Nancy Greer

The Magnitude of Acute Serum Creatinine Increase After Cardiac Surgery and the Risk of Chronic Kidney Disease, Progression of Kidney Disease, and Death

BACKGROUND Long-term outcomes after acute kidney injury remain poorly defined. We determined the association between the magnitude of creatinine increase after cardiac surgery and the risk of incident chronic kidney disease (CKD), CKD progression, and death. METHODS We identified 29,388 individuals who underwent cardiac surgery at Veterans Affairs hospitals between November 1999 and September 2005. The magnitude of creatinine increase was defined by the percent change from baseline to peak creatinine levels after cardiac surgery and categorized as none (≤0%) or as class I, (1%-24%), II (25%-49%), III (50%-99%), or IV (≥100%). Cox proportional hazard models were used to examine the association between the magnitude of creatinine increase and outcomes. RESULTS The relative hazards for outcomes increased monotonically with greater increases in creatinine levels compared with no change in creatinine levels. The relative hazards for adverse outcomes were significantly higher immediately after the creatinine increase and attenuated over time. Three months after surgery, creatinine increase classes I, II, III, and IV were associated with a greater risk of incident CKD (hazard ratios [HRs] 2.1, 4.0, 5.8, and 6.6, respectively; all P<.01), progression of CKD stage (HRs 2.5, 3.8, 4.4, and 8.0; all P<.01), and long-term mortality (HRs 1.4, 1.9, 2.8, and 5.0; all P<.01). At 5 years, the associations were lower in magnitude: incident CKD (HRs 1.4, 1.9, 2.3, and 2.3; all P<.01), CKD progression (HRs 1.5, 1.7, 1.7, and 2.4; all P<.01), and mortality (HRs 1.0, 1.2, 1.4, and 1.8; all P<.01, except class I). CONCLUSION The magnitude of creatinine increase after cardiac surgery is associated in a graded manner with an increased risk of incident CKD, CKD progression, and mortality.

KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update

The National Kidney Foundations Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.

Prevalence, assessment, and treatment of mild traumatic brain injury and posttraumatic stress disorder: a systematic review of the evidence.

Background:Iraq and Afghanistan war veterans are returning from combat having sustained traumatic brain injury, most commonly mild traumatic brain injury (mTBI), and experiencing posttraumatic stress disorder (PTSD). Clinical guidelines for mTBI and PTSD do not focus on the co-occurrence of these conditions (mTBI/PTSD). A synthesis of the evidence on prevalence, diagnostic accuracy, and treatment effectiveness for mTBI/PTSD would be of use to clinicians, researchers, and policymakers. Methods:We conducted a systematic review of studies identified through PubMed, PsycINFO, REHABDATA, Cochrane Library, pearling, and expert recommendations. Peer-reviewed English language studies published between 1980 and June, 2009 were included if they reported frequencies of traumatic brain injury and PTSD, or diagnostic accuracy or treatment effectiveness specific to mTBI/PTSD. Results:Thirty-four studies met inclusion criteria. None evaluated diagnostic accuracy or treatment effectiveness. Studies varied considerably in design. Frequency of mTBI/PTSD ranged from 0% to 89%. However, in 3 large studies evaluating Iraq and Afghanistan war veterans, frequencies of probable mTBI/PTSD were from 5% to 7%; among those with probable mTBI, frequencies of probable PTSD were from 33% to 39%. Discussion:The wide range of mTBI/PTSD frequency levels was likely due to variation across study parameters, including aims and assessment methods. Studies using consistent, validated methods to define and measure mTBI history and PTSD are needed.

Teledermatology for diagnosis and management of skin conditions: a systematic review.

OBJECTIVE We performed a systematic review of the literature addressing teledermatology: (1) diagnostic accuracy/concordance; (2) management accuracy/concordance; (3) clinical outcomes; and (4) costs. METHODS Peer-reviewed controlled trials published in English between 1990 and 2009 were identified through MEDLINE and PubMed searches. RESULTS Of 78 included studies, approximately two-thirds comparing teledermatology and clinic dermatology found better diagnostic accuracy with clinic dermatology. Diagnostic concordance of store and forward with clinic dermatology was good; concordance rates for live interactive and clinic dermatology were higher, but based on fewer patients. Overall rates of management accuracy were equivalent, but teledermatology and teledermatoscopy were inferior to clinic dermatology for malignant lesions. Management concordance was fair to excellent. There was insufficient evidence to evaluate clinical course outcomes. Patient satisfaction and preferences were comparable. Teledermatology reduced time to treatment and clinic visits and was cost-effective if certain assumptions were met. LIMITATIONS Heterogeneity in studies (design, skin conditions, outcomes) limited the ability to pool data. CONCLUSION The benefits of teledermatology need to be evaluated in the context of potential limitations.

Fecal Microbiota Transplantation for Clostridium difficile Infection: A Systematic Review

Key Summary Points Fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) is increasingly used, primarily for recurrent CDI but also for refractory CDI and treatment of the initial CDI episode. Although 35 studies of FMT for CDI were identified, only 2 were randomized, controlled trials (RCTs), with only 1 RCT having a non-FMT comparator group. Among the 36 patients who received FMT for recurrent CDI in the 2 RCTs, 27 (75%) had resolution of symptoms without recurrence. Among the 480 patients in 21 case-series studies who received FMT for recurrent CDI, 85% had resolution of symptoms without recurrence. Few studies reported on FMT for refractory CDI or for treatment of the initial CDI episode; among these, success rates were highly variable. Since its discovery as the cause of pseudomembranous colitis in 1978 (1, 2), Clostridium difficile has become an increasingly important pathogen. Initially largely confined to patients with health care exposure, C. difficile infection (CDI) now also affects persons with no or limited contact with the health care system (3). In 2013, the Centers for Disease Control and Prevention placed C. difficile into the top threat category (urgent) in its threat report on antimicrobial resistance (4). The high rate of recurrence15% to 30% of patients after their initial CDI episode and increasing thereafteris a major challenge (5, 6). Several treatment or recurrence episodes may result in repeated hospitalizations, clinic visits, deconditioning, malnourishment, and fecal incontinence. Antimicrobial treatment of recurrent disease yields success rates between 30% and 80%, depending on the number of recurrences and the agent and treatment duration selected (58). These suboptimal response rates have spurred investigation of additional treatment options, including fecal microbiota transplantation (FMT). Severe colonic microbiome (normal colonic bacteria) alterations are characteristic of CDI. Restoring the microbiome has been proposed to prevent recurrence, and probiotics are the most widely used intervention. However, probiotic microorganisms are less diverse than those of the organisms that characterize the colonic microbiome in healthy persons (9). Fecal microbiota transplantation is increasingly used as a treatment of recurrent CDI on the basis of the idea that importing the colonic microbiome of a healthy person is a simple method of reconstituting the normal colonic flora. Most FMT cases in the medical literature are from noncontrolled case-series studies (10). Reported success rates of up to 100% and the publication of a randomized, controlled trial (RCT) comparing FMT with antimicrobial treatment (11) have increased interest in FMT, even as regulations have evolved. The U.S. Food and Drug Administration currently requires an investigational new drug application for human studies of FMT but not for clinical use in treating CDI. The first reported use of FMT (delivered via enema) in medical literature was a small case-series study of hospitalized patients. Since then, various reports have described performing the procedure outside of the hospital, including at home by means of self-administered enema (12). Timing and frequency of FMT has also varied; most are administered in a single session, whereas others have relied on serial administration over several days. Several guidelines and reviews are available to help providers select appropriate patients for FMT, guide the selection and screening of stool donors, and choose from among the delivery methods (1315). The 2 most recent guidelines differ about the strength of evidence supporting FMTa European guideline stated that FMT is strongly recommended (A-I) after a second recurrence of CDI (13), whereas a guideline from the American College of Gastroenterology offered a more cautious recommendation, stating that if there is a third recurrence after a pulsed vancomycin regimen, fecal microbiota transplant (FMT) should be considered. (Conditional recommendation, moderate-quality evidence) (14). We did a systematic review of the evidence about the effectiveness of FMT for recurrent, refractory, and initial CDI and looked for evidence that effectiveness varied by method of transplantation. We also assessed harms of FMT and procedure acceptability. This report is derived from work done for a larger U.S. Department of Veterans Affairs Evidence-based Synthesis Program review. Methods Search Strategy We searched MEDLINE for articles published in English from 1980 to January 2015 that enrolled human participants and described FMT for known or suspected CDI (Appendix Table). We also searched the Cochrane Library and ClinialTrials.gov through January 2015. Our search included studies of any design, although we excluded case reports unless they reported harms. Additional articles, including some predating our search period or using nonstandard descriptors for CDI or FMT, were identified from hand-searching reference lists of existing systematic reviews and included studies as well as from suggestions by a technical expert panel. Appendix Table. Search Strategy Study Selection and Definitions Titles, abstracts, and articles were independently reviewed by 2 investigators, and disagreements were resolved by discussion and involvement of a third investigator, if needed. We considered initial CDI to be the first occurrence of CDI in a particular patient, recurrent CDI to be an episode occurring after previous treatment and favorable response for at least 1 previous episode, and refractory CDI to be an episode that did not respond to antimicrobial treatment. Data Abstraction and Quality Assessment Study characteristics, patient characteristics, and outcomes data were abstracted from included articles. Because all but 2 of the included studies were case-series studies, we did not formally assess quality but rather noted that conventional methods for rating strength of evidence would classify even well-conducted and reported case-series studies as high risk of bias (16). Therefore, strength of evidence would typically be considered insufficient or low. For the 2 RCTs, quality was assessed on the following criteria: allocation concealment, blinding, analysis approach, and description of withdrawalsa modification of the Cochrane approach to determining risk of bias (17). Our key outcomes included resolution of symptoms (primary outcome), time to resolution of symptoms, recurrence, all-cause mortality, and adverse events. We report results after a single administration of FMT or, in the case of studies that specified serial administration of FMT on successive days, a single prespecified series of administrations. In several studies, patients having recurrence were offered repeated FMT; these patients were categorized as having unsuccessful FMT because they met the recurrence outcome. Data Synthesis and Analysis Most findings are summarized narratively. Because the included studies report outcomes on small numbers of patients derived largely from case-series studies, any pooled estimate of the effect size and a surrounding CI was considered to be of questionable validity. Therefore, we report descriptive summaries of each included study and an overall percentage of patients remaining free of recurrent CDI. Role of the Funding Source This review was funded by the U.S. Department of Veterans Affairs. The funding source had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Members of a technical expert panel and peer reviewers of the evidence report provided advice and feedback. Technical expert panel members and peer reviewers were not compensated for their contributions. Results Our literature search yielded 190 abstracts or titles. We excluded 129 articles after abstract review and performed full-text reviews of 61 articles; of those, we excluded 51, leaving 10 articles. From hand-searching reference lists of systematic reviews and included studies and suggestions from technical expert panel members, we identified another 25 articles for a total of 35 included studies: 2 RCTs, 28 case-series studies, and 5 case reports (Figure). Figure. Summary of evidence search and selection. CDI = Clostridium difficile infection; FMT = fecal microbiota transplantation; RCT = randomized, controlled trial. * Included 1 RCT. FMT for Recurrent CDI Data From RCTs Two small RCTs with moderate risk of bias (11, 18) reported use of FMT for patients with recurrent CDI. The first compared FMT using a nasoduodenal tube with 2 control groups (43 patients; 1 withdrew after random assignment); 81% of FMT patients achieved resolution of symptoms within 3 months compared with 31% and 23% for the vancomycin and vancomycin-plus-bowel lavage control groups, respectively (P < 0.001 for FMT vs. both control groups) (11). The study, which we rated as moderate quality, was unblinded and done in the Netherlands. It was terminated after the investigators saw extremely low response rates in the control groups, which differed substantially from the 60% rate used for calculations of sample sizes. Patients had a mean age of 70 years, and 58% were men. Previous CDI episodes were numbered from 1 to 9. Administration of FMT was done after 4 to 5 days of oral vancomycin (500 mg 4 times daily), whereas the control groups received the same dose of vancomycin for 14 days. The second RCT compared 2 FMT treatment approaches, nasogastric tube and colonoscopy, in 20 patients. Overall, 70% of patients had resolution of symptoms; the difference between treatment approaches was not significant (60% in the nasogastric tube group and 80% in the colonoscopy group; P= 0.63) (18). This moderate-quality study was unblinded, did not include a non-FMT control group, and was done in the United States. The patients in this trial were

Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes.

BACKGROUND Anticoagulation with vitamin K antagonists reduces major thromboembolic complications in at-risk patients. With portable monitoring devices, patients can conduct their own international normalized ratio testing and dose adjustment at home. PURPOSE To determine whether patient self-testing (PST), alone or in combination with self-adjustment of doses (patient self-management [PSM]), is associated with a reduction in thromboembolic complications and all-cause mortality without an increase in major bleeding events compared with usual care. DATA SOURCES MEDLINE and the Cochrane Central Register of Controlled Trials. STUDY SELECTION Studies published in English from 1966 to October 2010 that enrolled outpatient adults receiving long-term (>3 months) oral anticoagulant therapy and that compared PST or PSM with care in a physicians office or an anticoagulation clinic were included. DATA EXTRACTION Two investigators reviewed each article. Three investigators extracted data from articles that met inclusion criteria by using standardized data abstraction forms. Studies were assessed for quality, and the overall strength of evidence was rated for each clinical outcome. DATA SYNTHESIS Twenty-two trials, with a total of 8413 patients, were included. In one half of the trials, fewer than 50% of potentially eligible persons successfully completed the training and agreed to be randomly assigned. Patients randomly assigned to PST or PSM had lower total mortality (Peto odds ratio [OR], 0.74 [95% CI, 0.63 to 0.87]), lower risk for major thromboembolism (Peto OR, 0.58 [CI, 0.45 to 0.75]), and no increased risk for a major bleeding event (Peto OR, 0.89 [CI, 0.75 to 1.05]). The strength of evidence was moderate for the bleeding and thromboembolism outcomes but low for mortality. Eight of 11 trials reported that patient satisfaction, quality of life, or both was better with PST or PSM than with usual care. LIMITATIONS In one half of the trials, fewer than 50% of the potentially eligible patients were randomly assigned. Only 5 trials were considered high quality, and only 2 were conducted in the United States. No studies addressed whether PST or PSM is safe during the high-risk initiation phase. CONCLUSION Compared with usual care, PST with or without PSM is associated with significantly fewer deaths and thromboembolic events, without increased risk for a serious bleeding event, for a highly selected group of motivated adult patients requiring long-term anticoagulation with vitamin K antagonists. Whether this care model is cost-effective and can be implemented successfully in typical U.S. health care settings requires further study. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service.

Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to 3: A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline

This analysis suggests that one-time general consent is better than a gift model for addressing 5 central challenges that arise in the context of obtaining and storing human biological samples for future research. This conclusion supports the suggestion made in a recent Advance Notice of Proposed Rulemaking to incorporate one-time general consent for research with human biological samples into any revisions of the federal regulations.Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes. This review summarizes evidence on the benefits and harms of screening ...

Advanced Wound Care Therapies for Nonhealing Diabetic, Venous, and Arterial Ulcers: A Systematic Review

BACKGROUND Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system. PURPOSE To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers. DATA SOURCES MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists. STUDY SELECTION English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies. DATA EXTRACTION Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator. DATA SYNTHESIS For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing. LIMITATIONS Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies. CONCLUSION Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited. PRIMARY FUNDING SOURCE Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.

Antimicrobial stewardship in outpatient settings: a systematic review.

OBJECTIVE Evaluate the effect of outpatient antimicrobial stewardship programs on prescribing, patient, microbial outcomes, and costs. DESIGN Systematic review METHODS Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (eg, infectious conditions, prescription services) evaluating stewardship programs in outpatient settings and reporting outcomes of interest. Data regarding study characteristics and outcomes were extracted and organized by intervention type. RESULTS We identified 50 studies eligible for inclusion, with most (29 of 50; 58%) reporting on respiratory tract infections, followed by multiple/unspecified infections (17 of 50; 34%). We found medium-strength evidence that stewardship programs incorporating communication skills training and laboratory testing are associated with reductions in antimicrobial use, and low-strength evidence that other stewardship interventions are associated with improved prescribing. Patient-centered outcomes, which were infrequently reported, were not adversely affected. Medication costs were generally lower with stewardship interventions, but overall program costs were rarely reported. No studies reported microbial outcomes, and data regarding outpatient settings other than primary care clinics are limited. CONCLUSIONS Low- to moderate-strength evidence suggests that antimicrobial stewardship programs in outpatient settings improve antimicrobial prescribing without adversely effecting patient outcomes. Effectiveness depends on program type. Most studies were not designed to measure patient or resistance outcomes. Data regarding sustainability and scalability of interventions are limited.

Antimicrobial Stewardship Programs in Inpatient Hospital Settings: A Systematic Review

OBJECTIVE Evaluate the evidence for effects of inpatient antimicrobial stewardship programs (ASPs) on patient, prescribing, and microbial outcomes. DESIGN Systematic review. METHODS Search of MEDLINE (2000 through November 2013), Cochrane Library, and reference lists of relevant studies. We included English language studies with patient populations relevant to the United States (ie, infectious conditions and prescriptions required for antimicrobials) that evaluated ASP interventions and reported outcomes of interest. Study characteristics and outcomes data were extracted and reviewed by investigators and trained research personnel. RESULTS Few intervention types (eg, audit and feedback, guideline implementation, and decision support) substantially impacted patient outcomes, including mortality, length of stay, readmission, or incidence of Clostridium difficile infection. However, most interventions were not powered adequately to demonstrate impacts on patient outcomes. Most interventions were associated with improved prescribing patterns as measured by decreased antimicrobial use or increased appropriate use. Where reported, ASPs were generally associated with improvements in microbial outcomes, including institutional resistance patterns or resistance in the study population. Few data were provided on harms, sustainability, or key intervention components. Studies were typically of short duration, low in methodological quality, and varied in study design, populations enrolled, hospital setting, ASP intent, intervention composition and implementation, comparison group, and outcomes assessed. CONCLUSIONS Numerous studies suggest that ASPs can improve prescribing and microbial outcomes. Strength of evidence was low, and most studies were not designed adequately to detect improvements in mortality or other patient outcomes, but obvious adverse effects on patient outcomes were not reported.