Diagnostic performance of cardiac magnetic resonance for the detection of acute cardiac allograft rejection: a systematic review and meta-analysis

Background

Several studies have addressed the diagnostic accuracy of cardiac magnetic resonance (CMR) to assess acute cardiac allograft rejection (ACAR) compared with endomyocardial biopsy (EMB). But the methodological heterogeneity limited the clinical application of CMR. Accordingly, we have sought a comprehensive, systematic literature review and meta-analysis for the purpose.

Methods

Studies prior to September 1, 2014 identified by Medline/PubMed, EMBASE and Cochrance search and citation tracking were examined by two independent reviewers. A study was included if a CMR was used as a diagnostic test for the detection of ACAR.

Results

Of the seven articles met the inclusion criteria. Only four studies using T2 relaxation time as a CMR parameter could be pooled results, because the number of studies using other parameters was less than three. By using DerSimonian-Laird random effects model, meta-analysis demonstrated a pooled sensitivity of 90% [95% confidence interval (CI), 79% to 97%], a pooled specificity of 83% (95% CI, 78% to 88%), and a pooled diagnostic odds ratio (DOR) of 61.66 (95% CI, 18.09 to 210.10).

Conclusions

CMR seems to have a high sensitivity and moderate specificity in the diagnosis of ACAR. However, as a result of CMR for diagnostic ACAR should be comprehensively considered by physicians and imaging experts in the context of clinical presentations and imaging feature. Further investigations are still required to test different parameters and study condition.     

Cyst carcinoembryonic antigen in differentiating pancreatic cysts: A meta-analysis

Background

Using carcinoembryonic antigen in discriminating between benign and malignant disease remains controversial.

Aims

We aim to evaluate the diagnostic accuracy of cyst fluid carcinoembryonic antigen in predicting malignant pancreatic cystic lesions.

Methods

We performed a literature search of MEDLINE and EMBASE. We included studies that compared the diagnostic accuracy of carcinoembryonic antigen with histology. Pooled estimates of diagnostic precision were calculated using random-effects models.

Results

Eight studies (504 patients) were included. The carcinoembryonic antigen cutoff level for determining a malignant cyst ranged from 109.9 to 6000 ng/mL. Pooled estimates of carcinoembryonic antigen in malignant cysts prediction were poor: pooled sensitivity of 63%, pooled specificity of 63%. The positive likelihood ratio was 1.89 and the negative likelihood ratio was 0.62. The diagnostic odds ratio was 3.84. The area under the summary receiver–operating characteristic curve was 0.70. In subgroup analysis of patients with mucinous cysts (mucinous cystic neoplasm and intraductal papillary mucinous neoplasm; 5 studies, 227 patients), pooled sensitivity was 65%, pooled specificity 66% and diagnostic odds ratio 4.74 respectively.

Conclusion

This meta-analysis suggests that the accuracy of carcinoembryonic antigen in differentiating “between benign and malignant” pancreatic cysts was poor. The decision to perform surgical resection for pancreatic cystic lesions should not be based solely on carcinoembryonic antigen level.     

Diagnostic Value of Ankle-Brachial Index in Peripheral Arterial Disease: A Meta-analysis

Background

In a previous review, we reported that ankle brachial index (ABI) ≤ 0.90 could reliably identify patients with peripheral artery disease (PAD). Since then, more studies have been published which may extend the power of a meta-analysis of studies of diagnostic accuracy of the ABI. MEDLINE and several other databases were searched for studies on sensitivity and specificity of using ABI ≤ 0.90 for PAD diagnosis compared with angiography.

Methods

Quality of each study was assessed by standards for reporting diagnostic accuracy initiative and quality assessment for studies of diagnostic accuracy tool. Heterogeneity was assessed using the Cochran Q statistic, χ², and inconsistency index. The area under the curve and Q* were estimated using summary receiver operator curve. The pooled diagnostic odds ratio (DOR), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of ABI ≤ 0.90 to diagnose PAD were estimated using Meta-DiSc software (Meta-DiSc, Madrid, Spain).

Results

Four studies comprising 569 patients (922 limbs) met inclusion criteria. Significant heterogeneity among these studies was not detected in DOR but was evident in pooled sensitivity, specificity, PLR, and NLR. The area under the curve under the summary receiver operator curve is 0.87 (standard error = 0.02) and diagnostic accuracy (Q*) is 0.80 (standard error = 0.02). Additionally, DOR was 15.33 with corresponding 95% confidence intervals of 9.39-25.02. The pooled sensitivity and specificity of ABI ≤ 0.90 for PAD diagnosis were 75% and 86% and the pooled PLR and NLR were 4.18 and 0.29, respectively.

Conclusions

We conclude that test of ABI ≤ 0.90 can be a useful tool to identify PAD with serious stenosis in clinical practice.     

Head-up tilt testing for diagnosing vasovagal syncope: A meta-analysis

Background

A systematic evaluation focused on sensitivity and specificity of head-up tilt testing (HUT) for diagnosing vasovagal syncope has not been previously performed. We conducted a meta-analysis of studies comparing HUT outcome between patients with syncope of unknown origin and control subjects without previous syncope.

Methods

We searched Pubmed and Embase databases for all English-only articles concerning case-control studies estimating the diagnostic yield of HUT, and selected 55 articles, published before March 2012, including 4361 patients and 1791 controls. The influence of age, test duration, tilt angle, and nitroglycerine or isoproterenol stimulation on tilt testing outcome was analyzed.

Results

Head-up tilt testing demonstrated to have a good overall ability to discriminate between symptomatic patients and asymptomatic controls with an area under the summary receiver-operating characteristics curve of 0.84 and an adjusted diagnostic odds ratio of 12.15 (p < 0.001). A significant inverse relationship between sensitivity and specificity of tilt testing for each study was observed (p < 0.001). At multivariate analysis, advancing age and a 60° tilt angle showed a significant effect in reducing sensitivity and increasing specificity of the test. Nitroglycerine significantly raised tilt testing sensitivity by maintaining a similar specificity in comparison to isoproterenol.

Conclusions

The results from this meta-analysis show the high overall performance of HUT for diagnosing vasovagal syncope. Our findings provide useful information for evaluating clinical and instrumental parameters together with pharmacological stressors influencing HUT accuracy. This could allow the drawing of tilt testing protocols tailored on the diagnostic needs of each patient with unexplained syncope.     

Diagnostic accuracy of glycated hemoglobin compared with oral glucose tolerance test for diagnosing diabetes mellitus in Chinese adults: A meta-analysis

Aims

A meta-analysis was conducted to evaluate the diagnostic value of glycated hemoglobin (HbA1c) ≥6.5% (48 mmol/mol) for diabetes in Chinese adults.

Methods

Oral glucose tolerance test (OGTT) was selected as the reference standard. PubMed, EMBASE, CNKI, Wanfang Data, and VIP were searched to obtain all diagnostic tests with HbA1c ≥6.5% (48 mmol/mol) for diabetes in Chinese adults published between January 2003 and October 2013. The qualities of the included studies were assessed by using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Meta-DiSc software was used to conduct a comprehensive quantitative assessment, and summary receiver operating characteristic (sROC) curves were obtained.

Results

A total of 9 studies with 25,932 subjects were included. Pooled sensitivity was 0.518, pooled specificity 0.956, pooled positive likelihood ratio 19.007 and pooled negative likelihood ratio was 0.477. Pooled diagnostic odds ratio was 40.631. AUC_sROC was 0.929.

Conclusion

Compared with OGTT, using HbA1c ≥6.5% (48 mmol/mol) to diagnose diabetes in Chinese adults exhibited high specificity and low sensitivity and would have failed to diagnose 48.7% of newly diagnosed diabetes. The diagnostic HbA1c value could be reduced to improve sensitivity. Long-term prospective studies are required to establish an appropriate HbA1c value as a diagnostic criterion for diabetes in China.     

Meta-analysis of stroke after transradial versus transfemoral artery catheterization

Background

Transradial (TR) catheterization is gaining popularity due to its association with lower bleeding and access site complications, improved patient comfort, and lower costs compared to transfemoral (TF) catheterization; however, there is concern that TR catheterization may be associated with an increased risk of neurological complications. New randomized data has emerged since the publication of the last meta-analysis evaluating the risk of stroke between TR and TF catheterization in 2009.

Methods

We conducted a meta-analysis of randomized studies published until 2013 reporting risk of stroke in TR vs. TF catheterization.

Results

Data from 11,273 patients in 13 studies were collated. The majority of patients were men, and 8987 (79.7%) were enrolled in acute coronary syndrome trials. Very few patients had a history of prior coronary artery bypass grafting, and approximately 2/3 of patients underwent percutaneous coronary intervention. Stroke occurred in 25 of 5659 patients in the TR group, vs. 24 of 5614 patients in the TF group. There was no difference in stroke rates between the TR and TF groups (risk difference 0.00%, 95% confidence interval − 0.29%–0.25%, p = 0.88).

Conclusions

TR catheterization is not associated with a significant increase in stroke compared to TF catheterization.     

Cardiac magnetic resonance myocardial perfusion imaging for detection of functionally significant obstructive coronary artery disease: A prospective study

Background

Cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI) is considered a state of the art non-invasive modality for the detection of reversible ischemia. Recent studies have shown its utility in the diagnosis of coronary artery disease (CAD) and superiority over other established techniques. However, only a few studies compared CMR-MPI against the invasive standard including fractional flow reserve (FFR) and clinical validation in non-specialized centers is scarce. The aim of this study was to validate CMR-MPI in a real-world clinical environment and to test its diagnostic accuracy in symptomatic patients with suspected CAD versus FFR as the reference standard of functionally significant disease.

Methods and results

103 symptomatic consecutive patients (62 ± 8.0 years, 66% males) with suspected CAD and intermediate or high probability of disease underwent sequential CMR and invasive coronary angiography (XA). The CMR protocol included stress-rest adenosine perfusion, SSFP cine imaging and late-enhancement imaging. Functionally significant CAD was defined as occlusive/sub-occlusive stenoses on XA or non-occlusive stenoses with a FFR measurement of < 0.80 in vessels > 2 mm. On a patient-based model, CMR-MPI had sensitivity, specificity, positive and negative predictive values of 89%, 88%, 85%, and 91%, respectively, with a global accuracy of 88%. On a vessel-based analysis, these values were 80%, 93%, 79% and 94%, respectively, with a global accuracy of 90%.

Conclusions

CMR-MPI had a very high accuracy for detection of functionally significant CAD as assessed by FFR in patients with intermediate to high pretest probability.     

Prognostic value of adenosine stress perfusion cardiac MRI with late gadolinium enhancement in an intermediate cardiovascular risk population

Background

The high diagnostic accuracy of adenosine stress cardiac magnetic resonance (AS-CMR) for detecting coronary artery stenoses, with high sensitivity and specificity, is well documented. Prognostic data, particularly in non-low risk study populations and for greater than 12 months of follow up, is however lacking or variable in its findings. We present prognostic data, in an intermediate cardiovascular risk cohort undergoing adenosine stress perfusion CMR, over approximately 2 years of follow up.

Methods

The study population comprised 362 patients referred for a clinically indicated stress CMR and included patients with proven coronary artery disease (CAD; n = 157) or unknown CAD status, yet an intermediate cardiovascular risk profile (n = 205). Perfusion imaging was performed at stress (adenosine 140 μg/kg/min) and rest on a 1.5 T system. Patient records and state-wide hospital databases were reviewed. Major adverse cardiac events — death, myocardial infarction, revascularisation or ischaemic hospitalisation — were evaluated over a median follow up of 22 months.

Results

Of the 362 cases, 90 had a stress perfusion CMR positive for ischaemia and experienced a MACE rate of 24%. Of the 272 negative CMR scans, 225 were also negative for late gadolinium enhancement, and in this group MACE was encountered in only 6 (2.7%) patients. Accordingly a negative stress CMR afforded a freedom from MACE of 97.3%. Freedom from death/myocardial infarction was 99.6%.

Conclusions

In patients with confirmed coronary artery disease or at intermediate risk for cardiovascular events, a negative stress perfusion CMR is associated with an excellent prognosis over nearly 2 years of follow up.     

Impact of new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy

Background

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that can lead to sudden cardiac death. The diagnostic criterion has recently been revised and through the use of cardiac magnetic resonance (CMR) imaging this study aimed to assess the clinical impact of comparing the original 1994 task force (TF) criterion to the revised 2010 criterion.

Methods

We evaluated 173 consecutive CMR scans of patients referred with clinical suspicion of ARVC between 2008 and 2011. We then compared the prevalence of major and minor CMR criteria by applying the two criteria.

Results

Using the 1994 TF criterion, 13 (7.5%) patients had definite, 11 (6.4%) had borderline, and 39 (22.5%) had possible ARVC. Using the 2010 TF criterion, 10 (5.8%) patients had definite, 1 had borderline, and 7 had (0.04%) possible ARVC. With the 1994 criterion, 81 patients satisfied CMR criterion, of which 36 (44%) had major and 45 (56%) had minor criteria. Upon reclassification with the revised criterion, 61 of the 81 patients were not assigned any criteria, even though many patients had significant risk factors. The negative predictive values (NPV) for both CMR criteria were 100% but the positive predictive values (PPV) for combined CMR major or minor criteria improved from 23% to 55%.

Conclusions

Revision of the criterion has enhanced the diagnostic capabilities of CMR but has resulted in a large cohort of patients not classified. In these patients, there is presently no official consensus on imaging or clinical strategy for surveillance of the evolution of pathology over time.     

Diagnostic accuracy of serological diagnosis of hepatitis C and B using dried blood spot samples (DBS): two systematic reviews and meta-analyses

Background

Dried blood spots (DBS) are a convenient tool to enable diagnostic testing for viral diseases due to transport, handling and logistical advantages over conventional venous blood sampling. A better understanding of the performance of serological testing for hepatitis C (HCV) and hepatitis B virus (HBV) from DBS is important to enable more widespread use of this sampling approach in resource limited settings, and to inform the 2017 World Health Organization (WHO) guidance on testing for HBV/HCV.

Methods

We conducted two systematic reviews and meta-analyses on the diagnostic accuracy of HCV antibody (HCV-Ab) and HBV surface antigen (HBsAg) from DBS samples compared to venous blood samples. MEDLINE, EMBASE, Global Health and Cochrane library were searched for studies that assessed diagnostic accuracy with DBS and agreement between DBS and venous sampling. Heterogeneity of results was assessed and where possible a pooled analysis of sensitivity and specificity was performed using a bivariate analysis with maximum likelihood estimate and 95% confidence intervals (95%CI). We conducted a narrative review on the impact of varying storage conditions or limits of detection in subsets of samples. The QUADAS-2 tool was used to assess risk of bias.

Results

For the diagnostic accuracy of HBsAg from DBS compared to venous blood, 19 studies were included in a quantitative meta-analysis, and 23 in a narrative review. Pooled sensitivity and specificity were 98% (95%CI:95%–99%) and 100% (95%CI:99–100%), respectively. For the diagnostic accuracy of HCV-Ab from DBS, 19 studies were included in a pooled quantitative meta-analysis, and 23 studies were included in a narrative review. Pooled estimates of sensitivity and specificity were 98% (CI95%:95–99) and 99% (CI95%:98–100), respectively. Overall quality of studies and heterogeneity were rated as moderate in both systematic reviews.

Conclusion

HCV-Ab and HBsAg testing using DBS compared to venous blood sampling was associated with excellent diagnostic accuracy. However, generalizability is limited as no uniform protocol was applied and most studies did not use fresh samples. Future studies on diagnostic accuracy should include an assessment of impact of environmental conditions common in low resource field settings. Manufacturers also need to formally validate their assays for DBS for use with their commercial assays.

     

Indications,safety and image quality of cardiovascular magnetic resonance: Experience in > 5,000 North American patients

Background

CMR offers accurate assessment of structure and function with high resolution. Although the use of CMR has been well established in Europe, information is lacking for the extent of this emerging modality in North America.

Objectives

This study aimed to summarize indications, safety, image quality, extent of contrast use and extent of stress tests performed in a high-volume CMR centre.

Methods

Consecutive patients scanned from July 2005 to November 2010 were included, with duplicates and research subjects removed. Original clinical referrals were categorized into 10 main indications.

Results

Retrospective analysis was performed on 6463 patients (mean ± SD age = 50 ± 17). The most common clinical indications were non-ischemic cardiomyopathies (28%), including myocarditis (18%), coronary artery disease (17%), ARVD and/or other RV disease (12%), and congenital heart disease (11%). Gadolinium-based contrast was given to 89.5% of patients as part of their CMR protocol. Of 10.9% (703/6463) of patients that underwent stress CMR, adenosine was administered most commonly. Of 703 patients, 1 (0.14%) suffered ventricular tachycardia during adenosine stress, and transient, asymptomatic AV block was occasionally observed. Moderate to severe complications after contrast agent administration occurred in 9 (0.16%) of 5782 contrast-enhanced studies, characterized by nausea and vomiting in 6 (0.12%) and by symptoms of acute systemic allergic reaction in 2 (0.04%). Image quality was good (82.0%), moderate but diagnostic (16.6%) and poor in 1.4% of cases.

Conclusion

In the high-volume CMR centre, main clinical indications were for myocarditis/cardiomyopathies, coronary artery disease and RV-related queries. CMR showed an excellent safety profile and high image quality in 99% of cases.     

Risk of Bleeding on Triple Antithrombotic Therapy After Percutaneous Coronary Intervention/Stenting: A Systematic Review and Meta-analysis

Background

There are no reported randomized controlled trials of triple antithrombotic therapy (TT; aspirin plus a thienopyridine plus vitamin K antagonist) vs dual antiplatelet therapy (DAPT; aspirin plus a thienopyridine) among patients undergoing percutaneous coronary intervention with stenting (PCI-S). A systematic review and meta-analysis was undertaken to assess the risk of bleeding among patients receiving TT after PCI-S.

Methods

Electronic databases were searched for studies reporting bleeding among patients receiving TT after PCI-S. Of the 4108 articles screened, 18 met study inclusion criteria and underwent detailed data extraction: of these, 6 reported in-hospital outcomes, 14 reported 30-day outcomes, and 9 reported 6-month outcomes. At each time point, pooled estimates of bleeding with TT were ascertained and where possible summary odds ratios (ORs) for comparative risks vs DAPT were calculated.

Results

The pooled estimate of major bleeding rate with TT post PCI-S was 2.38% by 30 days postprocedure (95% confidence interval [CI], 0.98-3.77%) and 4.55% by 6 months postdischarge (95% CI, 0.56-8.53%). At 30 days and 6 months the rates of major bleeding with TT were significantly higher than those observed with DAPT: OR, 2.38 at 30 days (95% CI, 1.05-5.38) and OR, 2.87 at 6 months (95% CI, 1.47-5.62).

Conclusions

This systematic review and meta-analysis of reports of triple therapy with a vitamin K antagonist, aspirin, and clopidogrel after PCI-S provides precise and valid bleeding risk data. Based on existing observational studies the rates of major and any bleeding associated with TT are clinically important and significantly greater than those reported with DAPT.     

The emerging role of cardiac computed tomography for the assessment of coronary perfusion: a systematic review and meta-analysis

Background

Computed tomography perfusion (CTP) is an emerging method which, coupled with the anatomical detail afforded by cardiac computed tomographic angiography (CCTA), may allow for determination of both structural and physiologic significance of coronary stenoses with a single imaging modality. This study was designed to execute a systematic review/meta-analysis to determine the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CTP as compared with reference standards for detection of significant coronary artery stenoses and impaired perfusion.

Methods

A systematic review identified 13 out of 4368 studies allowing a calculation of sensitivity, specificity, PPV, and NPV on a per patient or per vessel or per segment basis using radionuclide myocardial perfusion imaging (MPI), conventional coronary angiography (CCA), magnetic resonance perfusion imaging (MRPI), or fractional flow reserve (FFR) as the reference standard. Meta-analyses of results were carried out using random effects modelling.

Results

Most studies used a maximal vasodilator stress protocol with adenosine, provided information mainly on a per vessel basis, and used myocardial perfusion imaging or CCA as the reference standard. Of the studies comparing combinations of both anatomical and functional imaging, the most rigourous standard was CCA/FFR. Compared with the latter, CCTA/CTP had sensitivity, specificity, PPV, and NPV of 81%, 93%, 87%, and 88%, respectively.

Conclusions

CTP shows promise as an adjunct to CCTA, potentially allowing determination of both structural and physiologic significance with a single imaging modality.     

Right atrial volume and phasic function in pulmonary hypertension

Background

Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH.

Methods

We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR.

Results

Maximum RA volume index was significantly higher in PH patients (56 [44–70] ml/m²) than in controls (40 [30–48] ml/m²) (p < 0.001). Reservoir volume index was significantly lower in PH than in controls (p < 0.001), but conduit volume index was higher in PH than in controls (p = 0.008). RA EF was similar when comparing the two groups (p = 0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p < 0.001) but was reduced in advanced PH patients with WHO functional class IV (p < 0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance.

Conclusions

PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH.     

Screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension: A systematic review

Objective

Pulmonary arterial hypertension (PAH) is a frequent complication in connective tissue diseases (CTD), especially in systemic sclerosis (SSc), and is associated with a high degree of morbidity and mortality. We undertook a systematic review for the screening tests for CTD-PAH.

Methods

A systematic literature search of PAH in CTD was performed in available databases through June 2012. Our evaluation of diagnostic tests was focused on patients with PAH confirmed by right heart catheterization (RHC).

Results

The search resulted in 2805 titles and 838 abstracts. Our final inclusion encompassed 22 articles—six of which were case–control studies and 16 were cohort studies. Twelve studies assessed the tricuspid regurgitation velocity (VTR) or equivalent right ventricular systolic pressure (RVSP) using transthoracic echocardiogram (TTE) as a threshold for RHC in patients suspected as having PAH. The screening threshold for RHC was VTR from >2.73 to >3.16 m/s without symptoms or 2.5–3.0 m/s with symptoms and resulted in 20–67% of patients having RHC-proven PAH. Three studies looked at pulmonary function tests and found that a low lung diffusing capacity for carbon monoxide (DLCO) (45–70% of predicted) is associated with a 5.6–7.4% development of PAH, and a decline in DLCO% is associated with an increase in the specificity (for DLCO ≤60%, spec = 45%; and for DLCO ≤50%, spec = 90%) for PAH. Five studies assessed N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), where a cutoff >239 pg/ml had a sensitivity of 90–100%.

Conclusions

Our systematic review revealed that most evidence exists for TTE, pulmonary function tests, and NT-ProBNP for screening and diagnosis of SSc-PAH; however, more robust studies are needed.     

Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: A systematic review and meta-analysis

Background

Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis.

Design and Methods

We searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association.

Results

Eleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR _{DD versus II} = 1.81, 95% CI 1.23–2.66, P = 0.003; OR _{ID versus II} = 1.50, 95% CI 1.25–1.80, P < 0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed.

Conclusion

Meta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.     

Meta-analysis of the diagnostic yield and safety of electromagnetic navigation bronchoscopy for lung nodules

Objective

This meta-analysis is to evaluate the overall diagnostic yield and accuracy of electromagnetic navigation bronchoscopy (ENB)-based targeted biopsies in detecting peripheral lesions.

Methods

A systematic search in PubMed was performed using “electromagnetic navigation bronchoscopy” crossed with “peripheral lesions” and “lung nodules”. Test performance characteristics with the use of forest plots, summary receiver operating characteristic curves (SROCs) and bivariate random effects were summarized using Meta-Disc software. Adverse events and complications were recorded if reported.

Results

A total of 17 studies (1,106 patients with peripheral lung lesions) were included in this analysis. The pooled sensitivity, specificity, positive likelihood ratios (PLRs), negative likelihood ratios (NLRs), and diagnostic odds ratios (DORs) of ENB was 82%, 100%, 19.36, 0.23, and 97.62, respectively. The area under the curve (AUC) for the SROC was 0.9786. No procedure-related complication was found.

Conclusions

ENB is an effective and safe procedure in diagnosing peripheral lung lesions.     

Diagnostic accuracy of a clinical prediction rule (CPR) for identifying patients with recent-onset undifferentiated arthritis who are at a high risk of developing rheumatoid arthritis: A systematic review and meta-analysis

Objectives

The Leiden clinical prediction rule (CPR) was developed in 2007 to predict disease progression in patients with recent-onset undifferentiated arthritis (UA). This systematic review and meta-analysis investigates the predictive ability of the rule at identifying patients who are at a high risk of developing rheumatoid arthritis (RA).

Methods

A systematic review of the literature search was conducted from 2007 to May 2013 to identify studies that validated the rule. This study adhered to the PRISMA guidelines. The methodological quality of studies was assessed using the QUADAS-2 tool. Pooled sensitivity and specificity values for each of the cut points were generated using a bivariate random-effects model. Heterogeneity was assessed using the variance of logit-transformed sensitivity and specificity. Bayes' theorem was used to calculate post-test probability of progression from UA to RA.

Results

The search identified four relevant studies, resulting in six data sets (n = 1084). A cut point of ≥9 was identified as the optimal cut point for determining progression to RA. It is associated with a greater pooled specificity (0.99, 95% CI 0.95–1.00) than sensitivity (0.31, 95% CI 0.24–0.37). Using Bayes' theorem, a score of ≥9 points increased the pre-test probability from 40.04% to 93.63%. A less stringent cut-off of ≥8 also identified a significant proportion of patients at risk of RA who have a high likelihood of progressing to RA (LR + 9.5, 95% CI 6.21–14.54).

Conclusion

A cut point of ≥9 offers an optimal estimate for identifying patients with UA who are at a high risk of developing RA and warrant intervention. However, a number of methodological limitations identified across studies suggest that the results should be interpreted cautiously and that further validation of the Leiden CPR is necessary.     

Where and how to inject the knee—A systematic review

Objectives

The knee can be injected at different anatomic sites with or without image-guidance. We undertook a systematic review to determine the accuracy of intra-articular knee injection (IAKI) and whether this varied by site, use of image-guidance, and experience of injectors, and whether accuracy of injection, site, or use of image-guidance influenced outcomes following IAKIs.

Methods

Medline, Embase, AMED, CINAHL, Web of Knowledge, Cochrane Central Registers for Controlled Trials up to Dec 2012 were searched for studies that evaluated either accuracy of IAKIs or outcomes related to accuracy, knee injection sites, or use of image-guidance. Within-study and between-study analyses were performed.

Results

Data from 23 publications were included. Within-study analyses suggested IAKIs at the superomedial patellar, medial midpatellar (MMP), superolateral patellar (SLP) and lateral suprapatellar bursae sites were more accurate when using image-guidance than when blinded (ranges of pooled risk difference 0.09–0.19). Pooling data across studies suggested blinded IAKIs at the SLP site were most accurate (87%) while MMP (64%) and anterolateral joint line (ALJL) sites were (70%) least accurate. Overall about one in five blinded IAKIs were inaccurate. There was some evidence that experience of the injector was linked with improved accuracy for blinded though not image-guided injections. Based on a small number of studies, short but not longer-term outcomes for ultrasound-guided were found to be superior to blinded IAKIs.

Conclusions

Image-guided IAKIs are modestly more accurate than blinded IAKIs especially at the MMP and ALJL sites. Blinded injections at SLP site had good accuracy especially if performed by experienced injectors. Further studies are required to address the question whether accurate localization is linked with an improved response.     

Association Between rs2200733 and rs7193343 Genetic Variants and Atrial Fibrillation in a Spanish Population,and Meta-analysis of Previous Studies

Introduction and objectives

The objectives of this study were to analyze the association between two genetic variants (rs2200733 and rs7193343) in a Spanish population and the risk of developing atrial fibrillation, and to carry out a systematic review and meta-analysis of these associations.

Methods

We performed a case-control study involving 257 case patients with atrial fibrillation and 379 controls. The case patients were individuals who had donated samples to the Spanish National DNA Bank; the controls were participating in a population-based cross-sectional study. Genotyping was carried out using a TaqMan assay. We conducted a systematic literature search in which 2 independent reviewers extracted the necessary information. The study involved a meta-analysis, a heterogeneity analysis, and a meta-regression analysis to identify the variables that explain the heterogeneity across studies.

Results

In our population, the presence of atrial fibrillation was found to be associated with rs2200733 (odds ratio = 1.87; 95% confidence interval, 1.30-2.70), but not with rs7193343 (odds ratio = 1.18; 95% confidence interval, 0.80-1.73). In the meta-analysis, we observed an association between atrial fibrillation and both variants: odds ratio = 1.71 (95% confidence interval, 1.54-1.90) for rs2200733 and odds ratio = 1.18 (95% confidence interval, 1.11-1.25) for rs7193343. We observed heterogeneity among the studies dealing with the association between rs2200733 and atrial fibrillation, partially related to the study design, and the strength of association was greater in case-control studies (odds ratio = 1.83) than in cohort studies (odds ratio = 1.41).

Conclusions

Variants rs2200733 and rs7193343 are associated with a higher risk of atrial fibrillation. Case-control studies tend to overestimate the strength of association between these genetic variants and atrial fibrillation.