoscopic hemostasis, most rebled within three days, with many experiencing later rebleeding. Additional research is needed to better predict such an outcome.
Topics: Adult; Aged; Aged, 80 and over; Duodenal Ulcer; Female; Hemostasis, Endoscopic; Humans; Male; Middle Aged; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors; Recurrence; Risk Factors; Time Factors
PubMed: 25390616
DOI: 10.1155/2014/324967 -
World Journal of Gastroenterology Oct 2014Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori (H. pylori) infection associated duodenal... (Meta-Analysis)
Meta-Analysis Review
Peptic ulcer disease continues to be issue especially due to its high prevalence in the developing world. Helicobacter pylori (H. pylori) infection associated duodenal ulcers should undergo eradication therapy. There are many regimens offered for H. pylori eradication which include triple, quadruple, or sequential therapy regimens. The central aim of this systematic review is to evaluate the evidence for H. pylori therapy from a meta-analytical outlook. The consequence of the dose, type of proton-pump inhibitor, and the length of the treatment will be debated. The most important risk factor for eradication failure is resistance to clarithromycin and metronidazole.
Topics: Anti-Bacterial Agents; Chi-Square Distribution; Drug Administration Schedule; Drug Resistance, Bacterial; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Odds Ratio; Peptic Ulcer; Proton Pump Inhibitors; Risk Factors; Treatment Outcome
PubMed: 25356018
DOI: 10.3748/wjg.v20.i40.14527 -
The Cochrane Database of Systematic... Oct 2014Endoscopic therapy reduces the rebleeding rate and the need for surgery in patients with bleeding peptic ulcers. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endoscopic therapy reduces the rebleeding rate and the need for surgery in patients with bleeding peptic ulcers.
OBJECTIVES
To determine whether a second procedure improves haemostatic efficacy or patient outcomes or both after epinephrine injection in adults with high-risk bleeding ulcers.
SEARCH METHODS
For our update in 2014, we searched the following versions of these databases, limited from June 2009 to May 2014: Ovid MEDLINE(R) 1946 to May Week 2 2014; Ovid MEDLINE(R) Daily Update May 22, 2014; Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations May 22, 2014 (Appendix 1); Evidence-Based Medicine (EBM) Reviews-the Cochrane Central Register of Controlled Trials (CENTRAL) April 2014 (Appendix 2); and EMBASE 1980 to Week 20 2014 (Appendix 3).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing epinephrine alone versus epinephrine plus a second method. Populations consisted of patients with high-risk bleeding peptic ulcers, that is, patients with haemorrhage from peptic ulcer disease (gastric or duodenal) with major stigmata of bleeding as defined by Forrest classification Ia (spurting haemorrhage), Ib (oozing haemorrhage), IIa (non-bleeding visible vessel) and IIb (adherent clot) (Forrest Ia-Ib-IIa-IIb).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by The Cochrane Collaboration. Meta-analysis was undertaken using a random-effects model; risk ratios (RRs) with 95% confidence intervals (CIs) are presented for dichotomous data.
MAIN RESULTS
Nineteen studies of 2033 initially randomly assigned participants were included, of which 11 used a second injected agent, five used a mechanical method (haemoclips) and three employed thermal methods.The risk of further bleeding after initial haemostasis was lower in the combination therapy groups than in the epinephrine alone group, regardless of which second procedure was applied (RR 0.53, 95% CI 0.35 to 0.81). Adding any second procedure significantly reduced the overall bleeding rate (persistent and recurrent bleeding) (RR 0.57, 95% CI 0.43 to 0.76) and the need for emergency surgery (RR 0.68, 95% CI 0.50 to 0.93). Mortality rates were not significantly different when either method was applied.Rebleeding in the 10 studies that scheduled a reendoscopy showed no difference between epinephrine and combined therapy; without second-look endoscopy, a statistically significant difference was observed between epinephrine and epinephrine and any second endoscopic method, with fewer participants rebleeding in the combined therapy group (nine studies) (RR 0.32, 95% CI 0.21 to 0.48).For ulcers of the Forrest Ia or Ib type (oozing or spurting), the addition of a second therapy significantly reduced the rebleeding rate (RR 0.66, 95% CI 0.49 to 0.88); this difference was not seen for type IIa (visible vessel) or type IIb (adherent clot) ulcers. Few procedure-related adverse effects were reported, and this finding was not statistically significantly different between groups. Few adverse events occurred, and no statistically significant difference was noted between groups.The addition of a second injected method reduced recurrent and persistent rebleeding rates and surgery rates in the combination therapy group, but these findings were not statistically significantly different. Significantly fewer participants died in the combined therapy group (RR 0.50, 95% CI 0.25 to 1.00).Epinephrine and a second mechanical method decreased recurrent and persistent bleeding (RR 0.31, 95% CI 0.18 to 0.54) and the need for emergency surgery (RR 0.20, 95% CI 0.06 to 0.62) but did not affect mortality rates.Epinephrine plus thermal methods decreased the rebleeding rate (RR 0.49, 95% CI 0.30 to 0.78) and the surgery rate (RR 0.20, 95% CI 0.06 to 0.62) but did not affect the mortality rate.Our risk of bias estimates show that risk of bias was low, as, although the type of study did not allow a double-blind trial, rebleeding, surgery and mortality were not dependent on subjective observation. Although some studies had limitations in their design or implementation, most were clear about important quality criteria, including randomisation and allocation concealment, sequence generation and blinding.
AUTHORS' CONCLUSIONS
Additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer. The main adverse events include risk of perforation and gastric wall necrosis, the rates of which were low in our included studies and favoured neither epinephrine therapy nor combination therapy. The main conclusion is that combined therapy seems to work better than epinephrine alone. However, we cannot conclude that a particular form of treatment is equal or superior to another.
Topics: Adult; Combined Modality Therapy; Epinephrine; Hemostasis, Endoscopic; Humans; Peptic Ulcer Hemorrhage; Randomized Controlled Trials as Topic; Secondary Prevention; Vasoconstrictor Agents
PubMed: 25308912
DOI: 10.1002/14651858.CD005584.pub3