Theodore Lytras

Effectiveness of Computerized Decision Support Systems Linked to Electronic Health Records: A Systematic Review and Meta-Analysis

We systematically reviewed randomized controlled trials (RCTs) assessing the effectiveness of computerized decision support systems (CDSSs) featuring rule- or algorithm-based software integrated with electronic health records (EHRs) and evidence-based knowledge. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Abstracts of Reviews of Effects. Information on system design, capabilities, acquisition, implementation context, and effects on mortality, morbidity, and economic outcomes were extracted. Twenty-eight RCTs were included. CDSS use did not affect mortality (16 trials, 37395 patients; 2282 deaths; risk ratio [RR] = 0.96; 95% confidence interval [CI] = 0.85, 1.08; I(2) = 41%). A statistically significant effect was evident in the prevention of morbidity, any disease (9 RCTs; 13868 patients; RR = 0.82; 95% CI = 0.68, 0.99; I(2) = 64%), but selective outcome reporting or publication bias cannot be excluded. We observed differences for costs and health service utilization, although these were often small in magnitude. Across clinical settings, new generation CDSSs integrated with EHRs do not affect mortality and might moderately improve morbidity outcomes.

Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis

ABSTRACT Introduction: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1–36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6–48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.

Occupational Asthma guidelines: a systematic quality appraisal using the AGREE II instrument

The quality of guidelines is often modest and highly variable. We searched the Medline database for occupational asthma (OA) guidelines meeting our inclusion criteria and undertook a systematic appraisal of them. Six appraisers independently evaluated these guidelines using the AGREE II (Appraisal of Guidelines, Research and Evaluation II) instrument. Standardised scores for each domain and for overall quality were calculated, as well as intraclass correlation coefficients to assess agreement among appraisers. Seven relevant guidelines were identified. Three were based on a systematic review of the evidence. Most guidelines scored high on the domains ‘Scope and purpose’ and ‘Clarity and presentation’, but scores on the other domains were variable. The lowest scores were for ‘Applicability’, suggesting that guideline developers did not pay sufficient attention to practical problems affecting the implementation of their recommendations. We also observed a trend toward improved scores in guidelines published after 2000. Inter-rater agreement was good for most domains, and particularly for ‘Rigour of development’. This domain was most strongly correlated with the overall assessment scores, together with ‘Scope and purpose’ and ‘Editorial independence’. The quality of OA guidelines is variable, both within and across guidelines. There is significant room for improvement, and greater efforts to produce high-quality guidelines are warranted, in order to assist clinical decision-making.

Intravenous versus oral iron for the treatment of anemia in inflammatory bowel disease: A systematic review and meta-analysis of randomized controlled trials

AbstractAnemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients.We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trials risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models.Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention.IV iron appears to be more effective and better tolerated than oral iron for the treatment of IBD-associated anemia.

Fatal cases associated with pandemic influenza A (H1N1) reported in Greece.

ABSTRACT Between 18 May 2009 and 3 May 2010, a total of 149 fatal cases associated with pandemic influenza A (H1N1) were reported in Greece. Detailed case-based epidemiological information was available for the large majority of fatal cases. The time distribution follows an epidemic curve with a peak in the beginning of December 2009 and a second peak one month later. This is similar to that of laboratory confirmed cases and influenza-like illness cases from our sentinel surveillance system, with two weeks delay. The most commonly reported underlying conditions were chronic cardiovascular disease and immunosuppression, while the most frequently identified risk factor was obesity. These findings should be taken into consideration, when vaccination strategies are employed.

Interventions to increase seasonal influenza vaccine coverage in healthcare workers: A systematic review and meta-regression analysis

ABSTRACT Influenza vaccination is recommended for healthcare workers (HCWs), but coverage is often low. We reviewed studies evaluating interventions to increase seasonal influenza vaccination coverage in HCWs, including a meta-regression analysis to quantify the effect of each component. Fourty-six eligible studies were identified. Domains conferring a high risk of bias were identified in most studies. Mandatory vaccination was the most effective intervention component (Risk Ratio of being unvaccinated [RRunvacc] = 0.18, 95% CI: 0.08–0.45), followed by “soft” mandates such as declination statements (RRunvacc = 0.64, 95% CI: 0.45–0.92), increased awareness (RRunvacc = 0.83, 95% CI: 0.71–0.97) and increased access (RRunvacc = 0.88, 95% CI: 0.78–1.00). For incentives the difference was not significant, while for education no effect was observed. Heterogeneity was substantial (τ2 = 0.083). These results indicate that effective alternatives to mandatory HCWs influenza vaccination do exist, and need to be further explored in future studies.

Influenza vaccine effectiveness against laboratory confirmed influenza in Greece during the 2013–2014 season: A test-negative study

BACKGROUND In 2013-2014 Greece experienced a resurgence of severe influenza cases, coincidental with a shift to H1N1pdm09 predominance. We sought to estimate Vaccine Effectiveness (VE) for this season using available surveillance data from hospitals (including both inpatients and outpatients). METHODS Swab samples were sent by hospital physicians to one of three laboratories, covering the entire country, to be tested for influenza using RT-PCR. The test-negative design was employed, with patients testing positive serving as cases and those testing negative serving as controls. VE was estimated using logistic regression, adjusted for age group, sex, region and calendar time, with further adjustment for unknown vaccination status using inverse response propensity weights. Additional age group stratified estimates and subgroup estimates of VE against H1N1pdm09 and H3N2 were calculated. RESULTS Out of 1310 patients with known vaccination status, 124 (9.5%) were vaccinated, and 543 patients (41.5%) tested positive for influenza. Adjusted VE was 34.5% (95% CI: 4.1-55.3%) against any influenza, and 56.7% (95% CI: 22.8-75.7%) against H1N1pdm09. VE estimates appeared to be higher for people aged 60 and older, while in those under 60 there was limited evidence of effectiveness. Isolated circulating strains were genetically close to the vaccine strain, with limited evidence of antigenic drift. CONCLUSIONS These results suggest a moderate protective effect of the 2013-2014 influenza vaccine, mainly against H1N1pdm09 and in people aged 60 and over. Vaccine coverage was very low in Greece, even among groups targeted for vaccination, and substantial efforts should be made to improve it. VE can and should be routinely monitored, and the results taken into account when deciding on influenza vaccine composition for next season.

Statin use and breast cancer: do we need more evidence and what should this be?

3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been proved highly effective treatments for primary and secondary prevention of cardiovascular diseases. Despite widespread and long-term use of statins, there is still a debate concerning their association with cancer at various sites, including breast. As of today, the accumulated epidemiological evidence does not support the hypothesis that statin use affects the risk of developing breast cancer when taken at low doses for managing hypercholesterolemia. However, current evidence cannot exclude an increased risk of breast cancer with statin use in subsets of individuals, for example, the elderly. On the other hand, some studies show that statins might be useful to prevent recurrence and improve survival in patients already suffering from certain breast cancer types. They could also be combined with certain anticancer drugs and potentiate their effects, ameliorate their side effects or prevent the development of resistance. Further research is warranted to clarify these issues.

Evaluation of Tuberculosis Underreporting in Greece through Comparison with Anti-Tuberculosis Drug Consumption

Surveillance is an integral part of tuberculosis (TB) control. Greece has a low TB notification rate, but there are doubts about underreporting. Examining anti-TB drug consumption is a way to validate the results of surveillance and estimate TB burden in the country. We used surveillance data from 2004 to 2008 to calculate the average prescribed treatment duration with the first-line anti-TB drugs isoniazid, rifampicin, ethambutol and pyrazinamide. We then obtained the best available data on consumption of these drugs, and calculated the number of treated cases to which these quantities correspond. We thus estimated underreporting at around 80% (77–81%), and annual TB incidence at about 30 cases per 100,000 population, five times over the notification rate. Underreporting was found to be constant over the study period, while incidence followed a decreasing trend. In addition we estimated that one person receives chemoprophylaxis for latent tuberculosis infection (LTBI) for every three TB cases. These results indicate the need for a comprehensive plan to improve TB surveillance and TB contact tracing in Greece, especially in light of the economic crisis affecting the country since 2009.

On the criteria used for assessing the risk of bias in randomized trials included in systematic reviews and meta-analyses addressing adverse effects

Systematic reviews and meta-analyses are a valuable tool to answer research questions, generate recommendations and influence health policy in an evidence-based manner [1]. However, flaws in the design, conduct, analysis, and reporting of the studies that are included in a systematic review may distort estimates of the true intervention effect in terms of magnitude and/or direction (i.e. introduce bias), mislead the analysis and conclusions of the systematic review, and adversely influence clinical practice and health policy decisions [2]. Based on a combination of empirical and theoretical considerations, the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group proposed a set of criteria for assessing the risk of bias in RCTs, which address the following key domains: (1) sequence generation, (2) allocation concealment, (3) blinding of participants, personnel, and outcome assessors, (4) incomplete outcome data, (5) selective outcome reporting, and (6) other sources of bias (e.g., extreme baseline imbalance in prognostic factors, inappropriate influence of the funding source, etc) [3]. The Cochrane Collaboration’s domain-based approach has proven to be very useful; it has been widely adopted, and used in hundreds of systematic reviews and metaanalyses. However, the Cochrane Adverse Effects Methods Group proposed few additional criteria for assessing the risk of bias in RCTs selected for inclusion in systematic reviews addressing adverse effects (AEs) [4] including methods for monitoring and detecting adverse effects [4] (p. 8). The particular item for judging risk of bias was: Were the methods used for monitoring adverse effects reported? Use of prospective or routine monitoring; spontaneous reporting; patient checklist, questionnaire or diary; systematic survey of patients? [4] (p. 9). As a result, this criterion is increasingly used in the literature, with researchers considering studies providing spontaneous reporting of AEs (passive surveillance) as of higher risk of bias than studies actively monitoring for drug AEs [5–8]. We argue that this proposed risk-of-bias criterion (based on the approach used for monitoring AEs) is methodologically incorrect, and could lead reviewers to assess potentially fair (unbiased) clinical trials as having a high risk of bias. It is true that the methods used for monitoring AEs have a major influence on the detected event rates in a trial, with passive surveillance of harms leading to fewer recorded AEs than active surveillance [9, 10]. However, the relative effect measure in a trial (e.g. the ratio of the observed event rates in the comparison groups) will not change if these event rates are underestimated, to the same degree, in each comparison group. Therefore less intensive monitoring methods, although they may lead to lower observed rates of AEs, do not constitute a source of bias, but rather a cause of imprecision. A potential source of bias must be able to produce results that depart systematically & Stefanos Bonovas sbonovas@gmail.com