Gowri Raman

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

A Summary of the Agency for Healthcare Research and Quality's Evidence Report on Breastfeeding in Developed Countries

OBJECTIVES This article summarizes the Agency for Healthcare Research and Qualitys evidence report on the effects of breastfeeding on term infant and maternal health outcomes in developed countries. EVIDENCE REPORT DATA SOURCES Medline, CINAHL, Cochrane Library, bibliographies of selected reviews, and suggestions from domain experts were surveyed. Searches were limited to English-language publications. EVIDENCE REPORT REVIEW METHODS Eligible comparisons examined the association between differential exposure to breastfeeding and health outcomes. We assessed 15 infant and six maternal outcomes. For four outcomes, we also updated previously published systematic reviews. For the rest of the outcomes, we either summarized previous systematic reviews or conducted new systematic reviews; randomized and non-randomized comparative trials, prospective cohorts, and case-control studies were included. Adjusted estimates were extracted from non-experimental designs. The studies were graded for methodological quality. We did not draw conclusions from poor quality studies. EVIDENCE REPORT RESULTS We screened over 9,000 abstracts. Thirty-two primary studies on term infant health outcomes, 43 primary studies on maternal health outcomes, and 28 systematic reviews or meta-analyses that covered approximately 400 individual studies were included in this review. A history of breastfeeding was associated with a reduction in the risk of acute otitis media, nonspecific gastroenteritis, severe lower respiratory tract infections, atopic dermatitis, asthma (young children), obesity, type 1 and 2 diabetes, childhood leukemia, and sudden infant death syndrome. There was no relationship between breastfeeding in term infants and cognitive performance. There were insufficient good quality data to address the relationship between breastfeeding and cardiovascular diseases and infant mortality. 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 no 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-prepregnancy weight was negligible, and the effect of breastfeeding on postpartum weight loss was unclear. EVIDENCE REPORT CONCLUSIONS A history of breastfeeding is associated with a reduced risk of many diseases in infants and mothers. Future research would benefit from clearer selection criteria, definitions of breastfeeding exposure, and adjustment for potential confounders. Matched designs such as sibling analysis may provide a method to control for hereditary and household factors that are important in certain outcomes.

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

Angiotensin-Converting Enzyme Insertion/Deletion Gene Polymorphic Variant as a Marker of Coronary Artery Disease: A Meta-analysis

BACKGROUND Many studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphic variant and coronary artery disease (CAD). However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous samples. To shed light on these inconclusive findings, we conducted a meta-analysis of studies relating the ACE I/D polymorphic variant to the risk of CAD. METHODS We searched the PubMed database for English-language articles on CAD in humans. We estimated summary odds ratios and explored potential sources of heterogeneity and bias. RESULTS The 118 studies chosen for the analysis involved 43 733 cases with CAD and 82 606 controls. The heterogeneity between studies was significant. When we compared homozygotes with the D and I alterations, the ACE I/D polymorphic variant was associated with a 25% increased risk of CAD (odds ratio, 1.25; 95% confidence interval, 1.16-1.35). Subgroup analyses for myocardial infarction, diabetes mellitus, male sex, white race, East Asian subjects, and Turkish subjects showed significant associations. No association was found in other racial/ethnic groups, in women, in premature cases, or in cases with low levels of risk factors. The major sources of heterogeneity were due to racial/ethnic diversity, genotyping procedure, and age matching. Cumulative meta-analysis for the allelic contrast showed a trend of association as information accumulated. There was a differential magnitude of effect in large vs small studies. CONCLUSIONS The meta-analysis demonstrated evidence of a modest positive association between ACE I/D polymorphic variant and CAD. The meta-analysis also highlights the heterogeneity of reported results, considerable gaps in research, and the need for future studies focused on certain high-risk patient populations.

Systematic review: reliability of compendia methods for off-label oncology indications.

The U.S. Food and Drug Administration (FDA) approves drugs for specific uses, yet physicians routinely prescribe FDA-approved drugs for uses other than those for which they received approval (1); such uses are known as off-label indications. Off-label prescribing is common across medical disciplines; however, it is critical in oncology, in which effective treatment options are often limited, prognoses are grim, and submission of FDA applications for every combination of agent and cancer is impractical. In 1991, a U.S. General Accounting Office study (2) reported that up to 33% of all anticancer drug prescriptions were written for off-label indications. By 2005, the National Comprehensive Cancer Network estimated that 50% to 75% of all uses of cancer therapy were off-label (3). The Social Security Act, section 1861(t)(2)(B)(ii)(I) and (II), within the Omnibus Budget Reconciliation Act of 1993 (4), stipulates the Medicare insurability of anticancer drugs and biologics for off-label uses. This statute recognizes certain compendia as authoritative sources for determining a medically accepted indication of drugs and biological agents, unless the Secretary of Health and Human Services determines otherwise. The statute originally designated 3 compendia: American Medical Association Drug Evaluations, American Hospital Formulary Service Drug Information (5), and United States Pharmacopeia Drug Information for the Health Professional (6). Although the statute pertained specifically to Centers for Medicare & Medicaid Services (CMS), most other payers and state legislatures have followed suit (7). The list of approved compendia has shifted over the past 15 years. American Medical Association Drug Evaluations was discontinued, and United States Pharmacopeia Drug Information for the Health Professional subsumed its contents. United States Pharmacopeia Drug Information for the Health Professional was then discontinued in 2007, and its contents were rolled into a successor, DrugPoints. In 2008, CMS added Clinical Pharmacology, DRUGDEX, and National Comprehensive Cancer Network Drugs and Biologics Compendium to its list of approved compendia, bringing the total to 5 (8). In response to concerns about the influence of compendia, CMS proposed various changes, including review of currently approved compendia, additional compendia approval, and an annual review process. To inform policy discussions, they commissioned the Agency for Healthcare Research and Quality to sponsor our project exploring the extent to which compendia provide comprehensive, evidence-based, and timely information for guiding off-label prescribing of cancer drugs. Methods Our study had 4 components: comparative descriptions of each compendiums stated methods for including new, off-label indications of FDA-approved drugs; systematic literature review for 14 selected off-label indications in 2006; an updated comparison for 1 indication in 2008; and analysis of each compendiums content and citations against their stated methods and the evidence identified in our systematic reviews. Comparative Description of Methods Used by Compendia To better understand how compendia develop their content, we compared 6 compendia that we chose through discussions with 10 oncology pharmacists and oncologists at Duke University and Tufts Medical Centers. We confirmed the list through discussions with the Agency for Healthcare Research and Quality, CMS, and financial officers at Duke University Medical Center. Our final compendia list included American Hospital Formulary Service Drug Information (5), United States Pharmacopeia Drug Information for the Health Professional (6), DRUGDEX Information System (United States Pharmacopeia Drug Information for the Health Professional and DRUGDEX, both available through Thomson Reuters) (9), Drug Facts and Comparisons (10), National Comprehensive Cancer Network Drugs and Biologics Compendium (11), and Clinical Pharmacology (12). This list includes the compendia approved by CMS as well as 2 nonapproved compendia. These compendia list more than 40000 drugs, and their editors are generally pharmacologists with training in research and evidence synthesis. In 2006, we gathered information on each compendiums methods by abstracting descriptive information from publicly available sources, conducting a 1-hour telephone interview with a senior editor from each compendium, and allowing the editors to respond to a methods table that summarized the information collected in the interview. We developed a list of evaluation criteria which we used to compare published methods and guide interviews. We then compared each compendiums methods with evaluation criteria and summarized the results. In 2008, we repeated the data abstraction to determine whether the compendia had updated their publicized methods. We did not include DrugPoints in the 2008 review because it differed structurally from the other compendia and could not be directly compared. Literature Review of Evidence for 14 Off-Label Indications We selected off-label indications for 14 agent and cancer combinations that included both newer and older agents, common and rare types of cancer, and biologics and drugs. In 2006, we systematically searched MEDLINE, the Cochrane Central Register of Controlled Trials, and American Society of Clinical Oncology annual meeting abstracts (2004 and 2005) to identify English-language studies in humans. We included prospective clinical trials (phases I to III), case reports, and retrospective case series that reported tumor response, survival, quality of life, symptoms, and adverse effects. We excluded narrative reviews and studies that described only predictors of response, pharmacokinetics, or nonhuman results. For eligible studies, 1 reviewer abstracted data into evidence tables and a second reviewer verified the completed tables. For each agent and cancer combination, we created a summary table that listed the number of articles identified by study design and key outcomes. We scored identified studies by design (for example, phase I to III), size, and outcomes reported (for example, tumor response, survival, quality of life, or adverse effects). Our intention was not to expose the compendiawhich perform a vital function in oncologybut rather to examine their methods and the resulting comprehensiveness of their contents. We therefore did not score the evidence included in the compendia according to classic quality criteria. Instead, we adopted a conservative approach to content evaluation that entailed a simple count of independent studies, presentations of data, and other metrics but did not include evaluation of the quality and validity of the studies themselves. We used study design as a proxy for quality and validity, with phase III studies considered generally more valid than phase I or II studies. Update of 1 Agent and Cancer Combination In 2008, we repeated the systematic review for a single agent and cancer combination (gemcitabine for bladder cancer) by using the same methods, except we sought 2006 and 2007 conference abstracts. We chose the gemcitabine for bladder cancer indication because gemcitabine has been FDA-approved for longer than the other reviewed agents; gemcitabine has been widely studied (with the largest number of citations in our 2006 review); and, of the 3 gemcitabine combinations included, gemcitabine for bladder cancer had the fastest-evolving evidence base. This combination thus afforded compendia the most opportunity to demonstrate improvement. Analysis of Compendium Content Against Evaluation Criteria In 2006, we abstracted data for each of the 14 agent and cancer combinations from each of the 6 compendia. We evaluated all available versions (print and electronic) of the 6 compendia in 2006 but recorded data from the most current and complete version; in all cases, this was an electronic version. Data included whether the indication was explicitly stated; how the indication was graded; and comments on further refinement regarding the stage of cancer, treatment timing, route of administration, and use of monotherapy or combination therapy. We recorded outcomes mentioned specifically for the off-label use; toxicity data; presence of citations to evidence specifically regarding the off-label indication; number, identity, and years of citations; and time since any updates to the monograph or entry. We stratified publications cited in the compendia by study design, noting abstracts separately, and tabulated whether each compendium cited each publication; we compared the results with those of our systematic review. We updated this process in 2008 for the gemcitabine for bladder cancer indication. Role of the Funding Source The CMS funded the initial 2006 report through the Agency for Healthcare Research and Qualitys Evidence-Based Practice Center program. These agencies participated in formulating questions, reviewing the list of agent and cancer combinations, and commenting on report findings. The 2008 update of the report was unfunded. The agencies had no role in the writing or approval of the manuscript. Results Comparison of Stated Methods Used by Compendia All compendia described their scope and editorial policies, which did not change between the 2006 and 2008 reviews (Appendix Table 1). Because United States Pharmacopeia Drug Information for the Health Professional was discontinued in 2007, our results do not include that compendium even though it was part of the 2006 review. Here, we focus our evaluation on frequency of updates, use of available evidence, and transparency of decision-making processes. Appendix Table 1. Stated Methods of Selected Compendia Compendia had different update cycles for electronic versions, which varied from daily to quarterly (Table 1). Several compendia published multiple electronic editions; these differed in content and update schedules. Compendia did not always provide revision dates for drug m

Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis

BACKGROUND Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake. OBJECTIVE The authors examine the effects of dietary cholesterol on CVD risk in healthy adults by using systematic review and meta-analysis. DESIGN MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau Abstracts databases were searched through December 2013 for prospective studies that quantified dietary cholesterol. Investigators independently screened citations and verified extracted data on study and participant characteristics, outcomes, and quality. Random-effect models meta-analysis was used when at least 3 studies reported the same CVD outcome. RESULTS Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50). Dietary cholesterol statistically significantly increased both serum total cholesterol (17 trials; net change: 11.2 mg/dL; 95% CI: 6.4, 15.9) and low-density lipoprotein (LDL) cholesterol (14 trials; net change: 6.7 mg/dL; 95% CI: 1.7, 11.7 mg/dL). Increases in LDL cholesterol were no longer statistically significant when intervention doses exceeded 900 mg/d. Dietary cholesterol also statistically significantly increased serum high-density lipoprotein cholesterol (13 trials; net change: 3.2 mg/dL; 95% CI: 0.9, 9.7 mg/dL) and the LDL to high-density lipoprotein ratio (5 trials; net change: 0.2; 95% CI: 0.0, 0.3). Dietary cholesterol did not statistically significantly change serum triglycerides or very-low-density lipoprotein concentrations. CONCLUSION Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk.

Management Strategies for Asymptomatic Carotid Stenosis: A Systematic Review and Meta-analysis

BACKGROUND Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke. PURPOSE To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012. STUDY SELECTION Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed. DATA EXTRACTION Two investigators extracted information on study and population characteristics, results, and risk of bias. DATA SYNTHESIS Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year. LIMITATIONS Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy. CONCLUSION Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Development quality criteria to evaluate nontherapeutic studies of incidence, prevalence, or risk factors of chronic diseases: Pilot study of new checklists

OBJECTIVE To develop two checklists for the quality of observational studies of incidence or risk factors of diseases. STUDY DESIGN AND SETTING Initial development of the checklists was based on a systematic literature review. The checklists were refined after pilot trials of validity and reliability were conducted by seven experts, who tested the checklists on 10 articles. RESULTS The checklist for studies of incidence or prevalence of chronic disease had six criteria for external validity and five for internal validity. The checklist for risk factor studies had six criteria for external validity, 13 criteria for internal validity, and two aspects of causality. A Microsoft Access database produced automated standardized reports about external and internal validities. Pilot testing demonstrated face and content validities and discrimination of reporting vs. methodological qualities. Interrater agreement was poor. The experts suggested future reliability testing of the checklists in systematic reviews with preplanned protocols, a priori consensus about research-specific quality criteria, and training of the reviewers. CONCLUSION We propose transparent and standardized quality assessment criteria of observational studies using the developed checklists. Future testing of the checklists in systematic reviews is necessary to develop reliable tools that can be used with confidence.

Cochlear Implantation in Adults: A Systematic Review and Meta-analysis

IMPORTANCE Sensorineural hearing loss is the third leading cause of years lived with disability worldwide. Cochlear implants may provide a viable alternative to hearing aids for this type of hearing loss. The Coverage and Analysis Group at the Centers for Medicare & Medicaid Services was interested in an evaluation of recently published literature on this topic. In addition, this meta-analysis is to our knowledge the first to evaluate quality-of-life (QOL) outcomes in adults with cochlear implants. OBJECTIVE To evaluate the communication-related outcomes and health-related QOL outcomes after unilateral or bilateral cochlear implantation in adults with sensorineural hearing loss. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, Scopus, and previous reports from January 1, 2004, through May 31, 2012. STUDY SELECTION Published studies of adult patients undergoing unilateral or bilateral procedures with multichannel cochlear implants and assessments using open-set sentence tests, multisyllable word tests, or QOL measures. DATA EXTRACTION Five researchers extracted information on population characteristics, outcomes of interest, and study design and assessed the studies for risk of bias. Discrepancies were resolved by consensus. RESULTS A total of 42 studies met the inclusion criteria. Most unilateral implant studies showed a statistically significant improvement in mean speech scores as measured by open-set sentence or multisyllable word tests; meta-analysis revealed a significant improvement in QOL after unilateral implantation. Results from studies assessing bilateral implantation showed improvement in communication-related outcomes compared with unilateral implantation and additional improvements in sound localization compared with unilateral device use or implantation only. Based on a few studies, the QOL outcomes varied across tests after bilateral implantation. CONCLUSIONS AND RELEVANCE Unilateral cochlear implants provide improved hearing and significantly improve QOL, and improvements in sound localization are noted for bilateral implantation. Future studies of longer duration, higher-quality reporting, and large databases or registries of patients with long-term follow-up data are needed to yield stronger evidence.

Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis

BackgroundIncreasing rates of resistant and multidrug-resistant (MDR) P. aeruginosa in hospitalized patients constitute a major public health threat. We present a systematic review of the clinical and economic impact of this resistant pathogen.MethodsStudies indexed in MEDLINE and Cochrane databases between January 2000-February 2013, and reported all-cause mortality, length of stay, hospital costs, readmission, or recurrence in at least 20 hospitalized patients with laboratory confirmed resistant P. aeruginosa infection were included. We accepted individual study definitions of MDR, and assessed study methodological quality.ResultsThe most common definition of MDR was resistance to more than one agent in three or more categories of antibiotics. Twenty-three studies (7,881 patients with susceptible P. aeruginosa, 1,653 with resistant P. aeruginosa, 559 with MDR P. aeruginosa, 387 non-infected patients without P. aeruginosa) were analyzed. A random effects model meta-analysis was feasible for the endpoint of all-cause in-hospital mortality. All-cause mortality was 34% (95% confidence interval (CI) 27% – 41%) in patients with any resistant P. aeruginosa compared to 22% (95% CI 14% – 29%) with susceptible P. aeruginosa. The meta-analysis demonstrated a > 2-fold increased risk of mortality with MDR P. aeruginosa (relative risk (RR) 2.34, 95% CI 1.53 – 3.57) and a 24% increased risk with resistant P. aeruginosa (RR 1.24, 95% CI 1.11 – 1.38), compared to susceptible P. aeruginosa. An adjusted meta-analysis of data from seven studies demonstrated a statistically non-significant increased risk of mortality in patients with any resistant P. aeruginosa (adjusted RR 1.24, 95% CI 0.98 – 1.57). All three studies that reported infection-related mortality found a statistically significantly increased risk in patients with MDR P. aeruginosa compared to those with susceptible P. aeruginosa. Across studies, hospital length of stay (LOS) was higher in patients with resistant and MDR P. aeruginosa infections, compared to susceptible P. aeruginosa and control patients. Limitations included heterogeneity in MDR definition, restriction to nosocomial infections, and potential confounding in analyses.ConclusionsHospitalized patients with resistant and MDR P. aeruginosa infections appear to have increased all-cause mortality and LOS. The negative clinical and economic impact of these pathogens warrants in-depth evaluation of optimal infection prevention and stewardship strategies.