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Background

Colonoscopes are designed with balance between flexibility, required to negotiate angulations, and stiffness, required to counteract the propensity for looping in unfixed sections of the colon, which retards advancement of the instrument. Colonoscopy can be challenging with old instruments that have lost native stiffness and become less responsive to torquing.

A new intraluminal stiffening device has become available in two grades of stiffness. However, there is no published evidence of its effectiveness. This randomized, controlled trial was designed to determine the effectiveness of the stiffening wires in improving cecal intubation rate and time following routine application. A secondary analysis determines effectiveness of application only after intractable failure with the unaided colonoscope.

Methods

The colonoscope tested was an Olympus CF-100TL, approximately fifteen years old. Patients were randomly assigned to the unaided colonoscope or the standard or firm wire introduced routinely on entry into transverse colon. Each phase of colonoscopy was timed. Failure to advance the colonoscope for 5 minutes (despite usual manipulations to minimize looping) required switching to another intervention according to a prescribed methodology and the originally assigned intervention was recorded as failed.

Results

The study was terminated after accrual of 112 participants (target sample size 480) because the colonoscope required repairs (no damage attributable to stiffening wires) which would have been uneconomical. There were no statistically significant differences between per-protocol cecal intubation rates (81.1, 71.1 and 70.3 percent respectively), a finding which persisted after multiple imputation for a virtual sample size of 480. Similarly, there were no statistically significant differences between per-protocol cecal intubation times (15, 16.2 and 13.9 minutes). However, a statistically significant improvement in cecal intubation rate (from 81.1% to 97.3%, P = 0.0313) was achieved when the wires were applied after intractable failure of the unaided colonoscope in the first intervention group.

Conclusions

Routine application of either stiffening wire does not improve caecal intubation rate nor time compared to the unaided colonoscope. However, application of the stiffening wires after intractable failure of the unaided colonoscope enabled a statistically significant improvement in cecal intubation rate.

Trial Registration

clinicaltrials.gov Identifier: NCT01115010

Background

Safe and effective colonoscopy is aided by the use of endoscopic techniques and maneuvers (ETM) during the examination including patient repositioning, stiffening of the endoscope and abdominal pressure.

Aim

To better understand the use and value of ETM during colonoscopy by using a device that allows real-time imaging of the colonoscope insertion shaft.

Methods

The use of ETM during colonoscopy and their success was recorded. Experienced colonoscopists and endoscopy assistants used a commercially available electromagnetic (EM) transmitter and a special adult variable stiffness instrument with 12 embedded sensors to examine 46 patients. In 5 of these a special EM probe passed through the instrument channel of a standard pediatric variable stiffness colonoscope was used instead of the EM colonoscope.

Results

Thirty-nine men and 7 women with a mean age of 64 years (range 33–90) were studied. The cecum was intubated in 93.5% (43/46). The mean time to reach the cecum was 10.6 minutes (range 3–25). ETM were used a total of 174 times in 41 of the patients to assist with cecal intubation. When ETM were required to reach the cecum, and the cecum was intubated, an average of 3.82 ETM/patient was used. While ETM were used most often when the tip of the colonoscope was in the left side of the colon (rectum 5.0%, sigmoid colon 20.7%, descending colon 5.0%, and splenic flexure 11.6%), when the instrument was in the transverse colon (14.8%), hepatic flexure (20.7%) and ascending colon (19.8%) the use of ETM was also required. When the colonoscope tip was in the transverse colon, hepatic flexure and ascending colon, ETM success rates were less (61.1%, 52.0%, and 41.7% respectively) compared to the left colon success rates (rectum 83.3%, sigmoid colon 84.0%, descending colon 100%, and splenic flexure 85.7%).

Conclusion

The EM colonoscope allows imaging of the insertion shaft without fluoroscopy and is a useful device for evaluating the efficacy of ETM. ETM are important tools of the colonoscopist and are used most often in the left colon where they are most effective.

AIM

To evaluate the efficacy and safety of trabeculectomy, phacotrabeculectomy plus intraocular lens implantation(phacotrab+IOL group) and phacoemulsification with IOL(phaco+IOL) in primary angle-closure glaucoma(PACG).

METHODS

It was a systematic review and meta-analysis, randomized controlled trials(RCT) and clinical controlled trials(CCT) were collected through electronic searches of the Cochrane Library, PubMed, EMbase, Wanfang Database online, Chinese journal Full-text Database, Chinese Scientific Journals Full-text Database (from the date of building the database to October 2010) We also checked the bibliographies of retrieved articles. All the related data that matched our standards were abstracted. The quality of included trials was evaluated according to the Dutch Cochrane Centre. RevMan 5.0 software was used for Meta-analysis.

RESULTS

A total of 5 RCT and 11 CCT involving 1495 eyes were included. The results of meta-analysis showed that phacotrab+IOL group was superior than trabeculectomy(trab group) (MD -3.93,95%CI [-7.31, -0.54]) which was also superior than phaco+IOL group(MD 0.52,95%CI [0.10, 0.95]) in decreasing Intraocular Pressure(IOP). Phacotrab group(MD -1.45,95%CI [-1.68, -1.22])and phaco group (MD-1.12,95%CI [-1.87, -0.37])are both deeper than trab group in the anterior chamber depth. In increasing the coefficient of outflow facility of aqueous humor(C values) there was no statistical difference in the three groups. And there was no statistical difference between phacotrab groups and phaco groups in visual acuity but phacotrab group was superior than phaco group (MD 1.07, 95%CI [0.73, 1.40])in the use of IOP-lowering drugs. There was no statistical difference among three groups.

CONCLUSION

Current evidence suggests that phacotrab+ IOL group was superior than trab group which was also superior than phaco+IOL group in decreasing IOP. Phacotrab group and phaco group are both deeper than trab group in the anterior chamber depth. Phacotrab group was superior than phaco group in the use of IOP-lowering drugs.

AIM: To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding.

METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model.

RESULTS: Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929).

CONCLUSION: Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

There is indirect evidence to suggest that 80% of colorectal cancers (CRC) develop from adenomatous polyps and that, on average, it takes 10 years for a small polyp to transform into invasive CRC. In multiple cohort studies, colonoscopic polypectomy has been shown to significantly reduce the expected incidence of CRC by 76% to 90%. Colonoscopic polypectomy is performed frequently in primary outpatient clinics and secondary and tertiary medical centers in Korea. However, there are no evidence-based, procedural guidelines for the appropriate performance of this procedure, including the technical aspects. For the guideline presented here, PubMed, Medline, and Cochrane Library literature searches were performed. When little or no data from well-designed prospective trials were available, an emphasis was placed on the results from large series and reports from recognized experts. Thus, these guidelines for colonoscopic polypectomy are based on a critical review of the available data as well as expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data become available. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions for any particular case involve a complex analysis of the patient's condition and the available courses of action.

Background

Idiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.

Objectives

To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.

Methods

PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager.

Main Results

17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15).

Conclusions

This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

Background

A water method developed to attenuate discomfort during colonoscopy enhanced cecal intubation in unsedated patients. Serendipitously a numerically increased adenoma detection rate (ADR) was noted.

Objective

To explore databases of sedated patients examined by the air and water methods to identify hypothesis-generating findings. Design: Retrospective analysis. Setting: VA endoscopy center. Patients: creening colonoscopy. Interventions: From 1/2000–6/2006 the air method was used - judicious air insufflation to permit visualization of the lumen to aid colonoscope insertion and water spray for washing mucosal surfaces. From 6/2006–11/2009 the water method was adopted - warm water infusion in lieu of air insufflation and suction removal of residual air to aid colonoscope insertion. During colonoscope withdrawal adequate air was insufflated to distend the colonic lumen for inspection, biopsy and polypectomy in a similar fashion in both periods. Main outcome measurements: ADR.

Results

The air (n=683) vs. water (n=495) method comparisons revealed significant differences in overall ADR 26.8% (183 of 683) vs. 34.9% (173 of 495) and ADR of adenomas >9 mm, 7.2% vs. 13.7%, respectively (both P<0.05, Fisher's exact test). Limitations: Non-randomized data susceptible to bias by unmeasured parameters unrelated to the methods.

Conclusion

Confirmation of the serendipitous observation of an impact of the water method on ADR provides impetus to call for randomized controlled trials to test hypotheses related to the water method as an approach to improving adenoma detection. Because of recent concerns over missed lesions during colonoscopy, the provocative hypothesis-generating observations warrant presentation.

AIM: To conduct a meta-analysis to determine the safety and efficacy of laparoscopic liver resection (LLR) and open liver resection (OLR) for hepatocellular carcinoma (HCC).

METHODS: PubMed (Medline), EMBASE and Science Citation Index Expanded and Cochrane Central Register of Controlled Trials in the Cochrane Library were searched systematically to identify relevant comparative studies reporting outcomes for both LLR and OLR for HCC between January 1992 and February 2012. Two authors independently assessed the trials for inclusion and extracted the data. Meta-analysis was performed using Review Manager Version 5.0 software (The Cochrane Collaboration, Oxford, United Kingdom). Pooled odds ratios (OR) or weighted mean differences (WMD) with 95%CI were calculated using either fixed effects (Mantel-Haenszel method) or random effects models (DerSimonian and Laird method). Evaluated endpoints were operative outcomes (operation time, intraoperative blood loss, blood transfusion requirement), postoperative outcomes (liver failure, cirrhotic decompensation/ascites, bile leakage, postoperative bleeding, pulmonary complications, intraabdominal abscess, mortality, hospital stay and oncologic outcomes (positive resection margins and tumor recurrence).

RESULTS: Fifteen eligible non-randomized studies were identified, out of which, 9 high-quality studies involving 550 patients were included, with 234 patients in the LLR group and 316 patients in the OLR group. LLR was associated with significantly lower intraoperative blood loss, based on six studies with 333 patients [WMD: -129.48 mL; 95%CI: -224.76-(-34.21) mL; P = 0.008]. Seven studies involving 416 patients were included to assess blood transfusion requirement between the two groups. The LLR group had lower blood transfusion requirement (OR: 0.49; 95%CI: 0.26-0.91; P = 0.02). While analyzing hospital stay, six studies with 333 patients were included. Patients in the LLR group were found to have shorter hospital stay [WMD: -3.19 d; 95%CI: -4.09-(-2.28) d; P < 0.00001] than their OLR counterpart. Seven studies including 416 patients were pooled together to estimate the odds of developing postoperative ascites in the patient groups. The LLR group appeared to have a lower incidence of postoperative ascites (OR: 0.32; 95%CI: 0.16-0.61; P = 0.0006) as compared with OLR patients. Similarly, fewer patients had liver failure in the LLR group than in the OLR group (OR: 0.15; 95%CI: 0.02-0.95; P = 0.04). However, no significant differences were found between the two approaches with regards to operation time [WMD: 4.69 min; 95%CI: -22.62-32 min; P = 0.74], bile leakage (OR: 0.55; 95%CI: 0.10-3.12; P = 0.50), postoperative bleeding (OR: 0.54; 95%CI: 0.20-1.45; P = 0.22), pulmonary complications (OR: 0.43; 95%CI: 0.18-1.04; P = 0.06), intra-abdominal abscesses (OR: 0.21; 95%CI: 0.01-4.53; P = 0.32), mortality (OR: 0.46; 95%CI: 0.14-1.51; P = 0.20), presence of positive resection margins (OR: 0.59; 95%CI: 0.21-1.62; P = 0.31) and tumor recurrence (OR: 0.95; 95%CI: 0.62-1.46; P = 0.81).

CONCLUSION: LLR appears to be a safe and feasible option for resection of HCC in selected patients based on current evidence. However, further appropriately designed randomized controlled trials should be undertaken to ascertain these findings.

AIM: To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized, controlled trial data.

METHODS: The Third Eye® Retroscope® Randomized Clinical Evaluation (TERRACE) was a randomized, controlled, multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope’s forward view. We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device. Subjects were patients scheduled for colonoscopy for screening, surveillance or diagnostic workup, and each underwent same-day tandem examinations with standard colonoscopy (SC) and Third Eye colonoscopy (TEC), randomized to SC followed by TEC or vice versa.

RESULTS: Indication for colonoscopy was screening in 176/345 subjects (51.0%), surveillance after previous polypectomy in 87 (25.2%) and diagnostic workup in 82 (23.8%). In 4 subjects no indication was specified. Previously reported overall results had shown a net additional adenoma detection rate (ADR) with TEC of 23.2% compared to SC. Relative risk (RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92 (P = 0.029). Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening, 35.7% for surveillance, 55.4% for diagnostic and 40.7% for surveillance and diagnostic combined. The RR of missing adenomas with SC vs TEC was 1.11 (P = 0.815) for screening, 3.15 (P = 0.014) for surveillance, 8.64 (P = 0.039) for diagnostic and 3.34 (P = 0.003) for surveillance and diagnostic combined. Although a multivariate Poisson regression suggested gender as a possibly significant factor, subset analysis showed that the difference between genders was not statistically significant. Age, bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC. Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm, respectively (P = NS).

CONCLUSION: TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup, but not in screening patients (ClinicalTrials.gov Identifier: NCT01044732).

A systematic review and meta-analysis of randomized trials conducted by B. Joseph Elmunzer and colleagues reports that that flexible sigmoidoscopy-based screening reduces the incidence of colorectal cancer in average-risk patients, as compared to usual care or no screening.

Background

Randomized controlled trials (RCTs) have yielded varying estimates of the benefit of flexible sigmoidoscopy (FS) screening for colorectal cancer (CRC). Our objective was to more precisely estimate the effect of FS-based screening on the incidence and mortality of CRC by performing a meta-analysis of published RCTs.

Methods and Findings

Medline and Embase databases were searched for eligible articles published between 1966 and 28 May 2012. After screening 3,319 citations and 29 potentially relevant articles, two reviewers identified five RCTs evaluating the effect of FS screening on the incidence and mortality of CRC. The reviewers independently extracted relevant data; discrepancies were resolved by consensus. The quality of included studies was assessed using criteria set out by the Evidence-Based Gastroenterology Steering Group. Random effects meta-analysis was performed.

The five RCTs meeting eligibility criteria were determined to be of high methodologic quality and enrolled 416,159 total subjects. Four European studies compared FS to no screening and one study from the United States compared FS to usual care. By intention to treat analysis, FS-based screening was associated with an 18% relative risk reduction in the incidence of CRC (0.82, 95% CI 0.73–0.91, p<0.001, number needed to screen [NNS] to prevent one case of CRC = 361), a 33% reduction in the incidence of left-sided CRC (RR 0.67, 95% CI 0.59–0.76, p<0.001, NNS = 332), and a 28% reduction in the mortality of CRC (relative risk [RR] 0.72, 95% CI 0.65–0.80, p<0.001, NNS = 850). The efficacy estimate, the amount of benefit for those who actually adhered to the recommended treatment, suggested that FS screening reduced CRC incidence by 32% (p<0.001), and CRC-related mortality by 50% (p<0.001).

Limitations of this meta-analysis include heterogeneity in the design of the included trials, absence of studies from Africa, Asia, or South America, and lack of studies comparing FS with colonoscopy or stool-based testing.

Conclusions

This meta-analysis of randomized controlled trials demonstrates that FS-based screening significantly reduces the incidence and mortality of colorectal cancer in average-risk patients.

Please see later in the article for the Editors' Summary

Editor's Summary

Background

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Regular CRC screening has been shown to reduce the risk of dying from CRC by 16%, and CRC screening can identify early stage cancers in otherwise healthy people, which allows for early treatment and management of the disease. Screening for colorectal cancer is frequently performed using a flexible sigmoidoscopy (FS), which is a thin, flexible tube with a tiny camera and light on the end, allowing a doctor to look at the inside wall of the bowel and remove any small growths or polyps. Although screening may detect early cancers, the life-saving and health benefits of screening are uncertain because the polyp may not necessarily progress. This could lead to anxiety and unnecessary interventions and treatments amongst those screened. Randomized controlled trials (RCTs) are needed to determine all of the risks involved in cancer screenings, however the guidelines that recommend FS-based screening do not rely upon RCT data. Recently, the results of four large-scale RCTs evaluating FS screening for CRC have been published. The conflicting results with respect to the incidence and mortality of CRC in these studies have called into question the effectiveness of endoscopic screening.

Why Was This Study Done?

The results of RCTs measuring the risks and outcomes of CRC screening have shown varying estimates of the benefits of using FS screening. If better estimates of the risks and benefits of FS screening are developed, then the current CRC screening guidelines may be updated to reflect this new information. In this study, the authors show the results of a meta-analysis of published RCTs, which more precisely estimates the effects of FS-based screening on the incidence and mortality of colorectal cancer.

What Did the Researchers Do and Find?

The researchers used the Medline and Embase databases to find relevant studies from 1966 to May 28, 2012. After screening 3,319 citations and 29 potentially relevant articles, five RCTs of high methodologic quality and 416,159 total subjects evaluating the effect of FS screening on the incidence and mortality of CRC were identified. The data were extracted and random effects meta-analysis was performed. The meta-analysis revealed that FS-based screening was associated with an 18% relative risk reduction in the incidence of CRC (0.82, 95% CI 0.73–0.91, p<0.001, number needed to screen (NNS) to prevent one case of CRC = 361), a 33% reduction in the incidence of left-sided CRC (RR 0.67, 95% CI 0.59–0.76, p<0.001, NNS = 332), and a 28% reduction in the mortality of CRC (RR 0.72, 95% CI 0.65–0.80, p<0.001, NNS = 850). The amount of benefit for those who adhered to the recommended treatment suggested that FS screening reduced CRC incidence by 32% (p<0.001), and CRC-related mortality by 50% (p<0.001).

What Do These Findings Mean?

This meta-analysis of RCTs evaluating the effect of FS on CRC incidence and mortality demonstrates that a FS-based strategy for screening is very effective in reducing the incidence and mortality of CRC in patients. The current recommendations for endoscopic screening are based on observational studies, which may not accurately reflect the effect of FS-based screening on the incidence and mortality of CRC. Here, the authors performed a systematic review and meta-analysis of five recent RCTs to better estimate the true effect of FS-based screening on the incidence and mortality of CRC. Thus, the results of this meta-analysis may affect health policy, and directly impact patients and clinicians.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001352.

Cancer research UK provides comprehensive information about screening for colorectal cancers as does the UK National Screening Committee

PubMed Health has general information about colon cancer

The National Cancer Institute also has comprehensive resources on colorectal cancer and treatment

The Mayo Clinic provides an overview of all aspects of colon cancer

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases.

Design Meta-analysis of randomised controlled trials.

Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria.

Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry.

Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases.

BACKGROUND:

The role of adjuvant steroid therapy in the postoperative management of patients with biliary atresia (BA) is unclear.

OBJECTIVE:

To systematically review the literature and perform a meta-analysis to determine the efficacy of adjuvant steroid therapy post-Kasai portoenterostomy (KP) on BA outcome.

METHODS:

A systematic review and meta-analysis of randomized trials and/or observational studies that examined the role of steroids on BA outcomes published between January 1969 and June 2010 was conducted. Studies were identified using the Medline, PubMed, EMBASE and Cochrane databases.

RESULTS:

Sixteen observational studies and one randomized controlled trial (RCT) were found. Four of the 16 observational studies (160 participants) and the RCT (73 participants) met the entry criteria and were eligible to be included in the analysis. There was no statistically significant difference in the effect of steroids either on normalizing serum bilirubin levels at six months (pooled OR 1.48 [95% CI 0.67 to 3.28]) or in delaying the need for early liver transplantation (within the first year post-KP (pooled OR 0.59 [95% CI 0.21 to 1.72]).

CONCLUSION:

The present meta-analysis did not find a significant effect of steroid over standard therapy, either in normalizing serum bilirubin levels at six months or at delaying the need for early liver transplantation post-KP. RCT studies of sufficient size and comprehensive design using high-dose steroids are needed to determine the effectiveness of steroids on the short and intermediate post-KP outcomes for BA patients.

Design: Systematic review and meta-analysis of randomised controlled trials (RCTs).

Data sources: Medline, Embase, Scientific Citation Index, CINAHL, Cochrane Library, and conference abstracts in the past 2 years from the British Society for Rheumatology, the European League Against Rheumatism, the American College of Rheumatology, and the Osteoarthritis Research Society International.

Subjects: 10 RCTs including 1712 patients with either symptomatic OA of the knee (6 trials) or hip/knee (3 trials) or multiple joints (1 trial).

Main outcome measures: (a) effect size (ES) for pain, stiffness, and functional scores from baseline to end point; (b) rate ratio (RR) and number needed to treat for clinical response rate and patient preference for treatment.

Results: Paracetamol was effective in relieving pain due to OA (ES = 0.21, 95% confidence interval (CI) 0.02 to 0.41). Non-steroidal anti-inflammatory drugs (NSAIDs) were better than paracetamol for pain relief (ES = 0.20, 95% CI 0.10 to 0.30). Clinical response rate was higher with NSAIDs than with paracetamol (RR = 1.24, 95% CI 1.08 to 1.41), and the number of patients who preferred NSAIDs was more than twice the number of those preferring paracetamol (RR = 2.46, 95% CI 1.51 to 4.12). NSAIDs were associated with more frequent gastrointestinal discomfort than paracetamol (RR = 1.35, 95% CI 1.05 to 1.75).

Conclusion: Paracetamol is an effective agent for pain relief due to OA. Although safer, it is less effective than NSAIDs. For safety reasons paracetamol should be the first line treatment, with NSAIDs reserved for those who do not respond.

Background and Aim: Neutropenia is a serious adverse event for patients who are treated with cetuximab, an inhibitor of endothelial growth factor receptor. However, there is no consistent result of the relationship between cetuximab and neutropenia in randomized controlled trials (RCTs). We did a systematic review and meta-analysis of published RCTs to assess the overall risk of neutropenia associated with cetuximab.

Methods: PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and American Society of Clinical Oncology conferences were searched for relevant RCTs. Quantitative and qualitative analyses were carried out to evaluate the association between neutropenia and cetuximab. Both the fixed-effect model and random-effects model were used.

Results: A total of 7186 patients with a variety of advanced cancers from 14 trials were included in our analysis. The overall incidence of neutropenia in patients receiving cetuximab was 33% (95% CI 26, 43). Patients treated with cetuximab had a significantly increased risk of neutropenia compared with patients treated with control medication, with a relative risk (RR) of 1.12 (95% CI 1.05, 1.19; fixed-effect model). Risk varied with tumor type. Higher risks were observed in patients with colorectal carcinoma (RR 1.17; 95% CI 1.04, 1.32; fixed-effect model) and non-small cell lung cancer (RR 1.07; 95% CI 0.99, 1.16; fixed-effect model).

Conclusion: Cetuximab is associated with a significant risk of neutropenia in patients with advanced cancer receiving concurrent chemotherapy.

Aims

The prospect of weight gain discourages many cigarette smokers from quitting. Practice guidelines offer varied advice about managing weight gain after quitting smoking, but no systematic review and meta-analysis have been available. We reviewed evidence to determine whether behavioral weight control intervention compromises smoking cessation attempts, and if it offers an effective way to reduce post-cessation weight gain.

Methods

We identified randomized controlled trials that compared combined smoking treatment and behavioral weight control to smoking treatment alone for adult smokers. English-language studies were identified through searches of PubMed, Ovid MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials. Of 779 articles identified and 35 potentially relevant RCTs screened, 10 met criteria and were included in the meta-analysis.

Results

Patients who received both smoking treatment and weight treatment showed increased abstinence (OR=1.29, 95% CI=1.01,1.64) and reduced weight gain (g = -0.30, 95% CI=-0.63, -0.04) in the short term (<3 months) compared with patients who received smoking treatment alone. Differences in abstinence (OR=1.23, 95% CI=0.85, 1.79) and weight control (g= -0.17, 95% CI=-0.42, 0.07) were no longer significant in the long term (>6 months).

Conclusions

Findings provide no evidence that combining smoking treatment and behavioral weight control produces any harm and significant evidence of short-term benefit for both abstinence and weight control. However, the absence of long-term enhancement of either smoking cessation or weight control by the time-limited interventions studied to date provides insufficient basis to recommend societal expenditures on weight gain prevention treatment for patients who are quitting smoking.

Objective

To evaluate the relationship between different hCG priming-to-oocyte retrieval intervals and assisted reproductive technology (ART) outcome.

Methods

We systematically searched PubMed, EMBASE, the Cochrane Library, Science Citation Index, Chinese biomedicine (CBM) literature database, and Chinese Journal Full-text Database for randomized controlled trials (RCTs) published up to November 2010. Data was extracted from the studies by two independent reviewers. Statistical analysis was performed with Cochrane Collaboration’s Review Manager (RevMan) 5.0.2. From extracted data, Risk Ratio (RR) with 95% confidence interval (CI) was calculated.

Results

5 RCTs totaling 895 participants were included. Oocyte maturation rate was higher in the long interval group compared with short interval group (RR, 0.67; 95% CI, 0.62–0.73). There were no significant difference between the two groups with regard to fertilization rate (RR, 0.99; 95% CI, 0.94–1.04), implantation rate (RR, 0.91; 95% CI, 0.40–2.04), and pregnancy rate (RR, 0.79; 95% CI, 0.58–1.08).

Conclusion

The percentage of mature (MII) oocytes can be increased by prolonging the interval between hCG priming and oocyte retrieval. The prolonged interval could not increase the fertilization rate, implantation rate, and pregnancy rate. Although there was evidence to confirm the results, they still need to be confirmed by large-sample, multicenter, randomized controlled trials. The time interval dependent mechanisms responsible for ART performance need to be elucidated.

Objectives:

To assess the efficacy and safety of steroid injections for patients with tendonitis of the shoulder or elbow.

Methods:

A systematic review of the literature using PubMed, EMBASE, the Cochrane library and manual searches was performed until April 2008. All randomised controlled trials (RCTs) reporting the efficacy on pain or functional disability, and/or the safety of steroid injections, versus placebo, non-steroidal anti-inflammatory drugs (NSAIDs) or physiotherapy in patients with tendonitis were selected. Pooled effect size (ES) was calculated by meta-analysis using the Mantel–Haenszel method.

Results:

In all, 20 RCTs were analysed (744 patients treated by injections and 987 patients treated by controls; 618 shoulders and 1113 elbows). The pooled analysis indicated only short-term effectiveness of steroids versus the pooled controls for pain and function (eg, pain at week 1–3 ES = 1.18 (95% CI 0.27 to 2.09), pain at week 4–8 ES = 1.30 (95% CI 0.55 to 2.04), pain at week 12–24 ES = −0.38 (95% CI −0.85 to 0.08) and pain at week 48 ES = 0.07 (95% CI −0.60 to 0.75)). Sensitivity analyses indicated similar results whatever the localisation, type of steroid and type of comparator except for NSAIDs: steroid injections were not significantly better than NSAIDs in the short-term. Steroid injections appeared more effective than pooled other treatments in acute or subacute tendonitis. The main side effects were transient pain after injection (10.7% of corticosteroid injections) and skin modification (4.0%).

Conclusions:

Steroid injections are well tolerated and more effective for tendonitis in the short-term than pooled other treatments, though similar to NSAIDs. No long-term benefit was shown.

BACKGROUND

Point-of-care practice audits allow documentation of procedural outcomes to support quality improvement in endoscopic practice.

OBJECTIVE

To evaluate a colonoscopists’ practice audit tool that provides point-of-care data collection and peer-comparator feedback.

METHODS

A prospective, observational colonoscopy practice audit was conducted in academic and community endoscopy units for unselected patients undergoing colonoscopy. Anonymized colonoscopist, patient and practice data were collected using touchscreen smart-phones with automated data upload for data analysis and review by participants. The main outcome measures were the following colonoscopy quality indicators: colonoscope insertion and withdrawal times, bowel preparation quality, sedation, immediate complications and polypectomy, and biopsy rates.

RESULTS

Over a span of 16 months, 62 endoscopists reported on 1279 colonoscopy procedures. The mean cecal intubation rate was 94.9% (10th centile 84.2%). The mean withdrawal time was 8.8 min and, for nonpolypectomy colonoscopies, 41.9% of colonoscopists reported a mean withdrawal time of less than 6 min. Polypectomy was performed in 37% of colonoscopies. Independent predictors of polypectomy included the following: endoscopy unit type, patient age, interval since previous colonoscopy, bowel preparation quality, stable inflammatory bowel disease, previous colon polyps and withdrawal time. Withdrawal times of less than 6 min were associated with lower polyp removal rates (mean difference −11.3% [95% CI −2.8% to −19.9%]; P=0.01).

DISCUSSION

Cecal intubation rates exceeded 90% and polypectomy rates exceeded 30%, but withdrawal times were frequently shorter than recommended. There are marked practice variations consistent with previous observations.

CONCLUSION

Real-time, point-of-care practice audits with prompt, confidential access to outcome data provide a basis for targeted educational programs to improve quality in colonoscopy practice.

AIM: To compare the effects of telbivudine (LDT) and entecavir (ETV) in treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B by meta-analysis.

METHODS: We conducted a literature search using PubMed, MEDLINE, EMBASE, the China National Knowledge Infrastructure, the VIP database, the Wanfang database and the Cochrane Controlled Trial Register for all relevant articles published before April 1, 2012. Randomized controlled trials (RCTs) comparing LDT with ETV for treatment of HBeAg-positive chronic hepatitis B were included. The data was analyzed with Review Manager Software 5.0. We used relative risk (RR) as an effect measure, and reported its 95% CI. Meta-analysis was performed using either a fixed-effect or random-effect model, based on the absence or presence of significant heterogeneity. Two reviewers assessed the risk of bias and extracted data independently and in duplicate. The analysis was executed using the main outcome parameters including hepatitis B virus (HBV) DNA undetectability, alanine aminotransferase (ALT) normalization, HBeAg loss, HBeAg seroconversion, drug-resistance, and adverse reactions. Meta-analysis of the included trials and subgroup analyses were conducted to examine the association between pre-specified characteristics with the therapeutic effects of the two agents.

RESULTS: Thirteen eligible trials (3925 patients in total) were included and evaluated for methodological quality and heterogeneity. In various treatment durations of 4 wk, 8 wk, 12 wk, 24 wk, 36 wk, 48 wk, 52 wk, 60 wk and 72 wk, the rates of HBV DNA undetectability and ALT normalization in the two groups were similar, without statistical significance. At 4 wk and 8 wk of the treatment, no statistical differences were found in the rate of HBeAg loss between the two groups, while the rate in the LDT group was higher than in the ETV group at 12 wk, 24 wk, 48 wk and 52 wk, respectively (RR 2.28, 95% CI 1.16, 7.03, P = 0.02; RR 1.45, 95% CI 1.16, 1.82, P = 0.001; RR 1.45, 95% CI 1.11, 1.89, P = 0.006; and RR 1.86, 95% CI 1.04, 3.32, P = 0.04). At 4 wk, 8 wk, 60 wk and 72 wk of the treatment, there were no significant differences in the rate of HBeAg seroconversion between the two groups, while at 12 wk, 24 wk, 48 wk and 52 wk, the rate in the LDT group was higher than in the ETV group (RR 2.10, 95% CI 1.36, 3.24, P = 0.0008; RR 1.71, 95% CI 1.29, 2.28, P = 0.0002; RR 1.86, 95% CI 1.36, 2.54, P < 0.0001; and RR 1.87, 95% CI 1.21, 2.90, P = 0.005). The rate of drug-resistance was higher in the LDT group than in the ETV group (RR 3.76, 95% CI 1.28, 11.01, P = 0.02). In addition, no severe adverse drug reactions were observed in the two groups. And the rate of increased creatine kinase in the LDT group was higher than in the ETV group (RR 5.58, 95% CI 2.22, 13.98, P = 0.0002).

CONCLUSION: LDT and ETV have similar virological and biomedical responses, and both are safe and well tolerated. However, LDT has better serological response and higher drug-resistance.

Background

Relaxation training is a common treatment for anxiety problems. Lacking is a recent quantitative meta-analysis that enhances understanding of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment.

Methods

All studies (1997–2007), both RCT, observational and without control group, evaluating the efficacy of relaxation training (Jacobson's progressive relaxation, autogenic training, applied relaxation and meditation) for anxiety problems and disorders were identified by comprehensive electronic searches with Pubmed, Psychinfo and Cochrane Registers, by checking references of relevant studies and of other reviews. Our primary outcome was anxiety measured with psychometric questionnaires. Meta-analysis was undertaken synthesizing the data from all trials, distinguishing within and between effect sizes.

Results

27 studies qualified for the inclusion in the meta-analysis. As hypothesized, relaxation training showed a medium-large effect size in the treatment of anxiety. Cohen's d was .57 (95% CI: .52 to .68) in the within analysis and .51 (95% CI: .46 to .634) in the between group analysis. Efficacy was higher for meditation, among volunteers and for longer treatments. Implications and limitations are discussed.

Conclusion

The results show consistent and significant efficacy of relaxation training in reducing anxiety. This meta-analysis extends the existing literature through facilitation of a better understanding of the variability and clinical significance of anxiety improvement subsequent to relaxation training.

Objective. The purpose of this study was to determine the database indexing of randomized controlled trials (RCTs) for a meta-analysis addressing the effects of exercise on pain and physical function in adults with arthritis and other rheumatic diseases (AORD). Methods. The number, percentage, and 95% confidence intervals (CIs) for included articles at initial and follow-up periods were calculated from PubMed, EMBASE, CENTRAL, CINAHL, SPORTDiscus, and DAO databases. The number needed to review (NNR) was also calculated along with the number of articles retrieved by expert review. Cross-referencing from reviews and included articles also occurred. Results. Thirty-four of 36 articles (94.4%, 95% CI, 81.3–99.3) were located by database searching. PubMed and CENTRAL yielded 32 of 36 articles (88.9%, 73.9–96.9). Two articles not identified in any of the other databases were found in either CINAHL or SPORTDicsus. Two other articles were located by scanning the reference lists of review articles. The NNR ranged from 2 (CINAHL) to 118 (SPORTDiscus). More articles were identified in EMBASE at follow-up (36%, 12.1–42.2 versus 86.1%, 70.5–95.3). Conclusions. Searching multiple databases and cross-referencing from reviews was important for identifying RCTs addressing the effects of exercise on pain and physical function in adults with AORD.

AIM: To assess the safety and efficacy of carbon dioxide (CO2) insufflation during endoscopic retrograde cholangiopancreatography (ERCP).

METHODS: The Cochrane Library, Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Science Citation Index Expanded, Chinese Biomedical Literature Database, and references in relevant publications were searched up to December 2011 to identify randomized controlled trials (RCTs) comparing CO2 insufflation with air insufflation during ERCP. The trials were included in the review irrespective of sample size, publication status, or language. Study selection and data extraction were performed by two independent authors. The meta-analysis was performed using Review Manager 5.1.6. A random-effects model was used to analyze various outcomes. Sensitivity and subgroup analyses were performed if necessary.

RESULTS: Seven double-blind RCTs involving a total of 818 patients were identified that compared CO2 insufflation (n = 404) with air insufflation (n = 401) during ERCP. There were a total of 13 post-randomization dropouts in four RCTs. Six RCTs had a high risk of bias and one had a low risk of bias. None of the RCTs reported any severe gas-related adverse events in either group. A meta-analysis of 5 RCTs (n = 459) indicated that patients in the CO2 insufflation group had less post-ERCP abdominal pain and distension for at least 1 h compared with patients in the air insufflation group. There were no significant differences in mild cardiopulmonary complications [risk ratio (RR) = 0.43, 95% CI: 0.07-2.66, P = 0.36], cardiopulmonary (e.g., blood CO2 level) changes [standardized mean difference (SMD) = -0.97, 95% CI: -2.58-0.63, P = 0.23], cost analysis (mean difference = 3.14, 95% CI: -14.57-20.85, P = 0.73), and total procedure time (SMD = -0.05, 95% CI: -0.26-0.17, P = 0.67) between the two groups.

CONCLUSION: CO2 insufflation during ERCP appears to be safe and reduces post-ERCP abdominal pain and discomfort.

Background

The attachment of a transparent hood to the colonoscope tip has been reported to offer some benefits, such as enabling the endoscopist to perform the colonoscopy more easily and to save time. However, there have been no randomized, controlled trials concerning these benefits, nor have any reports been published regarding the use of hoods for the purpose of training colonoscopists. Therefore, we conducted this study to evaluate the possible benefits of the transparent soft short hood when used by both experienced and trainee endoscopist groups.

Methods

This randomized, controlled trial to assess the results of using a transparent soft short hood attached to the tip of the colonoscope was undertaken by two groups of investigators: experienced endoscopists and gastroenterologist trainees. The cecal and ileal intubation times, as well as the doses of sedative medication required, were analyzed.

Results

A total of 112 patients, 65 of whom were female, underwent colonoscopy by 2 endoscopists and 5 gastroenterologist trainees. Colonoscopy was complete in 100% of the patients. The study showed significant shortening of the cecal intubation time when using the soft short hood, in both the endoscopist and gastroenterologist trainee groups (6.8/4.61 min, P = 0.006; and 9.36/7.36 min, P = 0.03). The ileal intubation time had a trend to be significantly less when using the transparent hood in the trainee group (126.4/52.9 s), although this was not statistically significant (P = 0.08). The average dose of propofol, when using the transparent hood, was significantly lower in the endoscopist group (180/120 mg, P = 0.001). No significant complications occurred in the hood or non-hood groups.

Conclusions

The transparent soft short hood shortened the cecal intubation time in both the experienced endoscopist and gastroenterologist trainee groups, as well as reducing the dose of sedative medication required in the experienced endoscopist group. Interestingly, it also reduced the trainee ileal intubation time. The attachment of this type of hood enabled both the experienced endoscopists and gastroenterological trainees to perform colonoscopy more quickly and easily, without any complications.

Background

Glucocorticoids are often used in the treatment of nonhematologic malignancy. This review summarizes the clinical evidence of the effect of glucocorticoid therapy on nonhematologic malignancy.

Methods

A systematic review of clinical studies of glucocorticoid therapy in patients with nonhematologic malignancy was undertaken. Only studies having endpoints of tumor response or tumor control or survival were included. PubMed, EMBASE, the Cochrane Register/Databases, conference proceedings (ASCO, AACR, ASTRO/ASTR, ESMO, ECCO) and other resources were used. Data was extracted using a standard form. There was quality assessment of each study. There was a narrative synthesis of information, with presentation of results in tables. Where appropriate, meta-analyses were performed using data from published reports and a fixed effect model.

Results

Fifty four randomized controlled trials (RCTs), one meta-analysis, four phase l/ll trials and four case series met the eligibility criteria. Clinical trials of glucocorticoid monotherapy in breast and prostate cancer showed modest response rates. In advanced breast cancer meta-analyses, the addition of glucocorticoids to either chemotherapy or other endocrine therapy resulted in increased response rate, but not increased survival. In GI cancer, there was one RCT each of glucocorticoids vs. supportive care and chemotherapy +/- glucocorticoids; glucocorticoid effect was neutral. The only RCT found of chemotherapy +/- glucocorticoids, in which the glucocorticoid arm did worse, was in lung cancer. In glucocorticoid monotherapy, meta-analysis found that continuous high dose glucocorticoids had a detrimental effect on survival. The only other evidence, for a detrimental effect of glucocorticoid monotherapy, was in one of the two trials in lung cancer.

Conclusion

Glucocorticoid monotherapy has some benefit in breast and prostate cancer. In advanced breast cancer, the addition of glucocorticoids to other therapy does not change the long term outcome. In GI cancer, glucocorticoids most likely have a neutral effect. High dose continuous glucocorticoids have a detrimental effect in nonhematologic malignancy. Glucocorticoid therapy might have a deleterious impact in lung cancer.

The aim of this study was to compare the efficacy and safety of tigecycline, a newly developed glycylcycline antibiotic, with those of empirical antibiotic regimens which have been reported to possess good efficacy for complicated skin and skin structure infections (cSSSIs), complicated intra-abdominal infections (cIAIs), community-acquired pneumonia (CAP), and other infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). A meta-analysis of randomized controlled trials (RCTs) identified in PubMed, the Cochrane Library, and Embase was performed. Eight RCTs involving 4,651 patients were included in the meta-analysis. Compared with therapy with empirical antibiotic regimens, tigecycline monotherapy was associated with similar clinical treatment success rates (for the clinically evaluable [CE] population, odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.76 to 1.12, P = 0.42; for the clinical modified intent-to-treat [c-mITT] population, OR = 0.86, 95% CI = 0.74 to 1.01, P = 0.06) and similar microbiological treatment success rates (for the microbiologically evaluable [ME] population, OR = 0.86, 95% CI = 0.69 to 1.07, P = 0.19). The incidence of adverse events in the tigecycline group was significantly higher than that in the other therapy groups with a statistical margin (for the modified intent-to-treat [mITT] population, OR = 1.33, 95% CI = 1.17 to 1.52, P < 0.0001), especially in the digestive system (mITT population, OR = 2.41, 95% CI = 1.67 to 3.46, P < 0.00001). No difference regarding all-cause mortality and drug-related mortality between tigecycline and the other regimens was found, although numerically higher mortality was found in the tigecycline group. This meta-analysis provides evidence that tigecycline monotherapy may be used as effectively as the comparison therapy for cSSSI, cIAIs, CAP, and infections caused by MRSA/VRE. However, because of the high risk of mortality, AEs, and emergence of resistant isolates, prudence with the clinical use of tigecycline monotherapy in infections is required.