Yanting Luo

The diagnostic performance of CT-derived fractional flow reserve for evaluation of myocardial ischaemia confirmed by invasive fractional flow reserve: a meta-analysis

AIM To review the literature on the diagnostic accuracy of CT-derived fractional flow reserve (FFRCT) for the evaluation of myocardial ischaemia in patients with suspected or known coronary artery disease, with invasive fractional flow reserve (FFR) as the reference standard. MATERIALS AND METHODS A PubMed, EMBASE, and Cochrane cross-search was performed. The pooled diagnostic accuracy of FFRCT, with FFR as the reference standard, was primarily analysed, and then compared with that of CT angiography (CTA). The thresholds to diagnose ischaemia were FFR ≤0.80 or CTA ≥50% stenosis. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. RESULTS Three multicentre studies (NXT Trial, DISCOVER-FLOW study and DeFACTO study) were included, examining 609 patients and 1050 vessels. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) for FFRCT were 89% (85-93%), 71% (65-75%), 70% (65-75%), 90% (85-93%), 3.31 (1.79-6.14), 0.16 (0.11-0.23), and 21.21 (9.15-49.15) at the patient-level, and 83% (78-63%), 78% (75-81%), 61% (56-65%), 92% (89-90%), 4.02 (1.84-8.80), 0.22 (0.13-0.35), and 19.15 (5.73-63.93) at the vessel-level. At per-patient analysis, FFRCT has similar sensitivity but improved specificity, PPV, NPV, LR+, LR-, and DOR versus those of CTA. At per-vessel analysis, FFRCT had a slightly lower sensitivity, similar NPV, but improved specificity, PPV, LR+, LR-, and DOR compared with those of CTA. The area under the summary receiver operating characteristic curves for FFRCT was 0.8909 at patient-level and 0.8865 at vessel-level, versus 0.7402 for CTA at patient-level. CONCLUSIONS FFRCT, which was associated with improved diagnostic accuracy versus CTA, is a viable alternative to FFR for detecting coronary ischaemic lesions.

A head-to-head comparison of homocysteine and cystatin C as pre-procedure predictors for contrast-induced nephropathy in patients undergoing coronary computed tomography angiography

BACKGROUND Homocysteine is a potential predictor for contrast-induced nephropathy (CIN). We aimed to compare homocysteine with cystatin C as pre-procedure predictors for CIN in patients undergoing coronary computed tomography angiography (CCTA). METHODS A total of 580 consecutive patients were enrolled. Concentrations of plasma homocysteine and serum cystatin C were measured before CCTA. CIN is defined as an elevation of creatinine by ≥ 25% or ≥ 0.5mg/dl from baseline within 48h. Receiver operating characteristic curves, Pearson correlation coefficients and logistic regression analysis were used to evaluate the efficiency of potential predictors. RESULTS Fifty-seven (9.83%) patients developed CIN. Concentrations of homocysteine (19.35 ± 4.32 μmol/l vs. 13.42 ± 3.96 μmol/l, p<0.001) and cystatin C (1.20 ± 0.21 mg/dl vs. 0.99 ± 0.15 mg/dl, p<0.001) increased significantly in CIN subjects. CIN was predicted by homocysteine (AUC 0.829, p<0.001) and cystatin C (AUC 0.774, p<0.001), while creatinine was not predictive. Both homocysteine and cystatin C had positive correlation with ΔCreatinine48h-0 (p<0.001) and negative correlation with ΔeGFR48h-0 (p<0.001). Regression analysis confirmed that increased baseline homocysteine [OR: 1.262 (1.123, 2.554), p<0.001] and cystatin C [OR: 1.565 (1.380, 1.775), p<0.001] were independent predictors for CIN. CONCLUSIONS Homocysteine, with similar predictive value compared to cystatin C, was an independent biomarker for predicting CIN before CCTA examination.

Trimetazidine improves exercise tolerance in patients with ischemic heart disease : A meta-analysis.

AimThis study aimed to evaluate the effect of trimetazidine (TMZ) in addition to standard treatment on exercise tolerance in patients with ischemic heart disease (IHD).MethodsStudies were identified via a systematic search of PubMed, Embase, Cochrane Library, and the Chinese CNKI databases from January 1978 to January 2015. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Random or fixed effects models were used to estimate pooled mean differences in total exercise duration (TED), peak oxygen uptake (pVO2), metabolic equivalent system (METS), and 6-minute walking test (6-MWT).ResultsIn all, 16 randomized controlled trials (RCTs) consisting of 2,004 participants were included. Pooled results showed that TMZ treatment significantly improved TED (WMD: 37.35, 95 % CI: 25.58–49.13, p < 0.00001), pVO2 (WMD: 2.41, 95 % CI: 1.76–3.06, p < 0.00001), METS (WMD: 1.33, 95 % CI: 0.38–2.28, p = 0.006), and 6-WMT (WMD: 62.46, 95 % CI: 35.86–89.05, p < 0.001) in all patients with IHD. Subgroup analysis showed that TMZ significantly increased TED in nondiabetic participants (WMD 34.77, 95 % CI: 22.28–47.25, p < 0.001), but not in diabetic participants (WMD: 40.36, 95 % CI: − 18.76–99.48, p = 0.18). And, subgroup analysis of TED by intervention duration suggested that there is no statistically difference between the 3-month and 6-month periods (WMD: 35.47, 95 %CI: 18.35–52.60, p < 0.0001 and WMD: 49.94, 95 %CI: 44.69–55.19, p < 0.00001). In addition, TMZ improved TED (WMD: 50.01, 95 % CI: 44.77–55.25 and WMD: 24.20, 95 % CI: 12.72–35.68) in IHD patients with or without heart failure (HF), respectively.ConclusionAddition of TMZ to standard treatment significantly improved exercise tolerance in patients with IHD, and IHD patients with HF may experience even more benefits. However, there is insufficient evidence to show that TMZ has beneficial effects in participants with diabetes.ZusammenfassungZielZiel der vorliegenden Studie war es, die Wirkung von Trimetazidin (TMZ) zusätzlich zu der Standardtherapie auf die Belastungstoleranz bei Patienten mit ischämischer Herzerkrankung („ischemic heart disease“, IHD) zu untersuchen.MethodenStudien wurden über eine systematische Suche in den Datenbanken PubMed, Embase, Cochrane Library und in der chinesischen CNKI (China National Knowledge Infrastructure) von Januar 1978 bis Januar 2015 gesucht. Die Datenerfassung, -synthese und statistische Analyse erfolgten mit Standardmethoden der Metaanalyse. Random- oder Fixed-Effects-Modelle wurden eingesetzt, um die gepoolten mittleren Differenzen bei der Gesamtbelastungsdauer („total exercise duration“, TED), der Spitzensauerstoffaufnahme („peak oxygen uptake“, pVO2), dem metabolischen Äquivalentsystem („metabolic equivalent system“, METS) und dem 6-min-Gehtest („6-minute walking test“, 6-MWT) abzuschätzen.ErgebnisseEs wurden 16 randomisierte kontrollierte Studien (RCT) mit 2004 Teilnehmern in die Auswertung eingeschlossen. Die gepoolten Ergebnisse zeigten, dass die TMU-Behandlung zu einer signifikanten Verbesserung der TED (gewichtete mittlere Differenz, WMD: 37,35; 95 %-Konfidenzintervall, 95%-KI: 25,58–49,13; p < 0,00001), der pVO2 (WMD: 2,41; 95 %-KI: 1,76–3,06; p < 0,00001), des METS (WMD: 1,33; 95 %-KI: 0,38–2,28; p = 0,006) und des 6-WMT (WMD: 62,46; 95 %-KI: 35,86–89,05; p < 0,001) bei allen Patienten mit IHD führte.Die Subgruppenanalyse ergab, dass TMZ die TED bei Teilnehmern ohne Diabetes mellitus signifikant erhöhte (WMD 34,77; 95 %-KI: 22,28–47,25; p < 0,001), nicht aber bei Teilnehmern mit Diabetes (WMD: 40,36; 95 %-KI: − 18,76–99,48; p = 0,18). Und aus der Subgruppenanalyse der TED nach Interventionsdauer ergaben sich Hinweise darauf, dass statistisch kein Unterschied zwischen der 3-monatigen und der 6-monatigen Dauer bestehe (WMD: 35,47; 95 %-KI: 18,35–52,60; p < 0,0001 bzw. WMD: 49,94; 95 %-KI: 44,69–55,19; p < 0,00001). Außerdem zeigte sich eine Verbesserung der TED unter TMZ (WMD: 50,01; 95 %-KI: 44,77–55,25 bzw. WMD: 24,20; 95 %-KI: 12,72–35,68) bei IHD-Patienten mit bzw. ohne Herzinsuffizienz.SchlussfolgerungDie zusätzliche Gabe von TMZ zur Standardbehandlung verbesserte die Belastungstoleranz signifikant bei Patienten mit ischämischer Herzerkrankung. IHD-Patienten mit Herzinsuffizienz haben möglicherweise noch einen größeren Nutzen. Es gibt jedoch keine ausreichende Evidenz dafür, dass TMZ einen Nutzeffekt bei Teilnehmern mit Diabetes mellitus habe.

Preprocedure and Postprocedure Predictive Values of Serum β2-Microglobulin for Contrast-Induced Nephropathy in Patients Undergoing Coronary Computed Tomography Angiography: A Comparison With Creatinine-Based Parameters and Cystatin C.

Objective This study aimed to investigate the values of serum &bgr;2-microglobulin to predict contrast-induced nephropathy (CIN) before and early after coronary computed tomography angiography (CCTA), comparing with creatinine-based parameters and cystatin C. Methods A total of 424 patients were enrolled. Serum &bgr;2-microglobulin, cystatin C, and creatinine were measured at 0, 24, and 48 hours of CCTA. Contrast-induced nephropathy was defined as an elevation of serum creatinine level by 25% or higher or 0.5 mg/dL or greater from baseline within 48 hours. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease study equation. Receiver operating characteristic curves and multivariate logistic regression analysis were used to detect the efficiency of biomarkers in predicting CIN. Results Fifty-two subjects (12.26%) developed CIN. Before CCTA, CIN was predicted by both baseline &bgr;2-microglobulin (area under the receiver operating characteristic curve [AUC], 0.791; P < 0.001) and cystatin C (AUC, 0.781; P < 0.001), whereas creatinine and eGFR were not predictive. After CCTA, CIN was predicted by both the absolute post-CCTA levels of &bgr;2-microglobulin, cystatin C, creatinine, and eGFR (AUC, 0.842 vs 0.961 vs 0.691 vs 0.688 at 24 hours, P < 0.001; and 0.937 vs 1.000 vs 0.908 vs 0.898 at 48 hours, P < 0.001) and their relative changes (&Dgr;) to baseline (AUC, 0.677 vs 0.846 vs 0.850 vs 0.844 at 24 hours, P < 0.001; and 0.731 vs 0.968 vs 0.984 vs 0.966 at 48 hours, P < 0.001). Multivariate regression analysis confirmed that baseline &bgr;2-microglobulin (odds ratio, 2.137; 95% confidence interval, 1.805–3.109; P < 0.001) and cystatin C (odds ratio, 1.873; 95% confidence interval, 1.667–2.341; P = 0.003) were independent predictors for CIN. Conclusions Serum &bgr;2-microglobulin, with values superior to creatinine-based parameters and similar with cystatin C, was a useful biomarker for the prediction of CIN at pre-CCTA and early post-CCTA.

Effect of potassium supplementation on vascular function: A meta-analysis of randomized controlled trials

BACKGROUND Effects of potassium supplementation on vascular function remain conflicting. This meta-analysis aimed to summarized current literature to fill the gaps in knowledge. METHODS A literature search was performed on PubMed database through April, 2016. The measurements of vascular function included pulse wave velocity (PWV), augmentation index (AI), pulse pressure (PP), flow mediated dilatation (FMD), glycerol trinitrate responses (GTN), and intercellular cell adhesion molecule-1 (ICAM-1). Data were pooled as standardized mean difference (SMD) with 95% confidence intervals. RESULTS Seven randomized controlled trials examining 409 participants were included, with dosage of potassium ranging from 40 to 150mmol/day, and duration of intervention from 6days to 12months. Pooling results revealed a significant improvement in PP (SMD -0.280, 95% CI -0.493 to -0.067, p=0.010), but no improvement in PWV (SMD -0.342, 95% CI -1.123 to 0·440, p=0.391), AI (SMD -0.114, 95% CI -0.282 to 0.054, p=0.184), FMD (SMD 0·278, 95% CI -0.321 to 0.877, p=0.363), GTN (SMD -0.009, 95% CI -0.949 to 0.930, p=0.984), and ICAM-1 (SMD -0.238, 95% CI -0.720 to 0.244, p=0.333). CONCLUSIONS Potassium supplementation was associated with significant improvement of PP, rather than other measurements of vascular function. However, the small number of researches and wide variation of evidences make it difficult to make a definitive conclusion.

Trimetazidine improves exercise tolerance in patients with ischemic heart disease

AimThis study aimed to evaluate the effect of trimetazidine (TMZ) in addition to standard treatment on exercise tolerance in patients with ischemic heart disease (IHD).MethodsStudies were identified via a systematic search of PubMed, Embase, Cochrane Library, and the Chinese CNKI databases from January 1978 to January 2015. Data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Random or fixed effects models were used to estimate pooled mean differences in total exercise duration (TED), peak oxygen uptake (pVO2), metabolic equivalent system (METS), and 6-minute walking test (6-MWT).ResultsIn all, 16 randomized controlled trials (RCTs) consisting of 2,004 participants were included. Pooled results showed that TMZ treatment significantly improved TED (WMD: 37.35, 95 % CI: 25.58–49.13, p < 0.00001), pVO2 (WMD: 2.41, 95 % CI: 1.76–3.06, p < 0.00001), METS (WMD: 1.33, 95 % CI: 0.38–2.28, p = 0.006), and 6-WMT (WMD: 62.46, 95 % CI: 35.86–89.05, p < 0.001) in all patients with IHD. Subgroup analysis showed that TMZ significantly increased TED in nondiabetic participants (WMD 34.77, 95 % CI: 22.28–47.25, p < 0.001), but not in diabetic participants (WMD: 40.36, 95 % CI: − 18.76–99.48, p = 0.18). And, subgroup analysis of TED by intervention duration suggested that there is no statistically difference between the 3-month and 6-month periods (WMD: 35.47, 95 %CI: 18.35–52.60, p < 0.0001 and WMD: 49.94, 95 %CI: 44.69–55.19, p < 0.00001). In addition, TMZ improved TED (WMD: 50.01, 95 % CI: 44.77–55.25 and WMD: 24.20, 95 % CI: 12.72–35.68) in IHD patients with or without heart failure (HF), respectively.ConclusionAddition of TMZ to standard treatment significantly improved exercise tolerance in patients with IHD, and IHD patients with HF may experience even more benefits. However, there is insufficient evidence to show that TMZ has beneficial effects in participants with diabetes.ZusammenfassungZielZiel der vorliegenden Studie war es, die Wirkung von Trimetazidin (TMZ) zusätzlich zu der Standardtherapie auf die Belastungstoleranz bei Patienten mit ischämischer Herzerkrankung („ischemic heart disease“, IHD) zu untersuchen.MethodenStudien wurden über eine systematische Suche in den Datenbanken PubMed, Embase, Cochrane Library und in der chinesischen CNKI (China National Knowledge Infrastructure) von Januar 1978 bis Januar 2015 gesucht. Die Datenerfassung, -synthese und statistische Analyse erfolgten mit Standardmethoden der Metaanalyse. Random- oder Fixed-Effects-Modelle wurden eingesetzt, um die gepoolten mittleren Differenzen bei der Gesamtbelastungsdauer („total exercise duration“, TED), der Spitzensauerstoffaufnahme („peak oxygen uptake“, pVO2), dem metabolischen Äquivalentsystem („metabolic equivalent system“, METS) und dem 6-min-Gehtest („6-minute walking test“, 6-MWT) abzuschätzen.ErgebnisseEs wurden 16 randomisierte kontrollierte Studien (RCT) mit 2004 Teilnehmern in die Auswertung eingeschlossen. Die gepoolten Ergebnisse zeigten, dass die TMU-Behandlung zu einer signifikanten Verbesserung der TED (gewichtete mittlere Differenz, WMD: 37,35; 95 %-Konfidenzintervall, 95%-KI: 25,58–49,13; p < 0,00001), der pVO2 (WMD: 2,41; 95 %-KI: 1,76–3,06; p < 0,00001), des METS (WMD: 1,33; 95 %-KI: 0,38–2,28; p = 0,006) und des 6-WMT (WMD: 62,46; 95 %-KI: 35,86–89,05; p < 0,001) bei allen Patienten mit IHD führte.Die Subgruppenanalyse ergab, dass TMZ die TED bei Teilnehmern ohne Diabetes mellitus signifikant erhöhte (WMD 34,77; 95 %-KI: 22,28–47,25; p < 0,001), nicht aber bei Teilnehmern mit Diabetes (WMD: 40,36; 95 %-KI: − 18,76–99,48; p = 0,18). Und aus der Subgruppenanalyse der TED nach Interventionsdauer ergaben sich Hinweise darauf, dass statistisch kein Unterschied zwischen der 3-monatigen und der 6-monatigen Dauer bestehe (WMD: 35,47; 95 %-KI: 18,35–52,60; p < 0,0001 bzw. WMD: 49,94; 95 %-KI: 44,69–55,19; p < 0,00001). Außerdem zeigte sich eine Verbesserung der TED unter TMZ (WMD: 50,01; 95 %-KI: 44,77–55,25 bzw. WMD: 24,20; 95 %-KI: 12,72–35,68) bei IHD-Patienten mit bzw. ohne Herzinsuffizienz.SchlussfolgerungDie zusätzliche Gabe von TMZ zur Standardbehandlung verbesserte die Belastungstoleranz signifikant bei Patienten mit ischämischer Herzerkrankung. IHD-Patienten mit Herzinsuffizienz haben möglicherweise noch einen größeren Nutzen. Es gibt jedoch keine ausreichende Evidenz dafür, dass TMZ einen Nutzeffekt bei Teilnehmern mit Diabetes mellitus habe.

e0184 The protection effects of trimetazidine on rats myocardial infraction

Objective To observe the myocardial protection effects of trimetazidine on Sprague-Dawley (SD) rats with myocardial infarctions (MI). Methods 90 SD rats were randomly assigned to normal control group (NL, n=30), Trimetazidine group (T, n=30) and sham-operated group (S, n=30). The MI model was set up in SD rats by permanent ligation of the left anterior descending coronary artery. In S group suture was through the left anterior descending coronary artery without ligation. Before and after MI, in NL group/S group and T group normal saline and Trimetazidine (0.3 mg/kg) were separately given by gavage. The changes of serum cTnI were observed at 8, 24, 48 h after MI. The changes of serum cTnI in S group was only observed at 24th hour after operations. In 1 week, 2 weeks and 4 weeks after treatment, the areas of myocardial infarction were analysed, and isovolumic systolic left ventricular maximum rate of pressure rise (+dp/dtmax) and isovolumic diastolic left ventricular maximum rate of pressure drop (−dp/dtmin) were measured to evaluate the myocardial protection effects of STV-1Na. The groups were compared with one-way analysis of variance (ANOVA) test. A value of p 0.05 between NL group and T group. But the serum cTnI level at 24 h after MI decreased in T group (22.7±5.3 ng/ml, p<0.05) compared with NL group (42.3±5.4 ng/ml). The serum cTnI level at 24 h in NL group and T group was significantly increased compared with S group (1.59±1.42 ng/ml) (p<0.01). Trimetazidine (0.248±0.021, p<0.01) decreased significantly the myocardial infarction area compared with NL group (0.362±0.027). The infarction areas in NL group (0.362±0.027) and T group (0.248±0.021) increased significantly compared with S group (0.072±0.1445) (p<0.01). In 1 week after MI, the +dp/dtmax in T group (7535±265) was not significantly different (p>0.05) compared with NL group (6702±329), and the -dp/dtmin in T group (−5511±400) was no significant difference (p>0.05) compared with NL group (−5400±339). In 2 weeks after MI, the +dp/dtmax in T group (8101±313) increased significantly compared with NL group (5868±412) (p<0.01), and the −dp/dtmin in T group (−6514±493) decreased significantly compared with NL group (−4750±463) (p<0.05). In 4 weeks after MI, in T group (7629±374) the +dp/dt max increased significantly compared with NL group (5876±200) (p<0.01,), and the −dp/dtmin in T group (−5883±436) decreased significantly compared with NL group (−4546±279) (p<0.05). The -dp/dt max in T group and NL group were significantly decreased (p<0.05) compared with S group in 1 week, 2 weeks and 4 weeks after the operation. The+dp/dtmin in T group and NL group were increased (p<0.05) compared to S group in 1 week, 2 weeks and 4 weeks after the operation. Conclusions Trimetazidine has myocardial protection effects on myocardial infarction and improves myocardial systolic and diastolic function in SD rats with acute myocardial infarction.

The association between plasma homocysteine and ambulatory blood pressure variability in patients with untreated hypertension

BACKGROUND Both homocysteine (Hcy) and blood pressure variability (BPV) are independent predictors of stroke, however, their relationship is rarely evaluated before. This study aimed to investigate the association Hcy and ambulatory BPV in subjects with untreated primary hypertension. METHODS A total of 252 eligible patients were recruited. Plasma Hcy was measured and 24-h ambulatory blood pressure monitoring was performed for each subject. The systolic and diastolic BPV values were calculated as the SD of individual blood pressure values during 24h, daytime and nighttime, and then stratified by the tertiles of Hcy concentration (T1 to T3). Univariate and multivariate linear regression models were used to assess the relationships between Hcy tertiles and BPV variables. RESULTS The mean values of Hcy from T1 to T3 were 7.51±1.21μmol/l, 11.09±1.07μmol/l and 19.14±6.26μmol/l, respectively. Systolic and diastolic mean blood pressures were similar among subjects with different Hcy tertiles. However, both systolic and diastolic BPV variables, no matter in 24-h, daytime or nighttime, were increasing significantly along with the rises in Hcy tertiles (all p<0.05 for linear trends analysis). Multivariate linear regression analysis indicated that Hcy tertiles were significantly associated with BPV variables, independently of mean blood pressures other confounding factors. In subgroup analysis, the associations between Hcy tertiles and BPV variables were enhanced by the increased risk stratification of hypertension. CONCLUSIONS Plasma Hcy was positively and independently associated with ambulatory BPV in patients with untreated hypertension.

Immunogenicity and Safety of a Chemically Synthesized Divalent Group A Streptococcal Vaccine

Background Group A streptococcus (GAS) infections and poststreptococcal sequelae remain a health problem worldwide, which necessitates searching for an effective vaccine, while no licensed GAS vaccine is available. We have developed a divalent peptide vaccine composed of 84 amino acids to cover the main GAS serotypes (M1 and M12 streptococci) in China, and herein, we aimed to evaluate immunogenicity and safety of this vaccine. Methods Mice were immunized with the vaccine. ELISA, indirect bactericidal test, and immunofluorescent assay were used to study immunogenicity. GAS challenge assay was used to test the protective effect. Safety was tested by histopathological analysis. Results Immunized group mice (n=16) developed higher titer antibody after immunization than nonimmunized group mice (n=16) did. This antibody can deposit on the surface of GAS and promote killing of GAS, resulting in 93.1% decrease of M1 GAS and 89.5% of M12 GAS. When challenged with M1 and M12 streptococci, immunized group mice had a higher survival rate (87.5% and 75%) than nonimmunized group mice (37.5% and 25%). No autoimmune reactions were detected on organs of mice. Conclusion The results suggest that this vaccine shows fair immunogenicity and safety, which will lead our research on GAS vaccine into clinical trial.

Critical appraisal of international guidelines on chronic heart failure: Can China AGREE?

Patients with chronic heart failure (CHF) have been evolving given the complex nature of the disease and the increasing number of patients, and themanagement of CHF challenges thewhole health systems globally [1,2]. The high burden of disease and the costs associated with hospitalization adversely affect individuals, families, and society [2]. The use of evidence-based clinical guidelines is an essential component of chronic disease management [3]. As a consequence, over the past decade, several national and international organizations have published clinical practice guidelines (CPGs) for the care of patients with CHF to enable clinicians to make appropriate treatment decisions [4]. There were more than 20 CPGs referred to manage CHF and developed over the last two decades. Many of these guidelines are purported to be evidence based, but there are differences in their recommendations and the nature and quality of the scientific evidence on which they are based. Several methodologies have been developed for the critical assessment of the quality of clinical guidelines [5]. Vlayen et al. conducted a systematic review of tools to appraise clinical practice guidelines [6]. They assessed 24 instruments from eight different countries developed between 1992 and 2003 and concluded that the highest quality instrument overall is the Appraisal of Guidelines for Research