Kylie J Thaler

The GRADE approach is reproducible in assessing the quality of evidence of quantitative evidence syntheses

OBJECTIVE We evaluated the inter-rater reliability (IRR) of assessing the quality of evidence (QoE) using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. STUDY DESIGN AND SETTING On completing two training exercises, participants worked independently as individual raters to assess the QoE of 16 outcomes. After recording their initial impression using a global rating, raters graded the QoE following the GRADE approach. Subsequently, randomly paired raters submitted a consensus rating. RESULTS The IRR without using the GRADE approach for two individual raters was 0.31 (95% confidence interval [95% CI] = 0.21-0.42) among Health Research Methodology students (n = 10) and 0.27 (95% CI = 0.19-0.37) among the GRADE working group members (n = 15). The corresponding IRR of the GRADE approach in assessing the QoE was significantly higher, that is, 0.66 (95% CI = 0.56-0.75) and 0.72 (95% CI = 0.61-0.79), respectively. The IRR further increased for three (0.80 [95% CI = 0.73-0.86] and 0.74 [95% CI = 0.65-0.81]) or four raters (0.84 [95% CI = 0.78-0.89] and 0.79 [95% CI = 0.71-0.85]). The IRR did not improve when QoE was assessed through a consensus rating. CONCLUSION Our findings suggest that trained individuals using the GRADE approach improves reliability in comparison to intuitive judgments about the QoE and that two individual raters can reliably assess the QoE using the GRADE system.

Socioeconomic inequalities in non-communicable diseases and their risk factors: an overview of systematic reviews

BackgroundNon-communicable diseases (NCDs) are the largest cause of premature death worldwide. Socioeconomic inequalities contribute to a disparity in the burden of NCDs among disadvantaged and advantaged populations in low (LIC), middle (MIC), and high income countries (HIC). We conducted an overview of systematic reviews to systematically and objectively assess the available evidence on socioeconomic inequalities in relation to morbidity and mortality of NCDs and their risk factors.MethodsWe searched PubMed, The Cochrane Library, EMBASE, SCOPUS, Global Health, and Business Source Complete for relevant systematic reviews published between 2003 and December 2013. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews.ResultsWe screened 3302 abstracts, 173 full-text publications and ultimately included 22 systematic reviews. Most reviews had major methodological shortcomings; however, our synthesis showed that having low socioeconomic status (SES) and/or living in low and middle income countries (LMIC) increased the risk of developing cardiovascular diseases (CVD), lung and gastric cancer, type 2 diabetes, and chronic obstructive pulmonary disease (COPD). Furthermore, low SES increased the risk of mortality from lung cancer, COPD, and reduced breast cancer survival in HIC. Reviews included here indicated that lower SES is a risk factor for obesity in HIC, but this association varied by SES measure. Early case fatalities of stroke were lower and survival of retinoblastoma was higher in MIC compared to LIC.ConclusionsThe current evidence supports an association between socioeconomic inequalities and NCDs and risk factors for NCDs. However, this evidence is incomplete and limited by the fairly low methodological quality of the systematic reviews, including shortcomings in the study selection and quality assessment process.

COMPARATIVE EFFECTIVENESS OF SECOND-GENERATION ANTIDEPRESSANTS FOR ACCOMPANYING ANXIETY, INSOMNIA, AND PAIN IN DEPRESSED PATIENTS: A SYSTEMATIC REVIEW

Patients with major depressive disorder (MDD) often suffer from accompanying symptoms that influence the choice of pharmacotherapy with second‐generation antidepressants (SGAs). We conducted a systematic review to determine the comparative effectiveness of citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, desvenlafaxine, duloxetine, venlafaxine, bupropion, mirtazapine, nefazodone, and trazodone, for accompanying anxiety, insomnia, and pain in patients with MDD.

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.

Bach Flower Remedies for psychological problems and pain: a systematic review

BackgroundBach Flower Remedies are thought to help balance emotional state and are commonly recommended by practitioners for psychological problems and pain. We assessed whether Bach Flower Remedies (BFRs) are safe and efficacious for these indications by performing a systematic review of the literature.MethodsWe searched MEDLINE®, Embase, AMED, and the Cochrane Library from inception until June 2008 and performed a hand-search of references from relevant key articles. For efficacy, we included all prospective studies with a control group. For safety, we also included retrospective, observational studies with more than 30 subjects. Two authors abstracted data and determined risk of bias using a recognised rating system of trial quality.ResultsFour randomised controlled trials (RCTs) and two additional retrospective, observational studies were identified and included in the review. Three RCTs of BFRs for students with examination anxiety, and one RCT of BFRs for children with attention-deficit hyperactivity disorder (ADHD) showed no overall benefit in comparison to placebo. Due to the number and quality of the studies the strength of the evidence is low or very low. We did not find any controlled prospective studies regarding the efficacy of BFRs for pain. Only four of the six studies included for safety explicitly reported adverse events.ConclusionMost of the available evidence regarding the efficacy and safety of BFRs has a high risk of bias. We conclude that, based on the reported adverse events in these six trials, BFRs are probably safe. Few controlled prospective trials of BFRs for psychological problems and pain exist. Our analysis of the four controlled trials of BFRs for examination anxiety and ADHD indicates that there is no evidence of benefit compared with a placebo intervention.

Efficacy and safety of anakinra for the treatment of rheumatoid arthritis: an update of the Oregon Drug Effectiveness Review Project

Objective To systematically review the general and comparative efficacy and safety of anakinra for rheumatoid arthritis. Methods We searched MEDLINE®, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to April 2009. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database. For efficacy we included randomized controlled trials (RCTs) comparing anakinra with placebo or other biologics. For safety both experimental and observational studies were eligible. Two persons independently reviewed abstracts and full text articles and extracted relevant data. Results We included data from 3 RCTs comparing anakinra with placebo for rheumatoid arthritis (RA). The pooled relative risk (RR) of an ACR50 (American College of Rheumatology) response for anakinra compared with placebo is 2.28 (95% CI 1.41 to 3.67). Adjusted indirect comparisons of ACR50 response rates of anakinra and anti-TNF agents showed a RR of 0.67 (95% CI 0.38 to 1.17) favoring the anti-TNF drugs. This result did not reach statistical significance. For safety, we included 9 experimental and observational studies of 24 weeks to 3 years duration. Up to 30% of patients withdrew from the studies due to adverse events. 67.2% (95% CI 38.7 to 95.7) of patients experienced an injection site reaction. Conclusions Anakinra is an effective drug for treating RA. Indirect comparisons with adalimumab, etanercept and infliximab, however, showed a trend towards greater efficacy for the anti-TNF drugs. Anakinra also seems to be associated with comparably high rates of injection site reactions. These results should be taken into account when considering biologic therapy for patients with RA.

The general and comparative efficacy and safety of duloxetine in major depressive disorder: a systematic review and meta-analysis.

Background: Second-generation antidepressants dominate the management of patients with major depressive disorder (MDD). Evidence on the general and comparative benefits and harms is still accruing.Objective: To systematically review the general and comparative efficacy and safety of duloxetine for the treatment of acute-phase MDD in adults.Data Sources: We conducted a search of MEDLINE, Embase, PsychLit, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to July 2009, as well as manually searching reference lists of pertinent review articles and exploring the Center for Drug Evaluation and Research database to identify unpublished research.Study Selection: For efficacy, randomized controlled trials (RCTs) comparing duloxetine with placebo or second-generation antidepressants were included. For safety, both experimental and observational studies were eligible.Data Extraction: Abstracts and full-text articles were independently reviewed by two people, one investigator extracted relevant data, and a senior reviewer checked data for completeness and accuracy.Results: We included 36 experimental and observational studies and, where sufficient data were available, meta-analyses of RCTs were conducted. Findings indicated that duloxetine is an effective treatment option for acute-phase MDD, with a tolerability profile similar to other second-generation antidepressants. No substantial differences in efficacy and safety appear to exist when duloxetine is compared with other second-generation antidepressants. Overall, about 40% of patients treated with duloxetine achieved remission. Compared with other treatments, duloxetine had frequently higher rates of nausea, vomiting and dry mouth; however, these differences did not lead to higher discontinuation rates compared with selective serotonin reuptake inhibitors as a class. There is insufficient evidence to draw conclusions about rare but severe adverse events.Conclusions: Current evidence does not warrant the choice of duloxetine over other second-generation antidepressants based on greater efficacy or safety for patients with acute-phase MDD with or without accompanying symptoms such as pain.

Adjunct ultrasonography for breast cancer screening in women at average risk: a systematic review

BACKGROUND Screening with mammography has the ability to detect breast cancer at an early stage but misses some cancers. Supporters of adjunct ultrasonography to the screening regimen argue that it might be a safe and inexpensive approach to reduce the false-negative rates of screening. Critics are concerned that adjunct ultrasonography will also increase the rate of false-positive findings and can lead to unnecessary biopsies and treatments in women at average risk. AIMS The purpose of this review was to systematically assess the comparative benefits and harms of mammography with adjunct breast ultrasonography and mammography only in breast cancer screening. METHODS We searched multiple electronic databases and the Cochrane Breast Cancer Groups Specialised Register (from 1995 to February 2012). To detect ongoing or unpublished studies, we searched trial registries and multiple sources of grey literature. Two researchers independently reviewed all abstracts and full-text articles against pre-defined eligibility criteria. We dually rated the risk of bias of studies and the strength of evidence based on established guidance. RESULTS We did not detect any controlled studies that provide evidence for (or against) the use of adjunct ultrasonography for screening in women at average risk for breast cancer. Extrapolations of results from women at elevated risk for breast cancer indicate that the false-positive rates in women at average risk who were recalled because of positive ultrasonographies will exceed 98%. In women with dense or very dense breast tissue, the evidence regarding the use of adjunct ultrasonography is not conclusive. CONCLUSIONS No methodologically sound evidence is available justifying the routine use of ultrasonography as an adjunct screening tool in women at average risk for breast cancer. IMPLICATIONS FOR PRACTICE Clinicians should not use ultrasonography as a screening tool for breast cancer screening on a routine basis. The use should be limited to women with dense breasts for whom the accuracy of mammography is low, or for diagnostic purposes.

How Should Primary Care Doctors Select Which Antidepressants to Administer

Clinicians can choose among various second-generation antidepressants for treating depressive disorders, such as major depressive disorder, subsyndromal depression, or dysthymia. Systematic reviews indicate that available drugs differ in frequency of administration, costs, and the risks of some adverse events but have similar efficacy for treating major depressive disorder. Furthermore, evidence does not support the choice of one antidepressant over another based on accompanying symptoms, such anxiety, insomnia, or pain. Available studies provide little guidance for clinicians about the benefits of second-generation antidepressants for treating dysthymia and subsyndromal depression. Evidence is also unclear about the comparative risks of serious adverse events, such as suicidality, seizures, fractures, increased bleeding, or serotonin syndrome. This article summarizes the best available evidence regarding comparative benefits and harms of second-generation antidepressants for treating depressive disorders.

Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review

Being male or female is an important determinant of risks for certain diseases, patterns of illness and life expectancy. Although differences in risks for and prognoses of several diseases have been well documented, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. The objective of this umbrella review was to determine whether clinically relevant differences in efficacy and safety of commonly prescribed medications exist between men and women. We retrieved all available systematic reviews of the Oregon Drug Effectiveness Review Project published before January 2010. Two persons independently reviewed each report to identify relevant studies. We dually abstracted data from the original publications into standardized forms. We synthesized the available evidence for each drug class and rated its quality applying the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Findings, based on 59 studies and data of more than 250,000 patients suggested that for the majority of drugs no substantial differences in efficacy and safety exist between men and women. Some clinically important exceptions, however, were apparent: women experienced substantially lower response rates with newer antiemetics than men (45% vs. 58%; relative risk 1.49, 95% confidence interval 1.35–1.64); men had higher rates of sexual dysfunction than women while on paroxetine for major depressive disorder; women discontinued lovastatin more frequently than men because of adverse events. Overall, for the majority of drugs sex does not appear to be a factor that has to be taken into consideration when choosing a drug treatment. The available body of evidence, however, was limited in quality and quantity, confining the range and certainty of our conclusions.