Low Self-Reported Function Predicts Adverse Postoperative Course in Veterans Affairs Beneficiaries Undergoing Total Hip and Total Knee Replacement.

OBJECTIVES: To measure association between self-reported function and an adverse postoperative course and improvement in performance on the American College of Surgeons Universal Risk Calculator (ACS calculator) with inclusion of self-reported function available through the Veteran Rand-12 based Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. DESIGN: Cohort analysis. SETTING: Veteran Affairs health system. PARTICIPANTS: Surgeries (n = 3,503) for older male veterans undergoing hip and knee replacement from 2002 to 2009. MEASUREMENTS: Serious complication (per ACS definition), discharge to facility, readmission, and death within 30 days after surgery as a function of PCS and MCS; comparison of prediction of net reclassification index (NRI) for serious complication using a modified version of the ACS calculator with prediction using the ACS calculator with MCS and PCS added. RESULTS: Being in the lowest PCS quartile (vs highest quartile) predicted more than twice the risk of a serious complication (odds ratio (OR) = 2.27, 95% confidence interval (CI) = 1.44-3.58), twice the risk of discharge to facility (OR = 1.97, 95% CI = 1.39-2.79), and almost twice the risk of readmission (OR = 1.80, 95% CI = 1.37-2.36). The lowest quartile of MCS predicted each outcome, although to a lesser extent than PCS. The enhanced model had a NRI of 29.4% (95% CI = 15.4-43.3%), reflecting that 20.8% of events were appropriately upgraded and 8.6% of nonevents appropriately downgraded. CONCLUSION: Low PCS and MCS predicted an adverse postoperative course and enhanced the ACS calculator. Clinicians evaluating older adults undergoing orthopedic surgery could enhance the accuracy of their assessments by including self-reported functional status.

Venous thromboembolism after joint replacement in older male veterans with comorbidity.

OBJECTIVES: To identify older adults with comorbidities or poor functional status at high risk of postoperative venous thromboembolism (VTE). DESIGN: Retrospective cohort study. SETTING: Veterans Affairs Medical Center (VAMC). PARTICIPANTS: Older adults who underwent total hip and knee replacement (THR and TKR) from 2002 to 2009. MEASUREMENTS: Using multivariate logistic regression, the independent effect of cardiopulmonary comorbidities and diabetes on VTE was analyzed. Functional status expressed in a summary physical component score (PCS) was also analyzed in a subset of individuals in whom information on it was available. RESULTS: There were 23,326 THR and TKR surgeries performed at the VAMC during the study period. Individuals with chronic obstructive pulmonary disease (COPD) had a 25% greater risk of VTE (odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.06-1.48), whereas those with coronary artery disease, congestive heart failure, and cerebrovascular disease did not have a greater risk of VTE. Individuals with diabetes mellitus had a lower risk of VTE (OR = 0.77, 95% CI = 0.64-0.92). Individuals with low PCS, which were available for 3,169 patients, had a 62% greater risk, although the effect did not reach statistical significance (lowest vs highest quartile OR = 1.62, 95% CI = 0.93-2.80). CONCLUSION: Individuals with COPD had slightly greater risk of VTE, whereas low functional status had a larger effect that did not reach statistical significance. The constraints of administrative data analysis and sample size available for PCS limit conclusions about the role of these comorbidities and functional status.

Comparison of in-hospital versus 30-day mortality assessments for selected medical conditions.

BACKGROUND: In-hospital mortality measures such as the Agency for Healthcare Research and Quality (AHRQ) Inpatient Quality Indicators (IQIs) are easily derived using hospital discharge abstracts and publicly available software. However, hospital assessments based on a 30-day postadmission interval might be more accurate given potential differences in facility discharge practices. OBJECTIVES: To compare in-hospital and 30-day mortality rates for 6 medical conditions using the AHRQ IQI software. METHODS: We used IQI software (v3.1) and 2004-2007 Veterans Health Administration (VA) discharge and Vital Status files to derive 4-year facility-level in-hospital and 30-day observed mortality rates and observed/expected ratios (O/Es) for admissions with a principal diagnosis of acute myocardial infarction, congestive heart failure, stroke, gastrointestinal hemorrhage, hip fracture, and pneumonia. We standardized software-calculated O/Es to the VA population and compared O/Es and outlier status across sites using correlation, observed agreement, and kappas. RESULTS: Of 119 facilities, in-hospital versus 30-day mortality O/E correlations were generally high (median: r = 0.78; range: 0.31-0.86). Examining outlier status, observed agreement was high (median: 84.7%, 80.7%-89.1%). Kappas showed at least moderate agreement (k > 0.40) for all indicators except stroke and hip fracture (k ≤ 0.22). Across indicators, few sites changed from a high to nonoutlier or low outlier, or vice versa (median: 10, range: 7-13). CONCLUSIONS: The AHRQ IQI software can be easily adapted to generate 30-day mortality rates. Although 30-day mortality has better face validity as a hospital performance measure than in-hospital mortality, site assessments were similar despite the definition used. Thus, the measure selected for internal benchmarking should primarily depend on the healthcare system's data linkage capabilities.

Trends in the inpatient quality indicators: the Veterans Health Administration experience.

BACKGROUND: The Agency for Healthcare Research and Quality Inpatient Quality Indicators (IQIs), which include in-hospital mortality and utilization rates, have received little attention in the Veterans Health Administration (VA), despite extensive private sector use for quality improvement. OBJECTIVES: We examined the following: the feasibility of applying the IQIs to VA data; temporal trends in national VA IQI rates; temporal and regional IQI trends in geographic areas defined by Veterans Integrated Service Networks' (VISNs); and VA versus non-VA (Nationwide Inpatient Sample) temporal trends. METHODS: We derived VA- and VISN-level IQI observed rates, risk-adjusted rates, and observed to expected ratios (O/Es), using VA inpatient data (2004-2007). We examined the trends in VA- and VISN-level rates using weighted linear regression, variation in VISN-level O/Es, and compared VA to non-VA trends. RESULTS: VA in-hospital mortality rates from selected medical conditions (stroke, hip fracture, pneumonia) decreased significantly over time; procedure-related mortality rates were unchanged. Laparoscopic cholecystectomy rates increased significantly. A few VISNs were consistently high or low outliers for the medical-related mortality IQIs. Within any given year, utilization indicators, especially cardiac catheterization and cholecystectomy, showed the most inter-VISN variation. Compared with the non-VA, VA medical-related mortality rates for the above-mentioned conditions decreased more rapidly, whereas laparascopic cholecystectomy rates rose more steeply. CONCLUSIONS: The IQIs are easily applied to VA administrative data. They can be useful to tracks rate trends over time, reveal variation between sites, and for trend comparisons with other healthcare systems. By identifying potential quality events related to mortality and utilization, they may complement existing VA quality improvement initiatives.

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.

Breastfeeding and maternal and infant health outcomes in developed countries.

OBJECTIVES: We reviewed the evidence on the effects of breastfeeding on short- and long-term infant and maternal health outcomes in developed countries. DATA SOURCES: We searched MEDLINE(R), CINAHL, and the Cochrane Library in November of 2005. Supplemental searches on selected outcomes were searched through May of 2006. We also identified additional studies in bibliographies of selected reviews and by suggestions from technical experts. REVIEW METHODS: We included systematic reviews/meta-analyses, randomized and non-randomized comparative trials, prospective cohort, and case-control studies on the effects of breastfeeding and relevant outcomes published in the English language. Included studies must have a comparative arm of formula feeding or different durations of breastfeeding. Only studies conducted in developed countries were included in the updates of previous systematic reviews. The studies were graded for methodological quality. RESULTS: We screened over 9,000 abstracts. Forty-three primary studies on infant health outcomes, 43 primary studies on maternal health outcomes, and 29 systematic reviews or meta-analyses that covered approximately 400 individual studies were included in this review. We found that a history of breastfeeding was associated with a reduction in the risk of acute otitis media, non-specific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, sudden infant death syndrome (SIDS), and necrotizing enterocolitis. There was no relationship between breastfeeding in term infants and cognitive performance. The relationship between breastfeeding and cardiovascular diseases was unclear. Similarly, it was also unclear concerning the relationship between breastfeeding and infant mortality in developed countries. For maternal outcomes, a history of lactation was associated with a reduced risk of type 2 diabetes, breast, and ovarian cancer. Early cessation of breastfeeding or not breastfeeding was associated with an increased risk of maternal postpartum depression. There was no relationship between a history of lactation and the risk of osteoporosis. The effect of breastfeeding in mothers on return-to-pre-pregnancy weight was negligible, and the effect of breastfeeding on postpartum weight loss was unclear. CONCLUSIONS: A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers from developed countries. Because almost all the data in this review were gathered from observational studies, one should not infer causality based on these findings. Also, there is a wide range of quality of the body of evidence across different health outcomes. For future studies, clear subject selection criteria and definition of "exclusive breastfeeding," reliable collection of feeding data, controlling for important confounders including child-specific factors, and blinded assessment of the outcome measures will help. Sibling analysis provides a method to control for hereditary and household factors that are important in certain outcomes. In addition, cluster randomized controlled studies on the effectiveness of various breastfeeding promotion interventions will provide further opportunity to investigate any disparity in health outcomes as a result of the intervention.

Hereditary nonpolyposis colorectal cancer: diagnostic strategies and their implications.

OBJECTIVES: Hereditary Nonpolyposis Colorectal Cancer (HNPCC) has been defined clinically and genetically. The disorder has traditionally been recognized in kindreds with a clustering of related cancers in association with mutations in DNA mismatch repair genes. HNPCC is associated with a substantially increased risk for several forms of malignancy but particularly colorectal and endometrial cancer. There were three main objectives of this report: (1) to assess the sensitivity, specificity, and reliability of laboratory and genetic tests commonly used in evaluating patients for HNPCC (analytic validity); (2) to summarize the accuracy of commonly used clinical and laboratory characteristics for predicting the presence of HNPCC in patients with colorectal cancer (clinical validity) and use these estimates to describe the efficiency of various strategies for identifying patients with a mismatch repair mutation; (3) to describe the benefits and harms related to screening and testing patients with colorectal cancer and their family members for HNPCC. DATA SOURCES: Published literature identified through an electronic search (through April 2006), review of relevant bibliographies, and suggestions from technical experts. REVIEW METHODS: We evaluated studies critically and summarized the data qualitatively or by meta-analysis when studies used similar methodology and endpoints. We used decision trees to describe the efficiency of various strategies for identifying patients with HNPCC from a hypothetical population of patients with colorectal cancer. RESULTS: We included a total of 104 studies of which 40 addressed issues related to clinical validity, 3 to analytic validity, and 61 to benefits and harms. We identified only three studies on analytic validity and thus there exists a major gap in the published literature with regard to the accuracy and reliability of specific tests used in the evaluation of HNPCC. Among unselected patients with colorectal cancer who fulfilled the Amsterdam I criteria, 44% (95% CI: 35, 52%) carried pathogenic mismatch repair mutations (mainly in the MLH1 and MSH2 genes). The proportion was somewhat higher (51% [95% CI: 35, 66%]) among studies that performed sequencing on all available samples. The prevalence of MMR mutation carriers may be higher when genetic testing includes evaluation for large genomic deletions/rearrangements and when testing is also performed on MSH6 and PMS2. Approximately 71% (95% CI 63, 78%) of colorectal cancers from patients who fulfilled the Amsterdam I criteria demonstrated microsatellite instability while 40% (95% CI: 28, 53%) demonstrated loss of protein expression by immunohistochemistry. Of nine clinical strategies considered for detecting the presence of mismatch repair mutations in patients with colorectal cancer, the combination of three clinical predictors (age less than 50 years old at diagnosis; or a history of colorectal or endometrial cancer in a first degree family member; or the presence of multiple, synchronous or metachronous colorectal or endometrial cancers in the proband) combined with either immunohistochemistry (IHC) or MSI testing of tumor tissue identified a similar number of patients with mismatch repair mutations as other more complex strategies. There was little published information regarding potential harms associated with screening individuals with HNPCC-related cancers using clinical criteria (e.g. the Amsterdam criteria), MSI or IHC testing. Limited data suggested that testing probands for MMR mutations was not associated with severe psychological impact following formal counseling. Pre-test genetic counseling had good efficacy in improving knowledge about HNPCC and resulted in a high likelihood of proceeding with genetic testing, satisfaction in the decision to undergo genetic testing, and decreasing depression and distress levels among family members of HNPCC probands with cancer and among asymptomatic individuals from HNPCC families. Identification of HNPCC mutations was associated with an increase in the likelihood that family members of probands with CRC would undergo cancer-screening procedures. HNPCC family members who underwent cancer-screening procedures had a lower risk of developing HNPCC-related cancers and lower mortality rates than those who did not take actions. However, all of the relevant studies suggesting these benefits had important limitations. Survival was increased among asymptomatic HNPCC family members who received colonoscopy screening, regardless of their mutation status. There was limited direct evidence related to harms of the cancer-screening procedures in family members of probands with HNPCC. However, complication rates associated with these procedures in other settings are probably similar. CONCLUSIONS: This report characterizes the accuracy of clinical and laboratory predictors of MMR mutations that can be used to identify patients with an increased risk of having MMR mutations. However, the sensitivity, specificity, and reliability of the tests used to evaluate individuals for suspected HNPCC is not known confidently. Data regarding the net benefits and harms associated with predictive genetic testing in patients with HNPCC-related cancers and their families members is incomplete but suggest that such testing improves compliance with screening procedures. At-risk family members who undergo screening colonoscopy have a reduced risk of developing HNPCC-related cancers and lower mortality. However, all studies supporting these benefits had important limitations.

Effectiveness of management strategies for renal artery stenosis: a systematic review.

BACKGROUND: Atherosclerotic renal artery stenosis is increasingly common in an aging population. Therapeutic options include medical treatment only or revascularization procedures. PURPOSE: To compare the effects of medical treatment and revascularization on clinically important outcomes in adults with atherosclerotic renal artery stenosis. DATA SOURCES: The MEDLINE database (inception to 6 September 2005) and selected reference lists were searched for English-language articles. STUDY SELECTION: The authors selected prospective studies of renal artery revascularization or medical treatment of patients with atherosclerotic renal artery stenosis that reported mortality rates, kidney function, blood pressure, cardiovascular events, or adverse events at 6 months or later after study entry. DATA EXTRACTION: A standardized protocol with predefined criteria was used to extract details on study design, interventions, outcomes, study quality, and applicability. The overall body of evidence was then graded as robust, acceptable, or weak. DATA SYNTHESIS: No study directly compared aggressive medical therapy with angioplasty and stent placement. Two randomized trials compared angioplasty without stent and medical treatments. Eight other comparative studies and 46 cohort studies met criteria for analysis. Studies generally had poor methodologic quality and limited applicability to current practice. Overall, there was no robust evidence. Weak evidence suggested no large differences in mortality rates or cardiovascular events between medical and revascularization treatments. Acceptable evidence suggested similar kidney-related outcomes but better blood pressure outcomes with angioplasty, particularly in patients with bilateral disease. Improvements in kidney function and cure of hypertension were reported among some patients only in cohort studies of angioplasty. Available evidence did not adequately assess adverse events or baseline characteristics that could predict which intervention would result in better outcomes. LIMITATIONS: The evidence from direct comparisons of interventions is sparse and inadequate to draw robust conclusions. CONCLUSIONS: Available evidence does not clearly support one treatment approach over another for atherosclerotic renal artery stenosis.

Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review.

Greater fish oil consumption has been associated with reduced CVD risk, although the mechanisms are unclear. Plant-source oil omega-3 fatty acids (ALA) have also been studied regarding their cardiovascular effect. We conducted a systematic review of randomized controlled trials that evaluated the effect of consumption of fish oil and ALA on commonly measured serum CVD risk factors, performing meta-analyses when appropriate. Combining 21 trials evaluating lipid outcomes, fish oil consumption resulted in a summary net change in triglycerides of -27 (95% CI -33, -20)mg/dL, in HDL cholesterol of +1.6 (95% CI +0.8, +2.3)mg/dL, and in LDL cholesterol of +6 (95% CI +3, +8)mg/dL. There was no effect of fish oil on total cholesterol. Across studies, higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides. Overall, the 27 fish oil trials evaluating Hgb A(1c) or FBS found small non-significant net increases compared to control oils. Five studies of ALA were inconsistent in their effects on lipids, Hgb A(1c) or FBS. Four studies investigating the effects of omega-3 fatty acids on hs-CRP were also inconsistent and non-significant. The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels. Fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis. The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive, as are data on ALA.

Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review.

Greater omega-3 fatty acid consumption is associated with reduced cardiovascular disease risk. Though the mechanisms of their effect are unclear, they may involve lesion formation and heart function. We conducted a systematic review of the clinical literature on the effect of omega-3 fatty acids on measures of vascular structure and function. We included studies that assessed fish and plant sources of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid IMT, and exercise capacity. Compared to placebo, the summary risk ratio of coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12 randomized controlled trials. Two prospective studies reported increased carotid IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish, fish oil or ALA consumption. Three randomized trials and three uncontrolled studies reported small non-significant improvements in exercise capacity with fish oil. Overall, little or no effect of fish oil was found for a variety of markers of cardiovascular disease risk. There are insufficient studies to draw conclusions about the effect of ALA. The dearth of long term data on fish consumption or omega-3 fatty acid supplementation on measures of cardiovascular disease risk severely limits our ability to draw definitive conclusions at this time.

B vitamins and berries and age-related neurodegenerative disorders.

OBJECTIVES: To assess the effects, associations, mechanisms of action, and safety of B vitamins and, separately, berries and their constituents on age-related neurocognitive disorders-primarily Alzheimer's (AD) and Parkinson's disease (PD). DATA SOURCES: MEDLINE and CAB Abstracts. Additional studies were identified from reference lists and technical experts. REVIEW METHODS: Vitamins B1, B2, B6, B12, and folate, and a dozen types of berries and their constituents were evaluated. Human, animal, and in vitro studies were evaluated. Outcomes of interest from human studies were neurocognitive function or diagnosis with AD, cognitive decline, PD, or related conditions. Intervention studies, associations between dietary intake and outcomes, and associations between B vitamin levels and outcomes were evaluated. Specific mechanisms of action were evaluated in animal and in vitro studies. Studies were extracted for study design, demographics, intervention or predictor, and neurocognitive outcomes. Studies were graded for quality and applicability. RESULTS: In animal studies, deficiencies in vitamins B1 or folate generally cause neurological dysfunction; supplementation with B6, B12, or folate may improve neurocognitive function. In animal experiments folate and B12 protect against genetic deficiencies used to model AD; thiamine and folate also affect neurovascular function and health. Human studies were generally of poor quality. Weak evidence suggests possible benefits of B1 supplementation and injected B12 in AD. The effects of B6 and folate are unclear. Overall, dietary intake studies do not support an association between B vitamin intake and AD. Studies evaluating B vitamin status were mostly inadequate due to poor study design. Overall, studies do not support an association between B vitamin status and age-related neurocognitive disorders. Only one study evaluated human berry consumption, finding no association with PD. Animal studies of berries have almost all been conducted by the same research group. Several berry constituents have been shown to affect brain and nerve tissue function. Blueberry and strawberry extract were protective of markers of disease, although effects on neurocognitive tests were less consistent. Berry extracts may protect against the deleterious effects of compounds associated with AD. Reporting of adverse events was uncommon. When reported, actual adverse events from B vitamins were rare and minor. CONCLUSIONS: The current research on B vitamins is largely inadequate to confidently assess their mechanisms of action on age-related neurocognitive disorders, their associations with disease, or their effectiveness as supplements. B vitamin supplementation may be of value for neurocognitive function, but the evidence is inconclusive.

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.

Effects of statins on vascular structure and function: a systematic review.

PURPOSE: Statins reduce cardiovascular events by more than can be explained by their effects on lipids. We conducted a systematic review of how statins affect vascular structure and function, differences among statins, and correlations between the effects of statins on vascular outcomes and either lipid levels or cardiovascular outcomes. METHODS: We primarily searched MEDLINE (1980 to March 2004) to identify all studies with at least 10 subjects that reported the effects of currently available statins on coronary artery stenosis, carotid intima-media thickness, and endothelial function (excluding studies of drug combinations and subjects with organ transplants). Meta-analyses were performed when feasible. RESULTS: Statins decrease the progression and increase the regression of coronary artery lesions and luminal narrowing. Compared with placebo, statins decrease the likelihood of coronary artery restenosis (summary risk ratio = 0.85; 95% confidence interval: 0.77 to 0.95). Statins appear to slow the progression of carotid artery intima-media thickness. Although the effect of statins on coronary endothelial function is uncertain, statins appear to improve peripheral endothelial function. There is no conclusive evidence to suggest that individual statins differ in their effects on these outcomes. Studies generally found weak or no correlation between the effects of statins on vascular outcomes and lipid levels. No study showed a correlation between vascular effect and clinical outcome. CONCLUSION: Statins slow the progression of, and may reverse, atherosclerosis. The magnitude of these effects, however, is small compared with the effects of statins on cardiovascular events. Statins also improve measures of vascular function, which may contribute to their clinical benefits. There is insufficient evidence to suggest that individual statins differ in their vascular effects.

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.

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.