Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial.

OBJECTIVE--To investigate the possible therapeutic role of omeprazole, a powerful proton pump inhibitor, in unselected patients presenting with upper gastrointestinal bleeding. DESIGN--Double blind placebo controlled parallel group study. Active treatment was omeprazole 80 mg intravenously immediately, then three doses of 40 mg intravenously at eight hourly intervals, then 40 mg orally at 12 hourly intervals. Treatment was started within 12 hours of admission and given for four days or until surgery, discharge, or death. SETTING--The medical wards of University and City Hospitals, Nottingham. SUBJECTS--1147 consecutive patients aged 18 years or more admitted over 40 months with acute upper gastrointestinal bleeding. MAIN OUTCOME MEASURES--Mortality from all causes; rate of rebleeding, transfusion requirements, and operation rate; effect of treatment on endoscopic appearances at initial endoscopy. RESULTS--Of 1147 patients included in the intention to treat analysis, 569 received placebo and 578 omeprazole. No significant differences were found between the placebo and omeprazole groups for rates of transfusion (302 (53%) placebo v 298 (52%) omeprazole), rebleeding (100 (18%) v 85 (15%)), operation (63 (11%) v 62 (11%)), and death (30 (5.3%) v 40 (6.9%)). However, there was an unexpected but significant reduction in endoscopic signs of upper gastrointestinal bleeding in patients treated with omeprazole compared with those treated with placebo (236 (45%) placebo v 176 (33%) omeprazole; p less than 0.0001). CONCLUSIONS--Omeprazole failed to reduce mortality, rebleeding, or transfusion requirements, although the reduction in endoscopic signs of bleeding suggests that inhibition of acid may be capable of influencing intragastric bleeding. Our data do not justify the routine use of acid inhibiting drugs in the management of haematemesis and melaena.     

Effects of acupuncture on rates of pregnancy and live birth among women undergoing in vitro fertilisation: systematic review and meta-analysis

Objective To evaluate whether acupuncture improves rates of pregnancy and live birth when used as an adjuvant treatment to embryo transfer in women undergoing in vitro fertilisation.Design Systematic review and meta-analysis.Data sources Medline, Cochrane Central, Embase, Chinese Biomedical Database, hand searched abstracts, and reference lists.Review methods Eligible studies were randomised controlled trials that compared needle acupuncture administered within one day of embryo transfer with sham acupuncture or no adjuvant treatment, with reported outcomes of at least one of clinical pregnancy, ongoing pregnancy, or live birth. Two reviewers independently agreed on eligibility; assessed methodological quality; and extracted outcome data. For all trials, investigators contributed additional data not included in the original publication (such as live births). Meta-analyses included all randomised patients.Data synthesis Seven trials with 1366 women undergoing in vitro fertilisation were included in the meta-analyses. There was little clinical heterogeneity. Trials with sham acupuncture and no adjuvant treatment as controls were pooled for the primary analysis. Complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (odds ratio 1.65, 95% confidence interval 1.27 to 2.14; number needed to treat (NNT) 10 (7 to 17); seven trials), ongoing pregnancy (1.87, 1.40 to 2.49; NNT 9 (6 to 15); five trials), and live birth (1.91, 1.39 to 2.64; NNT 9 (6 to 17); four trials). Because we were unable to obtain outcome data on live births for three of the included trials, the pooled odds ratio for clinical pregnancy more accurately represents the true combined effect from these trials rather than the odds ratio for live birth. The results were robust to sensitivity analyses on study validity variables. A prespecified subgroup analysis restricted to the three trials with the higher rates of clinical pregnancy in the control group, however, suggested a smaller non-significant benefit of acupuncture (odds ratio 1.24, 0.86 to 1.77).Conclusions Current preliminary evidence suggests that acupuncture given with embryo transfer improves rates of pregnancy and live birth among women undergoing in vitro fertilisation.     

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation

ObjectiveTo examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indoprofen) in patients with non-rheumatic atrial fibrillation.MethodsMeta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects.ResultsNo trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others.ConclusionsThe heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.     

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers.

OBJECTIVE: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. DESIGN: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. SETTING: One university hospital. SUBJECTS: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. MAIN OUTCOME MEASURES: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. RESULTS: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). CONCLUSION: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage.     

Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis

There is a lack of consensus regarding which type of antiplatelet agent should be used in patients with peripheral arterial disease (PAD) and little is known on the advantages and disadvantages of dual antiplatelet therapy. We conducted a systematic review and network meta-analysis of available randomized controlled trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine, Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or in combination with aspirin) in PAD patients (PROSPERO public database; CRD42014010299).We collated evidence from previous relevant meta-analyses and searched online databases. Primary efficacy endpoints were: (1) the composite rate of major adverse cardiovascular events (MACE; including vascular deaths, non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major leg amputations. The primary safety endpoint was the rate of severe bleeding events. Bayesian models were employed for multiple treatment comparisons and risk-stratified hierarchies of comparative efficacy were produced to aid medical decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are reported in case of significant results. We analyzed 49 RCTs comprising 34,518 patients with 88,358 person-years of follow-up with placebo as reference treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in reducing MACE. A significant MACE reduction was noted with Ticagrelor plus aspirin (RR: 0.67; 95%CrI: 0.46–0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI: 0.58–0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58–0.96, NNT = 87), and Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61–0.99, NNT = 98). Dual antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46–0.99 compared to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with Ticlopidine (RR: 5.03; 95%CrI: 1.23–39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI: 1.22–2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05–2.10, NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm profile (79% cumulative rank probability best and 77% cumulative rank probability safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce the rate of major leg amputations following revascularization, but carries a slightly higher risk of severe bleeding.     

Optimal timing of operation for bleeding peptic ulcer: prospective randomised trial.

From October 1980 to September 1983 all patients with upper gastrointestinal bleeding were admitted to a centralised unit and investigated by early endoscopy. A total of 142 patients with a proved duodenal or gastric ulcer were randomised after stratification for age and site of ulcer to early (aggressive) surgical management or a delayed (conservative) policy. Significantly more operations (n = 42; 60%) were performed in the early than in the delayed (n = 9; 20%) groups (p less than 0.01). There were no deaths among the 42 patients under 60. The overall mortality in the 100 patients aged over 60 was 10% and when analysed on an "intention to treat" basis there was no difference between early and delayed surgery. When, however, an unrelated death from a bleeding colonic polyp was excluded and the data analysed on "treatment received" the mortality was only 2% in the early group compared with 13% in the delayed group (p less than 0.05). When analysis was confined to gastric ulcer the difference between early (0%) and delayed (24%) treatment was even greater. The results of this trial indicate that for patients over 60 an aggressive surgical policy is associated with a significant reduction in mortality.     

Antithrombin III in critically ill patients: systematic review with meta-analysis and trial sequential analysis

Objective To evaluate the benefits and harms of antithrombin III in critically ill patients.Design Systematic review and meta-analysis of randomised trials.Data sources CENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (to November 2006); hand search of reference lists, contact with authors and experts, and search of registers of ongoing trials.Review methods Two reviewers independently selected parallel group randomised clinical trials comparing antithrombin with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. Disagreements were resolved by discussion. Trials in any type of critically ill patients in intensive care were eligible. All trials, irrespective of blinding or language status, that compared any antithrombin III regimen with no intervention or placebo were included. Trials were considered to be at low risk of bias if they had adequate randomisation procedure, blinding, and used intention to treat analysis. Risk ratios with 95% confidence intervals were estimated with fixed and random effects models according to heterogeneity. Main outcome measures Mortality, length of stay in intensive care or hospital, quality of life, severity of sepsis, respiratory failure, duration of mechanical ventilation, incidence of surgical intervention, intervention effect among various populations, and adverse events (such as bleeding).Results 20 trials randomly assigning 3458 patients met inclusion criteria. Eight trials had low risk of bias. Compared with placebo or no intervention, antithrombin III did not reduce overall mortality (relative risk 0.96, 95% confidence interval 0.89 to 1.03). No subgroup analyses on risk of bias, populations of patients, or with and without adjuvant heparin yielded significant results. Antithrombin III increased the risk of bleeding events (1.52, 1.30 to 1.78). Heterogeneity was observed in only a few analyses.Conclusion Antithrombin III cannot be recommended for critically ill patients based on the available evidence.     

The Influential Roles of Antibiotics Prophylaxis in Cirrhotic Patients with Peptic Ulcer Bleeding after Initial Endoscopic Treatments

The influential roles of antibiotic prophylaxis on cirrhotic patients with peptic ulcer bleeding are still not well documented. The purpose of this study is to clarify these influential roles and to identify the risk factors associated with rebleeding, bacterial infection and in-hospital mortality. A cross-sectional, chart review study was conducted on 210 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients were divided into group A (with prophylactic intravenous ceftriaxone, n = 74) and group B (without antibiotics, n = 136). The outcomes were length of hospital days, prevention of infection, rebleeding rate and in-hospital mortality. Our results showed that more patients suffered from rebleeding and infection in group B than group A (31.6% vs. 5.4%; p<0.001 and 25% vs. 10.8%; p = 0.014 respectively). The risk factors for rebleeding were active alcoholism, unit of blood transfusion, Rockall score, model for end-stage liver disease score and antibiotic prophylaxis. The risk factors for infection were active alcoholism, Child-Pugh C, Rockall score and antibiotic prophylaxis. Rockall score was the predictive factor for in-hospital mortality. In conclusions, antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and rebleeding rate but not in-hospital mortality. Rockall score was the predictive factor of in-hospital mortality.     

Effect of training and lifting equipment for preventing back pain in lifting and handling: systematic review

Objectives To determine whether advice and training on working techniques and lifting equipment prevent back pain in jobs that involve heavy lifting.Data sources Medline, Embase, CENTRAL, Cochrane Back Group’s specialised register, CINAHL, Nioshtic, CISdoc, Science Citation Index, and PsychLIT were searched up to September-November 2005.Review methods The primary search focused on randomised controlled trials and the secondary search on cohort studies with a concurrent control group. Interventions aimed to modify techniques for lifting and handling heavy objects or patients and including measurements for back pain, consequent disability, or sick leave as the main outcome were considered for the review. Two authors independently assessed eligibility of the studies and methodological quality of those included. For data synthesis, we summarised the results of studies comparing similar interventions. We used odds ratios and effect sizes to combine the results in a meta-analysis. Finally, we compared the conclusions of the primary and secondary analyses.Results Six randomised trials and five cohort studies met the inclusion criteria. Two randomised trials and all cohort studies were labelled as high quality. Eight studies looked at lifting and moving patients, and three studies were conducted among baggage handlers or postal workers. Those in control groups received no intervention or minimal training, physical exercise, or use of back belts. None of the comparisons in randomised trials (17 720 participants) yielded significant differences. In the secondary analysis, none of the cohort studies (772 participants) had significant results, which supports the results of the randomised trials.Conclusions There is no evidence to support use of advice or training in working techniques with or without lifting equipment for preventing back pain or consequent disability. The findings challenge current widespread practice of advising workers on correct lifting technique.     

Aprotinin May Increase Mortality in Low and Intermediate Risk but Not in High Risk Cardiac Surgical Patients Compared to Tranexamic Acid and ε-Aminocaproic Acid – A Meta-Analysis of Randomised and Observational Trials of over 30.000 Patients

Background

To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and ε-aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery.

Methods and Findings

We performed a meta-analysis of randomised controlled trials and observational with the following data sources: Medline, Cochrane Library, and reference lists of identified articles. The primary outcome measure was early (in-hospital/30-day) mortality. The secondary outcome measures were any transfusion of packed red blood cells within 24 hours after surgery, any re-operation for bleeding or massive bleeding, and acute renal dysfunction or failure within the selected cited publications, respectively.Out of 328 search results, 31 studies (15 trials and 16 observational studies) included 33,501 patients. Early mortality was significantly increased after aprotinin vs. lysine analogues with a pooled risk ratio (95% CI) of 1.58 (1.13–2.21), p<0.001 in the low (n = 14,297) and in the intermediate risk subgroup (1.42 (1.09–1.84), p<0.001; n = 14,427), respectively. Contrarily, in the subgroup of high risk patients (n = 4,777), the risk for mortality did not differ significantly between aprotinin and lysine analogues (1.03 (0.67–1.58), p = 0.90).

Conclusion

Aprotinin may be associated with an increased risk of mortality in low and intermediate risk cardiac surgery, but presumably may has no effect on early mortality in a subgroup of high risk cardiac surgery compared to lysine analogues. Thus, decisions to re-license aprotinin in lower risk patients should critically be debated. In contrast, aprotinin might probably be beneficial in high risk cardiac surgery as it reduces risk of transfusion and bleeding complications.     

Current Management Strategies in Acid-Related Disorders

Acid-related disorders include not only reflux esophagitis and peptic ulcer, but also a subset of patients with endoscopy-negative dyspepsia. The management strategy differs between these diseases and therefore a precise diagnosis is important. The unaided clinical diagnosis is of limited value in patients with pain or discomfort in the upper abdomen, and endoscopy is therefore an important and cost-effective diagnostic tool.Duodenal ulcer is caused by an interplay between gastric acid and Helicobacter pylori. The treatment is aimed at rapid symptom relief and healing and at the same time eradication of H. pylori. At present the best choice is the combination of a proton pump inhibitor and two effective antimicrobial drugs, e.g., clarithromycin and metronidazole. The proton pump inhibitor has dual effect in this combination it provides optimal symptom relief and healing, and it increases the anti-H. pylori-effect of the antimicrobial drugs. The risk of reinfection varies geographically; in Europe it is around 1 percent per year, and cure of the infection provides long-term, maybe life-long, cure of the ulcer disease. Some gastric ulcers are not H. pylori-related and the treatment strategy therefore includes a diagnostic test for this infection. If positive, treatment is similar to that in duodenal ulcer, while H. pylori-negative gastric ulcer patients are treated with antisecretory drugs alone.Reflux esophagitis correlates with the degree of acid exposure to the esophagus, and intensive acid inhibition is the most effective non-surgical therapy. In most cases the disease is chronic and needs continuous long-term therapy to prevent relapse. A staged reduction in dosage of the acid inhibitory drug may be attempted when the esophagitis is healed and the patient has become symptom free, but full dose therapy is often needed.Patients with endoscopy-negative dyspepsia are a heterogenous group and a more precise identification of the cause of the symptoms is a prerequisite for rational treatment. Empiric treatment can be tried in patients without alarm symptoms like bleeding or a palpable abdominal mass, and often an acid inhibitory drug is used. A more precise identification of those patients who have acid-related symptoms is possible using placebo controlled single-subject trials with an effective acid inhibitory drug, but in daily routine these drugs are simply given for a short period of time, and in case symptomatic relief is observed, the symptoms may be regarded as being acid-related and treated accordingly.     

Duodenal ulcer and gastroesophageal reflux disease today: long-term therapy--a sideways glance.

Acid-peptic disease is widely considered conquered or controlled, future advances being refinements of existing treatments rather than radical new developments. Yet controversies remain and developments have yet to be made. DUODENAL ULCER: Daily maintenance treatment with the anti-secretory drugs, histamine H2 receptor antagonists and proton pump blockers, controls duodenal ulcer effectively, markedly reducing relapse rate at one year after treatment from about 75 percent to 15 to 20 percent (and to about 10 percent on proton pump blockers). In contrast, Helicobacter pylori eradication with a one to two week course of treatment yields prolonged remission or cure. The consequent reduction in drug costs in individual patients, however, has been exceeded by increasing community use on the more expensive proton pump blockers for the treatment of gastroesophageal reflux disease. The marked decline in elective surgery since the introduction of histamine H2 receptor antagonists is commonly attributed to the power of these drugs. The fall, however, had started much earlier, indicating that the decline is due to changing natural history. In contrast, complication rates remain unaltered. An increasing proportion of newly diagnosed duodenal ulcer patients are elderly, and more of them now present for the first time with complications (in this center, about 40 percent), which consequently cannot be forestalled. Thus, duodenal ulcer disease is likely to remain a problem and in many will be a serious illness. GASTROESOPHAGEAL REFLUX DISEASE: The proton pump blockers have revolutionized the treatment of gastroesophageal reflux disease. In clinical trials they have proven markedly superior to the histamine H2 receptor antagonists in healing (at eight weeks, 80 to 90 percent vs. 50 to 60 percent), symptom relief, prevention of relapse on maintenance therapy and cost-effectiveness. However, several issues remain. The prevalence of gastroesophageal reflux disease seems to be rising and is now probably the commonest acid-peptic disease encountered in the West. Most clinical trials comparing proton pump blockers vs. histamine H2 receptor antagonists have been done in patients with erosive esophagitis, whereas the majority (50 to 60 percent) of patients with gastroesophageal reflux disease have milder, generally non-erosive, disease. The therapeutic gain of proton pump blockers diminishes in mild disease so may not be worth the higher drug costs. This is an important area for investigation. The majority of patients with erosive esophagitis relapse when treatment is stopped (about 75 percent at one year). Relapse is markedly reduced (to 20 to 25 percent) by daily maintenance treatment with proton pump blockers. Mild disease relapses less often, so longterm therapy by intermittent treatment may prove acceptable and more cost-effective than maintenance treatment. This strategy remains unexplored in trials. The ideal profile of an anti-secretory drug for intermittent treatment would combine rapid onset of action (similar to histamine H2 receptor antagonists) with powerful effect (as with proton pump blockers). The new class of drug, the reversible proton pump blocker (e.g., BY841) approaches this requirement.     

Effects of fibrinolytic inhibitors on mortality from upper gastrointestinal haemorrhage.

OBJECTIVE--To see whether fibrinolytic inhibitors are of value when given to patients with upper gastrointestinal haemorrhage. DESIGN--Meta-analysis of six randomised double blind placebo controlled trials. Two methods used for obtaining an overall estimate of effect, including a random effects model incorporating any heterogeneity of outcome in the estimate of the overall treatment effect. SETTING--Inpatient care in hospitals in the United Kingdom, Sweden, and Australia. PATIENTS--1267 Patients admitted to hospital with primary diagnosis of acute upper gastrointestinal haemorrhage. Five of the six trials included a high proportion of elderly patients. Most patients were bleeding from peptic ulcers in the stomach and duodenum (43-88%) or gastric erosions (4-23%). A variable proportion had a degree of clinical shock at entry. INTERVENTIONS--Tranexamic acid 3-6 g/day given intravenously for two or three days followed by 3-6 g/day by mouth for a further three to five days (four trials) or 4.5-12 g/day by mouth for two to seven days (two trials). END POINTS--Frequency of recurrent haemorrhage, need for surgery, and death. MAIN RESULTS--Treatment with tranexamic acid was associated with a 20-30% reduction in the rate of rebleeding, a 30-40% reduction (95% confidence interval 10% to 60%) in mortality. CONCLUSIONS--Treatment with tranexamic acid may be of value to patients considered to be at risk of dying after an upper gastrointestinal haemorrhage.     

Efficacy,tolerability, and upper gastrointestinal safety of celecoxib for treatment of osteoarthritis and rheumatoid arthritis: systematic review of randomised controlled trials

ObjectiveTo determine the efficacy, gastrointestinal safety, and tolerability of celecoxib (a cyclo-oxygenase 2 (COX 2) inhibitor) used in the treatment of osteoarthritis and rheumatoid arthritis.DesignSystematic review of randomised trials that compared at least 12 weeks'' celecoxib treatment with another non-steroidal anti-inflammatory drug (NSAID) or placebo and reported efficacy, tolerability, or safety. Trials identified from manufacturer and by searching electronic databases and evaluated according to predefined inclusion and quality criteria. Data combined through meta-analysis.Participants15 187 patients with osteoarthritis or rheumatoid arthritis.ResultsNine randomised controlled trials were included. Celecoxib and NSAIDS were equally effective for all efficacy outcomes. Compared with those taking other NSAIDs, in patients taking celecoxib the rate of withdrawals due to adverse gastrointestinal events was 46% lower (95% confidence interval 29% to 58%; NNT 35 at three months), the incidence of ulcers detectable by endoscopy was 71% lower (59% to 79%; NNT 6 at three months), and the incidence of symptoms of ulcers, perforations, bleeds, and obstructions was 39% lower (4% to 61%; NNT 208 at six months). Subgroup analysis of patients taking aspirin showed that the incidence of ulcers detected by endoscopy was reduced by 51% (14% to 72%) in those given celecoxib compared with other NSAIDs. The reduction was greater (73%, 52% to 84%) in those not taking aspirin.ConclusionCelecoxib is as effective as other NSAIDs for relief of symptoms of osteoarthritis and rheumatoid arthritis and has significantly improved gastrointestinal safety and tolerability.

What is already known on this topic

Long term NSAID use is associated with the development of peptic and duodenal ulcersCOX 2 specific inhibitors are claimed to cause fewer gastrointestinal complicationsThe National Institute for Clinical Excellence has recently recommended that COX 2 specific inhibitors are used in patients with arthritis who are at risk of gastrointestinal complications but not in those taking prophylactic aspirin

What this study adds

Systematic review of randomised trials shows that celecoxib is as effective as other NSAIDs for osteoarthritis and rheumatoid arthritisCelecoxib has significantly improved gastrointestinal safety and tolerability compared with standard NSAIDsAn improvement in gastrointestinal safety was still evident in patients who were also taking aspirin     

Vitamin A supplementation in infectious diseases: a meta-analysis.

OBJECTIVE--To study the effect of vitamin A supplementation on morbidity and mortality from infectious disease. DESIGN--A meta-analysis aimed at identifying and combining mortality and morbidity data from all randomised controlled trials of vitamin A. RESULTS--Of 20 controlled trials identified, 12 trials were randomised trials and provided "intention to treat" data: six community trials in developing countries, three in children admitted to hospital with measles, and three in very low birth weight infants. Combined results for community studies suggest a reduction of 30% (95% confidence interval 21% to 38%; two tailed p < 0.0000001) in all cause mortality. Analysis of cause specific mortality showed a reduction in deaths from diarrhoeal disease (in community studies) by 39% (24% to 50%; two tailed p < 0.00001); from respiratory disease (in measles studies) by 70% (15% to 90%; two tailed p = 0.02); and from other causes of death (in community studies) by 34% (15% to 48%; two tailed p = 0.001). Reductions in morbidity were consistent with the findings for mortality, but fewer data were available. CONCLUSIONS--Adequate supply of vitamin A, either through supplementation or adequate diet, has a major role in preventing morbidity and mortality in children in developing countries. In developed countries vitamin A may also have a role in those with life threatening infections such as measles and those who may have a relative deficiency, such as premature infants.     

Early enteral feeding versus "nil by mouth" after gastrointestinal surgery: systematic review and meta-analysis of controlled trials

ObjectiveTo determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes.DesignSystematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials.ResultsEleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046).ConclusionsThere seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.

What is already known on this topic

Enteral feeding within 24 hours after gastrointestinal surgery is toleratedTheoretically, early enteral feeding improves tissue healing and reduces septic complications after gastrointestinal surgery

What this study adds

There is no benefit in keeping patients “nil by mouth” after gastrointestinal surgerySeptic complications and length of hospital stay were reduced in those patients who received early enteral feedingIn patients who received early enteral feeding there were no significant reductions in incidence of anastomotic dehiscence, wound infection, pneumonia, intra-abdominal abscess, and mortality     

Confidence in results of beta-blocker postinfarction trials.

Seventeen published trials of beta-blockers in myocardial infarction were scrutinised for the 95% confidence limits for the reported treatment effects. All the trials were prospective, randomised, and (except when treatment was given intravenously) placebo controlled. For analysis of pooled results the trials were divided arbitrarily according to whether treatment had been given "early" or "late" after the onset of pain. All trials were consistent with a treatment effect of just over 20%, but benefit was more apparent in trials using late intervention with beta-blockers. The pooled results of trials using early intervention showed a positive effect of 8%, whereas those using late intervention showed a 26% reduction in mortality and confidence limits of 17-35%. The results confirm that late intervention with beta-blockers after myocardial infarction reduces mortality but show that the effect of early intervention remains to be determined.     

Cholesterol lowering and mortality: the importance of considering initial level of risk.

OBJECTIVE--To investigate the level of risk of death from coronary heart disease above which cholesterol lowering treatment produces net benefits. DESIGN--Meta-analysis of results of randomised controlled trials of cholesterol lowering treatments. METHODS--Published and unpublished data from all identified randomised controlled trials of cholesterol lowering treatments with six months or more follow up and with at least one death were included in the meta-analysis. The analyses were stratified by the rate of death from coronary heart disease in the control arms of the trials. MAIN OUTCOME MEASURES--Death from all causes, from coronary heart disease, and from causes other than coronary heart disease. RESULTS--In the pooled analysis, net benefit in terms of total mortality from cholesterol lowering was seen only for trials including patients at very high initial risk of coronary heart disease (odds ratio 0.74; 95% confidence interval 0.60 to 0.92). In a medium risk group no net effect was seen, and in the low risk group there were adverse treatment effects (1.22; 1.06 to 1.42). In a weighted regression analysis a significant (p < 0.001) trend of increasing benefit with increasing initial risk of coronary heart disease was shown. Raised mortality from causes other than coronary heart disease was seen in trials of drug treatment (1.21; 1.05 to 1.39) but not in the trials of non-drug treatments (1.02; 0.88 to 1.19). Cumulative meta-analysis showed that these results seem to have been stable as new trials appeared. CONCLUSION--Currently evaluated cholesterol lowering drugs seem to produce mortality benefits in only a small proportion of patients at very high risk of death from coronary heart disease. Population cholesterol screening could waste resources and even result in net harm in substantial groups of patients. Overall risk of coronary heart disease should be the main focus of clinical guidelines, and a cautious approach to the use of cholesterol lowering drugs should be advocated. Future trials should aim to clarify the level of risk above which treatment is of net benefit.     

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study

BackgroundColorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery.ConclusionThis study used robust consensus methodology to develop a core outcome set for use in colorectal cancer surgical trials. It is now necessary to validate the use of this set in research practice.     

Stereotactic Aspiration versus Craniotomy for Primary Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials

Background

A wealth of evidence based on the randomized controlled trials (RCTs) has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH) compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH.

Methods

According to the study strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries, relevant journals and the lists of references were also searched. After literature searching, two investigators independently performed literature screening, assessment of quality of the included trials and data extraction. The outcome measures included death or dependence, total risk of complication, and the risk of rebleeding, gastrointestinal hemorrhage and systematic infection.

Results

Four RCTs with 2996 participants were included. The quality of the included trials was acceptable. Stereotactic aspiration significantly decreased the odds of death or dependence at the final follow-up (odds ratio (OR): 0.80, 95% confidence interval (CI): 0.69–0.93; P = 0.004) and the risk of intracerebral rebleeding (OR: 0.44, 95% CI: 0.26–0.74; P = 0.002) compared to craniotomy with no significant heterogeneity among the study results.

Conclusions

The present meta-analysis provides evidence that the stereotactic aspiration may be associated with a reduction in the odds of being dead or dependent in primary ICH, which should be interpreted with caution. Further trials are needed to identify those patients most likely to benefit from the stereotactic aspiration.