Priscilla Chew

Management of opioid side effects in cancer-related and chronic noncancer pain: a systematic review ☆

Side effects can limit opioid dosage and reduce quality of life. The purpose of this systematic review was to assess the management of opioid side effects in the context of cancer pain management or, in the event that no evidence was available for cancer pain, for chronic noncancer pain. The side effects studied were constipation, pruritus, nausea and vomiting, myoclonus, sedation, respiratory depression, and delirium. Opioid rotation to manage side effects was also studied. For each side effect, we searched MEDLINE and the Cochrane Controlled Trials Register and identified 657 possible titles for inclusion. Of these, 67 studies met inclusion criteria for analysis. The lack of well-designed, randomized controlled trials and the heterogeneity of populations and study designs made the drawing of firm conclusions difficult and precluded performance of meta-analysis. The type, strength, and consistency of evidence for available interventions to manage opioid side effects vary from strong (eg, on the use of naloxone to reverse respiratory depression or constipation) to weak (eg, changing from the oral to epidural route of morphine administration to manage sedation). Well-designed trials in the specified populations are required to furnish clinicians with secure evidence on managing opioid side effects successfully.

Effectiveness of Management Strategies for Renal Artery Stenosis: A Systematic Review

Context Is medical therapy as effective as revascularization for atherosclerotic renal artery stenosis? Contribution This systematic review found no trials that compared aggressive medical therapy and angioplasty with stent in adults with atherosclerotic renal artery stenosis. Some evidence suggested similar kidney outcomes but better blood pressure outcomes with angioplasty, particularly in patients with bilateral renal disease. Weak evidence suggested no large differences in mortality or cardiovascular events between medical and revascularization treatments. No evidence directly compared adverse event rates between treatments. Implications Available evidence comparing benefits and harms of modern treatments for atherosclerotic renal artery stenosis is sparse and inconclusive. The Editors Renal artery stenosis is defined as narrowing of the renal artery lumen. Atherosclerosis, which usually involves the ostium and proximal third of the main renal artery and the perirenal aorta, accounts for 90% of cases of renal artery stenosis (1). Atherosclerotic renal artery stenosis is increasingly common in aging populations, particularly elderly people with diabetes, hyperlipidemia, aortoiliac occlusive disease, coronary artery disease, or hypertension. Atherosclerotic renal artery stenosis is a progressive disease that may occur alone or in combination with hypertension and ischemic kidney disease (1). Although the prevalence of atherosclerotic renal artery stenosis is poorly defined, it may vary from 30% among patients with coronary artery disease identified by angiography (2) to 50% among elderly people or those with diffuse atherosclerotic vascular diseases (3). In the United States, 12% to 14% of patients in whom dialysis is initiated have been found to have atherosclerotic renal artery stenosis (4). Most authorities consider blood pressure control, preservation or salvage of kidney function, and prevention of flash pulmonary edema to be important treatment goals for patients with atherosclerotic renal stenosis. Treatment options include medication alone or revascularization of the stenosed artery or arteries. Combination therapy with multiple antihypertensive agents, often including angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium-channel blockers, and -blockers, is frequently prescribed. Some clinicians also use statins to decrease low-density lipoprotein cholesterol levels and antiplatelet agents, such as aspirin or clopidogrel, to reduce the risk for thrombosis. The current standard for revascularization in most patients is percutaneous transluminal angioplasty with stent placement across the stenosis. Angioplasty without stent placement is less commonly used. Revascularization by surgical reconstruction is generally done only in patients with complicated renal artery anatomy or in those who require pararenal aortic reconstructions for aortic aneurysms or severe aortoiliac occlusive disease. The American College of Cardiology and the American Heart Association recently published guidelines for management of patients with peripheral arterial disease, including renal artery stenosis (5, 6). Although these guidelines provide recommendations about which patients should be considered for revascularization, considerable uncertainty remains about which intervention provides the best clinical outcomes. Among patients treated with medical therapy alone, experts are concerned about the risk for deterioration of kidney function and worsening cardiovascular morbidity and mortality. Revascularization procedures may provide immediate improvement in kidney function and blood pressure, but they are invasive interventions that could result in substantial morbidity or death, and because of the risk for restenosis the durability of their benefits is questioned. Although evidence regarding the optimal management of atherosclerotic renal artery stenosis appears uncertain, a Medicare claims analysis found that the rate of percutaneous renal artery revascularization has rapidly increased between 1996 and 2000, with the number of interventions increasing from 7660 to 18520 (7). To determine which patients, if any, with atherosclerotic renal artery stenosis would most benefit from angioplasty with stent placement, as opposed to continued aggressive medical treatment, the National Institutes of Health has sponsored the large, multicenter Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial. Participants are currently being enrolled in the trial, and results should be reported in 2010. Meanwhile, the Agency for Healthcare Research and Quality, under Section 1013 of the Medicare Modernization Act, commissioned a review asking key questions related to the effectiveness of aggressive medical therapy compared with renal artery angioplasty with stent placement. However, because no published evidence directly compared angioplasty with stent placement and aggressive medical treatment with currently available drugs, the review covered direct comparisons of revascularization, including angioplasty with or without stent placement and surgery, and various medical regimens and indirect comparisons of angioplasty (with stent placement) and surgical interventions, various medical therapies, and natural history (8). Methods Data Sources and Selection To identify articles relevant to several key questions, we searched the MEDLINE database from inception to 6 September 2005 for studies involving adults with atherosclerotic renal artery stenosis. The Figure shows the search and selection process. The full technical report (available at www.effectivehealthcare.ahrq.gov/reports/final.cfm) provides a more detailed description of the study methods. We also reviewed reference lists of related systematic reviews, selected narrative reviews, and primary articles, and we invited domain experts to provide additional citations. We combined search terms for renal artery stenosis, renal hypertension, and renal vascular disease, and we limited the search to English-language articles of studies in adult humans that had relevant research designs. We included peer-reviewed primary studies of adult patients treated for atherosclerotic renal artery stenosis and excluded studies that evaluated patients with renal artery stenosis in the setting of a transplanted kidney, renal artery aneurysm requiring repair, aortic disease requiring invasive intervention, or concurrent cancer or patients who had had previous surgical or angioplasty interventions for renal artery stenosis. We included only studies that reported outcomes of interest (mortality rate, kidney function, blood pressure, and cardiovascular events) at 6 months or more after the initial intervention. We excluded studies in which more than 20% of patients had renal artery stenosis due to other causes. We categorized studies according to whether they evaluated medical treatment, angioplasty, or surgical revascularization or were natural history studies, and by whether they directly compared interventions. Figure. Search and selection of studies for review. *Prospective study; enrolled 10 or more patients; study duration at least 6 months. Prospective study; angioplasty included stent placement; enrolled 30 or more patients; study duration at least 6 months; patients recruited in 1993 or later; patients did not have previous angioplasty. One study has data both for direct comparison of medical treatment to angioplasty and for natural history. Any study design; enrolled 10 or more patients; study duration at least 6 months. Studies with surgical intervention must have recruited patients in 1993 or later. Any study design; enrolled 10 or more patients; study duration at least 6 months; patients recruited in 1993 or later. Any study design; enrolled 100 or more patients (10 or more if the study was prospective); study duration at least 6 months; patients recruited in 1993 or later. We used different eligibility criteria for studies of different interventions, based on the varying number of studies available for each intervention and the relevance of the intervention to current practice. We included all direct comparisons of medical treatment with angioplasty and all uncontrolled (cohort) studies of medical treatment that had at least 10 patients in each group, regardless of study design. For angioplasty, surgical, or natural history studies, we included only those in which at least some patients were recruited in 1993 or later, after the publication of the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. These guidelines marked a substantial change from previous guidelines in treatment recommendations for hypertension, including more aggressive blood pressure targets (9). In addition, at this time point, angiotensin-converting enzyme inhibitors began to be used more routinely in the treatment of patients with severe hypertension. We included only angioplasty studies that used stent placement, were prospective, and had at least 30 patients and retrospective surgery studies that included at least 100 patients. Any prospective surgery study that otherwise met criteria was eligible. Data Extraction and Quality and Applicability Assessments Data from each study were extracted by one of the authors and confirmed by another. The extracted data included information about patient samples, interventions, outcomes, adverse events, study design, quality, and applicability. We used predefined criteria to grade study quality as good, fair, or poor; study applicability as high, moderate, or low; and the strength of the overall body of evidence as robust, acceptable, or weak (Appendix Table). Each included study was graded by at least 2 of the authors. Appendix Table. Study Quality, Applicability, and Strength of Evidence Ratings Data Synthesis Because the study designs, participants, interventions, and reported outcome measures varied marke

Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections

We carried out a meta-analysis of randomized controlled trials comparing 3-5 days of azithromycin with other antibiotics that are typically given in longer courses for the treatment of upper respiratory tract infections. For acute otitis media (19 comparisons including 3421 patients), acute sinusitis (11 comparisons including 1742 patients) and acute pharyngitis (16 comparisons including 2447 patients), azithromycin had similar clinical failure rates to the other antibiotics [random effects odds ratios 1.12, 95% confidence interval (CI) 0.81-1.54; 0.91, 95% CI 0.60-1.39; and 1.07, 95% CI 0.59-1.94, respectively]. The difference in clinical failures was <0.5%, and no 95% CIs exceeded 2.0%. There was no heterogeneity between studies. Subtle differences between comparators could have been due to chance. There were no significant differences in bacteriological outcomes. Azithromycin was discontinued because of adverse events in only 37 of 4870 (0.8%) patients. Short courses of azithromycin are as effective as longer courses of other antibiotics for upper respiratory tract infections. Convenience of dosing should be balanced against the increased cost of this regimen for the treatment of these common infections, where often no antibiotic may be indicated at all.

Standardized retrieval of side effects data for meta-analysis of safety outcomes. A feasibility study in acute sinusitis.

Accurate and complete safety data are indispensable for the proper evaluation of the benefit-to-harm ratio of medical interventions. We evaluated whether a systematic review and meta-analysis of standardized safety data is feasible by requesting information on side effects directly from the investigators of all 38 antibiotic trials on acute sinusitis published in the last decade. We requested standardized information on gastrointestinal toxicity outcomes, including hospitalizations, discontinuations, and days with nausea/vomiting, diarrhea, or both. Responses were received only for 16 trials (42%), and safety data were contributed only for 9 trials (24%). In some trials, safety data had not been collected, had been lost, or had been transferred to other companies. The odds of data retrieval was higher in general medical journals (P =.024) and independently improved with an increase in sample size (P =.064). The available information suggested side effects may equal or exceed in severity the marginal treatment benefits. Interpretation of safety data was further complicated by heterogeneity or lack of information of use of concomitant drugs, mode of collection of safety information, use of blinding, and other study design parameters. Availability of standardized information for performing meta-analysis of safety data may be limited. Standardized reporting, prospective collection, and long-term availability of safety information should be improved.

Effects of Fish Oil Supplementation on Kidney Transplantation: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials

The objective of this study was to assess the effects of omega-3 fatty acid supplementation on various kidney transplant-related outcomes. A systematic review and meta-analysis was performed of published randomized, controlled trials (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No consistent benefits were observed for any outcome with the exception of a modest benefit on triglycerides. A meta-analysis of rejection episodes found no significant benefit on either early (<6 mo posttransplantation) or late episodes. The overall relative risk of having at least one rejection episode in those who received fish oil was 0.91 (95% confidence interval 0.74 to 1.10) in four studies with a follow-up of 1 yr. A meta-analysis of eight RCT of graft survival found no significant benefit (relative risk 1.00, 95% confidence interval 0.96 to 1.05). The available data (mostly derived from older studies with important methodologic limitations) do not demonstrate a consistent, clinically important benefit of fish oil in kidney transplantation.

Predictors of clinical outcomes following fundoplication for gastroesophageal reflux disease remain insufficiently defined: a systematic review.

OBJECTIVES:Surgical treatment is a therapeutic option for patients with gastroesophageal reflux disease (GERD). It is unclear which patient characteristics influence postoperative success. The purpose of this paper was to review the literature on prognostic factors for patients with GERD treated with fundoplication.METHODS:We searched Medline and the Cochrane Library Central for studies from 1966 through July 2007. We identified additional studies by reviewing bibliographies of retrieved articles and by consulting experts. We included English language studies that evaluated factors potentially affecting the outcomes after surgical treatments in patients with GERD. We recorded baseline patient characteristics associated with treatment efficacy, details on the study design, comparators, and definitions of outcomes.RESULTS:We assessed 6,318 abstracts; 53 cohorts and 10 case–control studies met our inclusion criteria. Age, body mass index, sex, esophagitis grade, and dysmotility were generally not associated with treatment outcomes. There were no consistent associations between preoperative response to acid suppression medications, baseline symptoms, baseline acid exposure, degree of lower esophageal sphincter competence, or position of reflux and surgical outcomes. Certain psychological factors might be associated with worse treatment outcomes.CONCLUSIONS:Although several preoperative predictors of surgical outcomes have been described, the quality and consistency of the data were mixed and the strength of the associations remains unclear. Additional studies with improved methodological designs are needed to better define which patient characteristics are associated with surgical outcomes following fundoplication.