Amy Earley

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.

Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review.

Background: Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material. Purpose: To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians. Data Sources: A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011. Study Selection: Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material. Data Extraction: Reviewers extracted data on study population characteristics, measured GFR, creatinine assay, and equation performance. Data Synthesis: Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately >60 mL/min per 1.73 m 2 ) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient. Limitation: Methods of GFR measurement and study populations were heterogeneous. Conclusion: Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation. Primary Funding Source: Kidney Disease: Improving Global Outcomes.

Systematic Review: Blood Pressure Target in Chronic Kidney Disease and Proteinuria as an Effect Modifier

BACKGROUND The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear. PURPOSE To summarize trials comparing lower versus higher blood pressure targets in adult patients with CKD and focus on proteinuria as an effect modifier. DATA SOURCES MEDLINE and the Cochrane Central Register of Controlled Trials (July 2001 through January 2011) were searched for reports from randomized, controlled trials with no language restriction. STUDY SELECTION Authors screened abstracts to identify reports from trials comparing blood pressure targets in adults with CKD that had more than 50 participants per group; at least 1-year follow-up; and outcomes of death, kidney failure, cardiovascular events, change in kidney function, number of antihypertensive agents, and adverse events. DATA EXTRACTION Reviewers extracted data on study design, methods, sample characteristics, interventions, comparators, outcomes, number of medications, and adverse events and rated study quality and quality of analyses for proteinuria subgroups. DATA SYNTHESIS Three trials with a total of 2272 participants were included. Overall, trials did not show that a blood pressure target of less than 125/75 to 130/80 mm Hg is more beneficial than a target of less than 140/90 mm Hg. Lower-quality evidence suggests that a low target may be beneficial in subgroups with proteinuria greater than 300 to 1000 mg/d. Participants in the low target groups needed more antihypertensive medications and had a slightly higher rate of adverse events. LIMITATIONS No study included patients with diabetes. Trial duration may have been too short to detect differences in clinically important outcomes, such as death and kidney failure. Ascertainment and reporting of adverse events was not uniform. CONCLUSION Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. Whether a lower target benefits patients with proteinuria greater than 300 to 1000 mg/d requires further study.

Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND Lipid-lowering therapy is not widely used in persons with chronic kidney disease (CKD) despite a high burden of dyslipidemia and cardiovascular disease in this population. PURPOSE To synthesize evidence examining the effect of lipid-lowering therapy on clinical outcomes in persons with CKD. DATA SOURCES MEDLINE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from January 2000 through November 2011. STUDY SELECTION Randomized, controlled trials (RCTs) comparing lipid-lowering therapy with control treatment in persons with CKD, including subgroup analyses of trials in the general population. DATA EXTRACTION Abstracts were screened and data were extracted on study methodology, population, interventions, cardiovascular and kidney outcomes, and adverse events. Data were extracted by one author and confirmed by another. Study quality was determined by consensus. Random-effects model meta-analyses were performed. DATA SYNTHESIS 18 RCTs, all in adults, met the eligibility criteria. Five RCTs involved CKD populations, and 13 were CKD subgroup analyses from trials in the general population. Sixteen RCTs examined statins, and 2 examined statins plus ezetimibe. Lipid-lowering therapy does not improve kidney outcomes but decreases the risk for cardiac mortality (pooled risk ratio [RR] from 6 trials, 0.82 [95% CI, 0.74 to 0.91]; P< 0.001), cardiovascular events (including revascularization) (pooled RR from 9 trials, 0.78 [CI, 0.71 to 0.86]; P< 0.001), and myocardial infarction (pooled RR from 9 trials, 0.74 [CI, 0.67 to 0.81]; P< 0.001). Significant benefit was also seen for all-cause mortality but was limited by a high degree of heterogeneity. No benefit was found for other cardiovascular outcomes. Rates of adverse events were similar between intervention and comparator groups. LIMITATIONS Lack of data in children, heterogeneity among reviewed studies, and the possibility of selective reporting of outcomes and adverse events. CONCLUSION Lipid-lowering therapy decreases cardiac death and atherosclerosis-mediated cardiovascular events in persons with CKD.

Loss to Analysis in Randomized Controlled Trials in CKD

BACKGROUND Nephrology has a limited number of randomized controlled trials (RCTs). The quality of randomized trials is compromised further when not all participants randomly assigned are accounted for transparently. OBJECTIVES Systematically evaluate RCTs in individuals with chronic kidney disease regarding reporting and accounting of data missing in outcome analysis. STUDY DESIGN De novo empirical evaluation. SETTING & POPULATION English-language parallel-group design RCTs in adults with chronic kidney disease on dialysis therapy or with a kidney transplant published in MEDLINE in 2007 and 2008. OUTCOMES & MEASUREMENTS (1) How often was there loss to analysis, defined as not all randomly assigned participants included in primary outcome analysis? (2) How often was intention-to-treat analysis complete; in other words, included all randomly assigned participants in their originally allocated group? (3) How often were methods of data imputation reported? RESULTS Of 196 eligible RCTs, 27% did not clearly describe a primary outcome, 5% did not provide numbers of patients randomly assigned and analyzed, and 12% used time-to-event analysis. Of the remaining 110 studies, 58% had some loss to analysis, with a median loss to analysis of 10%. Fifty-four percent of trials claimed to have performed an intention-to-treat analysis, but only 44% of those included all participants randomly assigned. Only 5 of 110 (5%) studies mentioned imputation of missing data. LIMITATIONS Evaluation is restricted to analysis of primary study outcome. Only English-language publications were included. Exclusion of time-to-event analyses. CONCLUSIONS In variance to the reporting standards of CONSORT (Consolidated Standards of Reporting Trials), we found primary outcome designation missing in one-fourth of trials and poor quality in reporting and accounting of primary outcome data lost to analysis. Greater attention to transparency in handling and reporting loss to analysis will enhance the quality of trials in individuals with chronic kidney disease.

Long-Term Health Outcomes in Women With Silicone Gel Breast Implants: A Systematic Review

For decades, there has been some concern that silicone gel breast implants may be associated with a variety of diseases. Originally, some animal studies implicated silicone gel or oil in responses ranging from inflammation to increased antibodies related to connective tissue diseases (CTDs) (13). Although some studies of nonbreast prosthetic implants and breast augmentation by injection of foreign substances suggested a link with immune-modulated diseases (36), early studies of silicone implantation in humans did not demonstrate increased risk for cancer (79). In view of public concern and a determination that manufacturers had not provided sufficient data to demonstrate safety, in 1992 the U.S. Food and Drug Administration (FDA) requested a temporary moratorium on silicone gel breast implants, except in approved clinical studies (10). Silicone gel implants were reintroduced to the U.S. market in 2006 after FDA approval, which came with several conditions for manufacturers, including conducting extensive follow-up studies, continued analysis of explanted devices, and more detailed product labeling (11). Prior reports and evidence reviewsincluding a 1998 National Science Panel report (12), a 1999 Institute of Medicine report (4), and a 2011 FDA review (13)concluded that there was no evidence that silicone gel breast implants cause systemic health effects, such as cancer or autoimmune disease, but important limitations to the evidence existed. In 2012, the FDA and the American Society of Plastic Surgeons (ASPS) amended their existing Cooperative Research and Development Agreement to explore the development of a national breast implant registry for postmarket surveillance of all breast implants (14). No such large registry currently exists. This systematic review was commissioned to support development of the registry and to account for new analyses of large U.S. studies and recent reports from manufacturers to the FDA and Health Canada. Its objective is to summarize the state of the evidence on long-term health outcomes in women with (vs. without) silicone gel breast implants. Specifically, we are interested in 1) cancer; 2) connective tissue, rheumatologic, and autoimmune diseases; 3) neurologic diseases; 4) reproductive issues, including lactation; 5) offspring issues; and 6) mental health issues (depression and suicide). Methods An Advisory Panelcomprising representatives from the ASPS, the Plastic Surgery Foundation (PSF), industry, and the FDA, including a womens health research advocate and plastic surgeonswas convened to refine an initial list of key questions and outcomes drafted by the PSF. The panel provided input on the protocol and commented on the report to the PSF and this manuscript, but did not participate in the conduct of the systematic review. Study Selection Comprehensive literature searches were done in MEDLINE, EMBASE, and Ovid Healthstar (inception through 30 June 2015), as well as the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews (through the first quarter of 2015). Additional citations were solicited from the Advisory Panel. The searches combined terms for silicone gel implants and outcomes of interest (Table 1 of the Supplement). Four researchers screened citations in duplicate, and discrepancies were resolved in a group conference. Reference lists of existing systematic reviews, selected narrative reviews, and included studies were screened. Retrieved full-text articles were rescreened in duplicate. Supplement. Supplementary Material We included studies of any longitudinal design comparing women with and those without breast implants. Studies included women with any history of silicone gelfilled breast implants, excluding injected silicone, silicone tissue expanders, and recalled implants produced by Poly Implant Prothse (La Seyne-sur-Mer, France). At least one half the participants had to have silicone gel (vs. saline) implants, but to avoid inadvertently excluding eligible studies, we included studies that did not report the proportion of participants with silicone gel implants. Comparison groups included either women with no implants (including the general population), women with saline breast implants, or women undergoing other cosmetic surgery procedures. We excluded studies of only women with specific signs or symptoms (for example, joint pain) or only women seen in a specialty clinic (for example, evaluated by a rheumatologist), who do not represent the general population. The outcomes that we report on are 1) cancer; 2) CTDs and rheumatologic and autoimmune diseases; 3) neurologic diseases; 4) reproductive issues, including lactation; 5) offspring issues; and 6) mental health issues (depression and suicide). For breast cancer, we restricted analysis to primary cancer occurring in women with breast augmentation. The report to the PSF also includes CTDs and neurologic symptoms and single-group (noncomparative) studies that provide incidence rates (www.brown.edu/academics/public-health/research/evidence-based-medicine/research-initiatives/technical-reports). Study Extraction and Assessment Data from each study were extracted by 1 of 4 methodologists and confirmed by at least 1 other experienced methodologist. Extracted data included study, participant, and implant characteristics, including use for reconstruction or augmentation; study country; implantation dates and duration; outcomes (Table 2 of the Supplement); analytic methods; and results. We preferentially extracted the most adjusted models comparing implants with no implants, and we captured all factors that were adjusted for. We extracted both direct comparisons of implants versus no implants and indirect comparisons, such as standardized incidence ratios (SIRs). To assess study quality, we applied an adaptation of the McMaster Quality Assessment Scale of Harms (McHarm) Tool (15). We also applied selected quality questions from the Newcastle-Ottawa Scale for quality assessment of observational and casecontrol studies (16). The quality questions are listed in Tables 3 and 4 of the Supplement. Data Synthesis When necessary, we calculated unadjusted odds ratios (ORs). For each outcome, we conducted meta-analyses of effect size (ES) measures (i.e., OR, risk ratio [RR], hazard ratio) or SIRs if at least 3 studies (or independent cohorts) provided sufficient data to calculate the ES and its variance. We treated all ES measures as being equivalent and conducted random-effects model meta-analyses with the empirical Bayes method to estimate 2 values (17); if this method failed to converge on a 2 value, the residual maximum likelihood method was used. We conducted separate meta-analyses of direct within-study comparisons with a control group and of SIRs (with a general population control group). We also conducted subgroup meta-analyses for studies of only silicone gel implants. When studies reported data at multiple time points, data from the longest follow-up period were used. To explain statistical heterogeneity, by meta-regression we evaluated whether outcomes were ascertained by registry or physical examination (vs. self-reported by questionnaire) and whether implants were for augmentation or reconstruction (if at least 6 cohorts reported sufficient data to be included in meta-regression). All analyses were performed by using the metareg function in Stata, version 13 (StataCorp.). We categorized analyses on the basis of their modeling adjustment as unadjusted or as having adequate, inadequate, or unclear adjustment. Adequate adjustments accounted for likely confounders (e.g., family history, hormone use, weight, depression, and alcohol or tobacco use). Inadequate adjustments accounted for at most age, race, time since implantation, and calendar year. Role of the Funding Source The review was done under contract with the PSF. The PSF coordinated discussions with the Advisory Panel and review of the full report and the manuscript. The research team independently conducted the review and retained final determination of the review method, content, conclusions, and decision to publish. Results The literature search yielded 5171 citations (Appendix Figure). An additional 11 publications were added by the Advisory Panel, and 18 were identified from existing systematic reviews. On the basis of abstracts and titles, 207 articles were provisionally accepted for review. After the full text was screened, 32 studies (in 58 publications [7, 9, 1873]) met eligibility criteria. Nineteen studies were conducted in North America, 10 in northern Europe, 2 in southern Europe, and 1 in Australia. The implantations were performed from 1964 to 2003, and follow-up ranged from 1 to 27 years. Appendix Figure. Summary of evidence search and selection. Of 32 studies, 14 included augmentation only, 5 reconstruction only, and 6 both indications; 7 did not report reasons for implantation. Eleven studies reported data for only women with silicone gel implants (100% silicone gel), 13 reported that between 50% and more than 90% of women had silicone gel implants (vs. saline or other implants), and 8 did not report the proportion of women with silicone gel implants. The duration of implantation (i.e., follow-up duration) ranged from about 4 to 25 years. Only 9 studies provided baseline information on smoking and comorbid conditions among included participants. Summary tables for each outcome are included in Tables 5 to 32 of the Supplement. The most common risk of bias among studies was that analyses were mostly inadequately adjusted (4 studies) or not adjusted (27 studies) for potential confounders; several studies reported adjusted analyses for some outcomes, but unadjusted analyses for other outcomes. Only 4 studies reported adequately adjusted analyses, but the specific factors adjusted for were not consistently reported in 2 of these. Three studies were casecontrol studies; 29 were cohort studies. In 15 of 29

Effectiveness of Implantable Cardioverter Defibrillators for Primary Prevention of Sudden Cardiac Death in Subgroups: A Systematic Review

The implantable cardioverter defibrillator (ICD) is a battery-powered implantable device that can detect and terminate potentially life-threatening tachyarrhythmias via defibrillation to prevent SCD. Trials and systematic reviews have shown the efficacy of ICDs for primary prevention of sudden cardiac death (1). According to current guidelines, indications for ICD therapy for primary prevention of SCD include patients with left ventricular ejection fractions (LVEFs) of 35% or less due to previous myocardial infarction (MI) who are at least 40 days post-MI and are in NYHA (New York Heart Association) class II or III; patients with nonischemic dilated cardiomyopathy with LVEFs of 35% or less and who are in NYHA class II or III; or patients with left ventricular dysfunction due to previous MI who are at least 40 days post-MI, have an LVEF of 30% or less, and are in NYHA class I (24). Implantable cardioverter defibrillators were initially designed with the sole purpose of providing an electric shock to terminate a lethal ventricular rhythm. Currently, ICD therapy can electively be combined with cardiac resynchronization therapy (CRT) as cardiac resynchronization therapy with a defibrillator (CRT-D), the goal of which is not only improving survival but also functional status and symptoms of heart failure. Therefore, many patients may be eligible for ICD therapy. However, it is unclear whether the ICD benefit applies to the same degree to clinically important subgroups. As the competing risk for death increases with age, it has been proposed that the overall mortality benefit from prevention of SCD will diminish with age (5). Women have also been identified as a group that may not benefit from ICDs to the same extent as men (6, 7). Other subgroups have been considered on the basis of potential effect modifiers, including LVEF, time since revascularization, and comorbid conditions, such as diabetes and kidney disease (818). This review examines the effectiveness of ICD treatment versus no ICD treatment for primary prevention of SCD across important clinical subgroups in comparative studies. Methods This review is based on a Health Technology Assessment prepared by the Tufts Evidence-based Practice Center under contract with the Agency for Healthcare Research and Quality. The full text of the report is available at www.effectivehealthcare.ahrq.gov(1). Data Sources We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through 3 September 2013 with no language restrictions. Table 1 of the Supplement shows the search strategy. Supplement. Tables and Figures Study Selection We included randomized, controlled trials and longitudinal, nonrandomized, comparative studies with at least 10 participants per group. For nonrandomized studies, only those that used concurrent controls and reported a multivariable analysis were eligible. The population of interest was adults eligible to receive an ICD for primary prevention of SCD. Participants had to be followed from the time of ICD implantation, not from an arbitrary time after ICD implantation. We examined effect modification in reported subgroups for different patient and clinical characteristics (including age, sex, race or ethnicity, NYHA class, LVEF, heart failure, left bundle branch block [LBBB], QRS interval, heart disease, time since MI, previous coronary revascularization, time since coronary revascularization, diabetes, blood urea nitrogen level, and kidney disease). The comparison of interest was ICD with or without CRT versus no ICD. We did not implement a minimum follow-up duration. Outcomes of interest were all-cause mortality and death due to SCD. Data Extraction and Quality Assessment We screened titles and abstracts using Abstrackr (Brown University, Providence, Rhode Island) (19). Seven researchers double-screened the abstracts after iterative training of all reviewers on the same batches of abstracts. Discordant decisions and queries were resolved at group meetings. Full-text articles were retrieved for all potentially relevant abstracts and rescreened by the same researchers. Each study was extracted by 1 experienced methodologist, and results and quality were reviewed and confirmed by 1 other methodologist. Data extraction included elements for population characteristics, sample size, study design, descriptions of the ICD and comparison interventions, outcomes, subgroup factors (demographic and clinical features at baseline), and relevant results analyses. When necessary, we estimated figure data using Engauge Digitizer, version 2.14 (SourceForge, Mountain View, California). We assessed the quality of the subgroup analyses on the basis of recently proposed criteria for reporting and interpreting subgroup analyses (Table 1) (20, 21). We examined published articles and related study design papers but did not contact investigators for unpublished data. Table 1. Quality Assessment of Subgroup Analyses in Studies of ICD vs. No ICD Data Synthesis and Analysis For outcomes with subgroup data from at least 4 randomized, controlled trials with sufficiently similar comparisons of interest and adequate data, we conducted profile likelihood random-effects model meta-analyses because of the relatively small number of studies (22). If the profile likelihood model did not converge, we did a fixed-effect model meta-analysis. For each subgroup analysis, we calculated a relative odds ratio (ROR), dividing the odds ratio (OR) or similar measure of death for 1 subgroup by the other. We preferentially used adjusted ORs (or hazard ratios). When necessary, we calculated ORs on the basis of reported counts. Meta-analyses were done on the RORs. The SEs of the natural logarithms of the ORs (or hazard ratios) for each subgroup were combined assuming no correlation between independent subgroups, such that where A and B are the 2 subgroups. Statistical heterogeneity was assessed with the I 2 statistic and the chi-square P value. Meta-analyses were conducted with the metaan package in Stata, version 11.2 (StataCorp, College Station, Texas). We extracted and tabulated the reported P values of the difference in effect between the subgroups of interest. Role of the Funding Source The Agency for Healthcare Research and Quality participated in formulating the study questions and developing the protocol but did not participate in the literature search, determination of study eligibility criteria, data analysis or interpretation, preparation or review of the manuscript, or the decision to submit the manuscript for publication. Results Figure 1 of the Supplement summarizes the search yield. Of 11314 abstracts, 27 articles described 10 randomized and 4 nonrandomized comparative studies of ICD versus no ICD treatment (Table 2 of the Supplement). Of these, 10 studies (in 19 articles) provided data to our subgroup analyses (812, 1418, 2331). Six of these studies were conducted in the United States and Canada, 1 in Germany, and 3 in both the United States and Europe. Nine studies examined the comparison of ICD only versus no ICD. A single U.S. study, however, compared CRT-D versus no ICD, which we treated as a comparison of ICD versus no ICD for the purpose of this review. With regard to age and sex, the study by Hernandez and colleagues (12), which focused exclusively on Medicare patients, was an outlier: Mean age was 74.7 years, and 40% of patients were women. Across the other studies, mean age was 63 years (95% CI, 61 to 65), and 25% (CI, 21% to 28%) were women. Subgroup data from at least 2 studies with sufficiently similar comparisons of subgroups are shown in Table 2. Table 3 of the Supplement shows all subgroup comparisons, including those that were examined only once. Table 2. Subgroup Analyses Data and Meta-analysis of ICD vs. No ICD for All-Cause Death* All-Cause Mortality All 10 randomized (810, 1418, 2426, 2938) and 4 nonrandomized studies (11, 12, 39, 40) provided consistent and precise findings of a statistically significant benefit of ICD to reduce all-cause mortality rates (Figure 2 of the Supplement) (1). Use of ICD for patients who had no recent MI (within 30 days) and no concurrent coronary revascularization reduced the risk for all-cause mortality by approximately 31% (CI, 21% to 40%) over the course of 3 to 7 years after implantation. Additional details about the overall meta-analysis can be found in the full Health Technology Assessment (1). The 10 studies that conducted subgroup analyses did not support a statistical difference in the benefit of ICD for all-cause mortality across subgroups on the basis of age, sex, race or ethnicity, NYHA class, LVEF, heart failure, LBBB, QRS interval, heart disease, time since MI, previous coronary revascularization, time since coronary revascularization, diabetes, blood urea nitrogen level, and kidney disease. The single exception was 1 study that found that ICD placement was statistically significantly more effective in patients in NYHA class II versus NYHA class III (8) (Table 2). Meta-analyses of the ROR of death for subgroups on the basis of sex (Figure 1), age (<65 years vs. 65 years) (Figure 2), and QRS interval (<120 msec vs. 120 msec) (Table 2) found no statistically significant differences and were statistically homogeneous. Other comparisons of subgroups were not meta-analyzed because too few studies compared them; however, no consistent differences between subgroups were found across studies (Table 2). Figure 1. Men vs. women: RORs of implantable cardioverter defibrillators vs. no implantable cardioverter defibrillators for all-cause mortality. P het = P value for the heterogeneity across studies; ROR = relative odds ratio. * ROR, relative risk ratio, or relative hazard ratio, as reported by studies. Odds ratio, risk ratio, or hazard ratio, as reported by studies. Figure 2. Younger vs. older subgroups: RORs of implantable cardioverter defibrillators vs. no implantable cardioverter defibrillators fo

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications–a cross-sectional study

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. Results In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Conclusions Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Fluorescence in situ hybridization testing for the diagnosis of high-grade cervical abnormalities: a systematic review.

Objective We examined the diagnostic performance of fluorescence in situ hybridization (FISH) tests on cervical cytology for precancerous lesions or cancer on cervical histology. Materials and Methods A search was conducted in MEDLINE, the Cochrane Central Register of Controlled Trials, and Scopus through September 3, 2013. Eleven studies examined FISH tests for telomerase RNA component gene (TERC), myelocytomatosis oncogene (MYC), or human papillomavirus (HPV) type 16 or 18 in samples exhibiting atypical squamous cells of unknown significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). None examined HPV-positive, cytologically normal samples. We extracted data on the sensitivity and specificity for high-grade cervical intraepithelial neoplasia (CIN 2+ or CIN 3+). Results Fluorescence in situ hybridization test probes and thresholds varied across studies. Included populations were convenience samples. Only 1 study testing for TERC specified HPV status. In meta-analysis, FISH for TERC in LSIL (9 studies, 1,082 cases) had a summary sensitivity of 0.76 (95% confidence interval = 0.63–0.85) and a summary specificity of 0.78 (95% confidence interval = 0.57–0.91) for CIN 2+. Fluorescence in situ hybridization for TERC in ASC-US (3 studies, 839 cases) showed sensitivities ranging from 0.75 to 1.00 and specificities from 0.87 to 0.93 for CIN 2+. For CIN 3+, sensitivity and specificity appeared similar, although a small number of studies preclude firm conclusions. For FISH tests for HPV, we found only few studies with small sample sizes. Conclusions The evidence on FISH testing is limited given the small number of studies for each cytology subgroup and the lack of studies in well-defined screening contexts stratifying participants by HPV status.

Практическое клиническое руководство KDIGO по ведению пациентов после трансплантации почки

Практическое клиническое руководство по наблюдению и лечению пациентов с пересаженной почкой предназначено для оказания помощи практикующим врачам, занимающимся лечением взрослых и детей, перенесших трансплантацию почки. Руководство разработано в соответствии с принципами доказательного метода, используемого в медицине, рекомендации по тактике ведения пациента основаны на систематических обзорах соответствующих клинических исследований. Критический анализ качества доказательств и степени убедительности рекомендаций проведен в соответствии с правилами GRADE (Grades of Recommendation Assessment, Development, and Evaluation – расчет, разработка и оценка уровней степени убедительности рекомендаций). Содержит рекомендации по иммуносупрессии, мониторингу состояния трансплантата, профилактике и лечению инфекций, сердечно-сосудистых заболеваний, новообразований и других осложнений, которые являются наиболее распространенными среди реципиентов трансплантированной почки, включая гематологические нарушения и поражение костной ткани. Ограниченность имеющихся доказательств, особенно в связи с отсутствием конкретных результатов клинических испытаний, является предметом обсуждения, в соответствии с ними приведены предложения для будущих исследований. Источник: American Journal of Transplantation. – 2009. – Vol. 9, (Suppl. 3). – P. 6–9.