Anna Glechner

Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: A systematic review and meta-analysis

BACKGROUND The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. METHODS We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1 year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. RESULTS Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. CONCLUSION The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients.

Extended-release opioids in the management of cancer pain: a systematic review of efficacy and safety.

Despite the increased availability of strong analgesics and evidence‐based recommendations for pain management, under‐treatment of cancer‐related pain is still common. Extended‐release (ER) opioids, in contrast to immediate‐release opioids, provide prolonged analgesia. In this review, we aimed to compare the efficacy and safety of ER opioid analgesics in managing moderate‐to‐severe pain in patients with cancer. We identified randomized controlled trials (RCTs) and controlled observational studies that compared ER opioids in cancer pain by searching several databases, including MEDLINE, EMBASE and the Cochrane Library. Two independent reviewers screened and evaluated retrieved records to select relevant studies. We dually assessed the risk of bias for included studies and evaluated the overall strength of evidence for six critical outcomes using Grading of Recommendations Assessment, Development and Evaluation level of evidence. A total of three double‐blind RCTs (comparative efficacy and adverse events), two non‐blinded RCTs and four observational studies (comparative adverse events) were included in this review. All randomized trials and one observational study were of high risk of bias, and three observational studies of unclear risk of bias. The level of evidence for the selected efficacy and safety outcomes was low and very low. We synthesized the findings qualitatively because of the paucity of relevant studies as well as variable study design and quality. This systematic review indicates no substantial differences in efficacy and frequent adverse events among ER opioids for cancer pain. The body of evidence, however, is limited to few comparisons and fraught with methodological shortcomings.

Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review.

To systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).

The predictive validity of quality of evidence grades for the stability of effect estimates was low: a meta-epidemiological study

OBJECTIVE To determine the predictive validity of the U.S. Evidence-based Practice Center (EPC) approach to GRADE (Grading of Recommendations Assessment, Development and Evaluation). STUDY DESIGN AND SETTING Based on Cochrane reports with outcomes graded as high quality of evidence (QOE), we prepared 160 documents which represented different levels of QOE. Professional systematic reviewers dually graded the QOE. For each document, we determined whether estimates were concordant with high QOE estimates of the Cochrane reports. We compared the observed proportion of concordant estimates with the expected proportion from an international survey. To determine the predictive validity, we used the Hosmer-Lemeshow test to assess calibration and the C (concordance) index to assess discrimination. RESULTS The predictive validity of the EPC approach to GRADE was limited. Estimates graded as high QOE were less likely, estimates graded as low or insufficient QOE more likely to remain stable than expected. The EPC approach to GRADE could not reliably predict the likelihood that individual bodies of evidence remain stable as new evidence becomes available. C-indices ranged between 0.56 (95% CI, 0.47 to 0.66) and 0.58 (95% CI, 0.50 to 0.67) indicating a low discriminatory ability. CONCLUSION The limited predictive validity of the EPC approach to GRADE seems to reflect a mismatch between expected and observed changes in treatment effects as bodies of evidence advance from insufficient to high QOE.

Ezetimibe-Statin Combination Therapy: Efficacy and Safety as Compared With Statin Monotherapy — a Systematic Review

BACKGROUND To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. METHODS This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. RESULTS Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). CONCLUSION In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

A case study of pooled-studies publications indicated potential for both valuable information and bias

OBJECTIVES Pooled-studies publications (PSPs) present statistical analyses of multiple randomized controlled trials without a systematic literature search or critical appraisal. We explored the characteristics of PSPs and their potential impact on a systematic review (SR). STUDY DESIGN AND SETTING We systematically evaluated PSPs excluded from an SR of second-generation antidepressants. We analyzed their basic characteristics, risk of bias, and the effect of new data on review conclusions. RESULTS We identified 57 PSPs containing a median of five trials (range, 2-11) and 1,233 patients (range, 117-2,919). Ninety-six percent of PSPs were industry funded, and 49% of PSPs contained unpublished data. The median number of citations for PSPs was 29 (range, 0-549). Only 7% planned pooling a priori, and 19% combined trials with identical protocols. Fifty-nine percent of PSPs eligible for general efficacy provided no new data. For some subgroups and accompanying symptoms (e.g., anxiety, insomnia, melancholia, fatigue, sex, and race), more than 30% of PSPs presented entirely new data or data that could alter the strength of the evidence available in the SR. CONCLUSION In this case study, PSPs provided new information on subgroups and secondary outcomes; however, guidance for reviewers and development of a system to assess their susceptibility to bias are required.

Ezetimibe-Statin Combination Therapy: Efficacy and Safety as Compared With Statin Monotherapy

BACKGROUND To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. METHODS This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. RESULTS Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). CONCLUSION In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

Effects of lifestyle changes on adults with prediabetes: A systematic review and meta-analysis

AIMS To assess the efficacy, safety, and cost-effectiveness of lifestyle intervention, compared with treatment as usual in people with prediabetes as defined by the American Diabetes Association. For older studies, we used the 1985 World Health Organization definition. METHODS We systematically searched multiple electronic databases and referenced lists of pertinent review articles from January 1980 through November 2015. We performed an update search in MEDLINE on April 26, 2017. Based on a priori established eligibility criteria, we dually reviewed the literature, extracted data, and rated the risk of bias of included studies with validated checklists. To assess the efficacy of lifestyle intervention to prevent or delay further progression to type 2 diabetes, we conducted a random-effects meta-analysis. We assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULT Pooled results of 16 randomized controlled trials showed that people with prediabetes who received lifestyle intervention had a lower rate of progression to type 2 diabetes after one (4% vs. 10%, RR 0.46 [CI 0.32, 0.66]) and three years of follow-up (14% vs. 23%, RR 0.64 [95% CI 0.53, 0.77]). The majority of the studies also showed a greater weight loss in lifestyle intervention participants, with a great variation between studies. Costs per quality-adjusted life-year were lower when the benefits of lifestyle intervention were analyzed over a lifelong time horizon compared to only the period of lifestyle intervention (three years) or to modeling over a ten-year period. CONCLUSION Lifestyle intervention is an efficacious, safe, and cost-effective measure to reduce the risk of progression to type 2 diabetes in people diagnosed with prediabetes. More research is necessary to compare the efficacy of various modes, frequencies, and intensities of lifestyle intervention across studies.

Optimizing medical care for geriatric patients in Austria: defining a top five list of “Choosing Wisely” recommendations using the Delphi technique

PurposeInappropriate use of diagnostic and therapeutic medical procedures is common and potentially harmful for older patients. The Austrian Society of Geriatrics and Gerontology defined a consensus of five recommendations to avoid overuse of medical interventions and to improve care of geriatric patients.MethodsFrom an initial pool of 147 reliable recommendations, 20 were chosen by a structured selection process for inclusion in a Delphi process to define a list of five top recommendations for geriatric medicine. 12 experts in the field of geriatric medicine scored the recommendations in two Delphi rounds.ResultsThe final five recommendations are concerning urinary catheters in elderly patients, percutaneous feeding tubes in patients with advanced dementia, antipsychotics as the first choice to treat behavioral and psychological symptoms of dementia, and screening for breast, colorectal, prostate, or lung cancer, and the use of antimicrobials to treat asymptomatic bacteriuria.ConclusionsThe selected recommendations have the potential to improve medical care for older patients, to reduce side effects caused by unnecessary medical procedures, and to save costs in the health care system.

Leitlinienentwicklung: von der Evidenz zu Empfehlungen Möglichkeiten und Herausforderungen aus Sicht der MethodikerInnen

The development of evidence-based guidelines is an interdisciplinary process in which methodologists play an important role. In addition to creating new or assessing existing systematic reviews as a basis for evidence-based decision making, methodologists can support the entire development process. Due to the increasing complexity of methods and the information overload of available publications, cooperation between the involved experts (especially clinicians and methodologists, but also patient representatives) is essential in order to develop reliable, acceptable and practical guidelines. This article looks at eight key points of the guideline development process (transparency, conflicts of interest, composition of guideline development group, establishing evidence foundation, development and formulation of recommendations, external review and updating) from the perspective of methodologists, and highlights problems, challenges and solution approaches. The earliest possible involvement of methodologists, a clear and a--for non-methodologists--understandable presentation of the best available evidence, the integration of methodologists in the creation and formulation of recommendations (systematic, evidence-based decision-making process) and cooperation between the participating experts are essential to improve the development process of evidence-based guidelines.