[Show abstract][Hide abstract] ABSTRACT: A wide array of drugs are available for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), but the evidence for the comparative effectiveness is controversial.The objective of this study is to evaluate the comparative effectiveness and safety of monodrug therapies for BPH.Data sources are MEDLINE, EMBASE, and the Cochrane Library.We included randomized controlled trials that compared α-blockers, 5-alpha reductase inhibitors (5ARIs), muscarinic receptor antagonists (MRAs), phosphodiesterase-5 inhibitor (PDE5-Is), or placebo for the treatment of BPH.Comparative effectiveness and safety were pooled by both traditional meta-analysis and network meta-analysis. Summary effect size was calculated as mean difference (MD) and relative risk (RR), together with the 95% confidence intervals (CIs).This study included 58,548 participants from 124 trials in total. When compared with placebo, α-blockers, 5ARIs, and PDE5-Is reduced International Prostate Symptom Score (IPSS) by -1.35 to -3.67 points and increased peak urinary flow rate (PUF) by -0.02 to 1.95 mL/s, with doxazosin (IPSS: MD, -3.67[-4.33 to -3.02]; PUF: MD, 1.95[1.61 to 2.30]) and terazosin (IPSS: MD, -3.37 [-4.24 to -2.50]; PUF: MD, 1.21[0.74 to 1.66]) showing the greatest improvement. The improvement in the IPSS was comparable among tamsulosin, alfuzosin, naftopidil, silodosin, dutasteride, sildenafil, vardenafil, and tadalafil. The incidence of total adverse events and withdraws due to adverse events were generally comparable among various agents.In conclusion, α-blockers, 5ARIs, and PDE5-Is are effective for BPH, with doxazosin and terazosin appearing to be the most effective agents. Drug therapies for BPH are generally safe and well-tolerated, with no major difference regarding the overall safety profile.
Medicine 07/2015; 94(27):e974. DOI:10.1097/MD.0000000000000974 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We performed a meta-analysis to assess whether blood can be substituted for tumor tissue in K-ras mutation testing. PubMed, EMBASE, MEDLINE, and BIOSIS databases were searched. Twenty-three studies including 1261 patients were included. The pooled overall sensitivity, specificity, and concordance rate were 0.69 (95% CI: 0.59-0.78), 0.96 (95% CI: 0.93-0.97), and 0.86 (95% CI: 0.82-0.89), respectively. Subgroup analysis indicated that plasma (sensitivity: 0.74; mutation rate: 0.34) exhibited superior sensitivity compared with serum (sensitivity: 0.45; mutation rate: 0.24). We conclude that blood is a suitable substitute for tumor tissue in K-ras mutation testing. K-ras mutation positivity in blood can be used to identify patients who should not receive EGFR monoclonal antibody therapy, but the absence of blood positivity does not necessarily imply negativity.
[Show abstract][Hide abstract] ABSTRACT: Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated.
To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD.
We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions.
Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tong-xin-luo capsules for at least three months.
Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs).
Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea.
The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.
[Show abstract][Hide abstract] ABSTRACT: The effectiveness of phosphodiesterase type 5 inhibitors (PDE5-Is) for erectile dysfunction (ED) varies considerably among trials, but available studies investigating the factors that affect the effectiveness are few and findings are not consistent. A systematic search was performed in PubMed, Cochrane Library, and EMBASE to identify randomized controlled trials comparing PDE5-Is with placebo for the treatment of ED. The methodological quality of included studies was assessed by the Cochrane Collaboration's tool for assessing risk of bias. The associations between prespecified study-level factors and effectiveness were tested by a random effects meta-regression model. This study included 93 trials with 26 139 patients. When all PDE5-Is were grouped together, Caucasian ethnicity was associated with 15.636% (95% confidence interval [CI]: 0.858% to 32.579%) increase in risk ratio (RR) for Global Assessment Questionnaire question-1 (GAQ-1), and 1.473 (95% CI: 0.406 to 2.338) score increase in mean difference (MD) for posttreatment International Index of Erectile Function-Erectile Function domain score (IIEF-EF), compared to Asian ethnicity. A one-score increase in baseline IIEF-EF was associated with -5.635% (95% CI: -9.120% to -2.017%) reduction in RR for GAQ-1, and -0.229 (95% CI: -0.425 to -0.042) score decrease in MD for posttreatment IIEF-EF. In conclusion, PDE5-Is are more effective in Caucasians than Asians, and in patients with more severe ED.
Asian Journal of Andrology 05/2015; DOI:10.4103/1008-682X.154304 · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor (EGFR) mutations to guide EGFR tyrosine kinase inhibitors (TKIs) treatment of patients with nonsmall cell lung cancer (NSCLC).We conducted this systematic review and meta-analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations.MEDLINE, EMBASE, and the Cochrane Library were searched for studies that provided data to estimate the accuracy of blood testing against tissue testing in NSCLC patients and/or those directly compared the efficacy of EGFR TKIs in EGFR mutant and wild-type patients according to sources of specimens.Sensitivity, specificity, and concordance rate were used as measures of the accuracy. Risk ratio (RR) for objective response and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were used as measures for treatment efficacy. We combined the effects by using the fixed-effects model unless there was evidence of heterogeneity, in which case a random-effects mode was used.This systematic review included 25 studies with 2605 patients. The pooled overall sensitivity, specificity, and concordance rate were 0.61, 0.90, and 0.79, respectively. Serum showed lower sensitivity (0.56 vs 0.65) but higher specificity (0.95 vs 0.85) and higher concordance (0.86 vs 0.74) than plasma. EGFR mutations (exon 19 or 21) in blood were significantly associated with objective response (RR: 4.08; 95% confidence interval [CI] 2.48-6.70), PFS (HR: 0.72; 95% CI 0.64-0.80), and OS (HR: 0.71; 95% CI 0.50-0.99). Importantly, the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma.Blood, in particular serum, is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the absence of blood positivity should not necessarily be construed with confirmed negativity.
Medicine 05/2015; 94(21):e775. DOI:10.1097/MD.0000000000000775 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current data on the concordance of KRAS, BRAF, PIK3CA mutation status or PTEN expression status between primary tumors and metastases in colorectal cancer (CRC) are conflicting. We conducted a systematic review and meta-analysis to examine concordance and discordance of the status of these four biomarkers between primary tumors and corresponding metastases in CRC patients. The biomarker status in primary tumors was used as the reference standard. Concordance data for KRAS, BRAF, PIK3CA and PTEN were provided by 43, 16, 9 and 7 studies, respectively. The pooled concordance rate was 92.0% (95% CI: 89.7%-93.9%) for KRAS, 96.8% (95% CI: 94.8%-98.0%) for BRAF, 93.9% (95% CI: 89.7%-96.5%) for PIK3CA and 71.7% (95% CI: 57.6%-82.5%) for PTEN. The pooled false positive and false negative rates for KRAS were 9.0% (95% CI: 6.5%-12.4%) and 11.3% (95% CI: 8.0%-15.8%), respectively. KRAS, BRAF and PIK3CA mutations are highly concordant between primary tumors and corresponding metastases in CRC, but PTEN loss is not. Nine percent of patients with wild-type KRAS in primary tumors who received anti-EGFR treatment had mutant KRAS in metastases, while 11.3% patients with mutant KRAS primary tumors had wild-type KRAS in the metastases. These 11.3% patients currently do not receive potentially beneficial anti-EGFR treatment.
[Show abstract][Hide abstract] ABSTRACT: The prognostic value of phosphorylated Akt (pAkt) overexpression in breast cancer has been investigated by many studies with inconsistent results. This systematic review was conducted to evaluate the association of pAkt overexpression with breast cancer prognosis in terms of overall survival and disease-free survival. Three electronic databases (PubMed, EMBASE and Chinese Biomedical Literature Database) were comprehensively searched. Hazard ratios (HRs) with 95% confidence intervals (CIs) from different studies were combined using the random-effects model. In total, 33 studies with 9,836 patients were included for final analysis. The summary HR for overall survival and disease-free survival was 1.52 (95% CI: 1.29-1.78) and 1.28 (95% CI: 1.13-1.45), respectively, indicating higher risk of death and disease recurrence associated with pAkt overexpression. The results were robust in sensitivity analyses by omitting one study each time and by using the fixed-effects model instead. Subgroup and meta-regression analyses did not show that the prognostic effect of pAkt overexpression would change materially with such factors as population, status of hormone receptors, hormonal or trastuzumab treatment given, analyzing method (univariate versus multivariate) and methodological quality of the original studies. In conclusion, the available evidence suggests that pAkt overexpression is an adverse prognostic factor for breast cancer.
[Show abstract][Hide abstract] ABSTRACT: A meta-analysis may provide more conclusive results than a single trial. The major cost of meta-analysis is the time of waiting before the meta-analysis becomes available and resources spent on consequent trials that may not be necessary. The objective of this study is to address how often the result of a single trial, in particular the first trial, differs from that of its corresponding meta-analysis so as to reduce unnecessary waiting time and subsequent trials.
A meta-epidemiologic study was conducted by collecting meta-analyses from the Cochrane Database of Systematic Reviews and five major medical journals. Effect size of a single trial was compared with that of its corresponding meta-analysis. The single trial includes the first trial, last trial and any trial randomly selected from the meta-analysis.
647 meta-analyses are included and the median number of trials in a meta-analysis is 5. 233 (36.0%) meta-analyses have the first trial with a statistically significant result. When the first trial is statistically significant, 84.1% (95% CI: 79.4%, 88.8%) of the corresponding meta-analyses is both in the same direction and statistically significant. When the first trial is statistically insignificant, 57.9% (95% CI: 53.2%, 62.8%) of the meta-analysis is also statistically insignificant regardless of direction. The median number of years is 6.5 years from the first to the 5th trial.
The conclusion of the first trial that the treatment is effective or harmful is mostly likely correct. A statistically significant trial agrees more often with its corresponding meta-analysis than a large trial. These findings imply that particularly in some urgent, life-saving or other critical circumstances for which no other effective methods are available, cautious recommendation based on the significant result of the first trial seems justifiable and could start use of an effective intervention by 5-8 years earlier.
PLoS ONE 12/2014; 9(12):e113994. DOI:10.1371/journal.pone.0113994 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In advanced non-small cell lung cancer (NSCLC), the effectiveness of standard cytotoxic chemotherapy seems to have reached a 'plateau', and there is a continuous need for new treatments to further improve the prognosis. Cetuximab is a monoclonal antibody targeted at the epidermal growth factor receptor (EGFR) signalling pathway. Basically, it is designed to inhibit the growth and metastasis among other biological processes of cancer. In combination with chemotherapy, it has been evaluated as a first-line treatment for advanced NSCLC in some randomised controlled trials (RCTs), with inconsistent results.
[Show abstract][Hide abstract] ABSTRACT: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources.
Journal of Medical Internet Research 09/2014; 16(9):e221. DOI:10.2196/jmir.3763 · 3.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chinese herbal medicine (CHM) has been widely used as an adjunct to western medicine in treating angina in China. We carried out this systematic review to evaluate the effectiveness of CHM on top of western medicine for angina. This meta-analysis included 46 randomized control trials with 4212 patients. For trials that included stable angina patients, the CHM group had significant lower incidence of total heart events (relative risk (RR) = 0.50, 95% confidence interval (CI) 0.33-0.78), myocardial infarction (RR = 0.32, 95% CI 0.14-0.72), heart failure (RR = 0.37, 95% CI 0.15-0.91), and angina (RR = 0.46, 95% CI 0.30-0.71) than that of control group. For trials that included unstable angina patients, CHM led to significantly lower occurrence of total heart events (RR = 0.46, 95% CI 0.32-0.66), myocardial infarction (RR = 0.37, 95% CI 0.26-0.54), and angina (RR = 0.36, 95%CI 0.26-0.51). Likewise, for trials that included stable or unstable angina patients, the rates of myocardial infarction (RR = 0.34, 95% CI 0.17-0.68) and angina (RR = 0.46, 95% CI 0.30-0.70) in CHM group were significantly lower than that in control group. In conclusion, CHM is very likely to be able to improve the survival of angina patients who are already receiving western medicine.
Evidence-based Complementary and Alternative Medicine 12/2013; 2013(7499):673193. DOI:10.1155/2013/673193 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Systematic reviews (SRs) that fail to search non-English databases may miss relevant studies and cause selection bias. The bias may be particularly severe in SRs of traditional Chinese medicine (TCM) as most randomized controlled trials (RCT) in TCM are published and accessible only in Chinese. In this study we investigated how often Chinese databases were not searched in SRs of TCM, how many trials were missed, and whether a bias may occur if Chinese databases were not searched. We searched 5 databases in English and 3 in Chinese for RCTs of Chinese herbal medicine for coronary artery disease and found that 96.64% (115/119) eligible studies could be identified only from Chinese databases. In a random sample of 80 Cochrane reviews on TCM, we found that Chinese databases were only searched in 43 or 53.75%, in which almost all the included studies were identified from Chinese databases. We also compared SRs of the same topic and found that they may draw a different conclusion if Chinese databases were not searched. In conclusion, an overwhelmingly high percentage of eligible trials on TCM could only be identified in Chinese databases. Reviewers in TCM are suggested to search Chinese databases to reduce potential selection bias.
Evidence-based Complementary and Alternative Medicine 10/2013; 2013(6964):812179. DOI:10.1155/2013/812179 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The World Health Organization reported in 2011that irrational use of medicines was a serious global problem that is wasteful and harmful. The worst is use of ineffective or harmful interventions which should not be used at all. However, little is known about the changes that 20 years of evidence-based medicine has made particularly in reducing use of ineffective interventions. We surveyed clinicians in China to show how often ineffective interventions were still used in practice.
3,246 clinicians from 24 tertiary hospitals were surveyed in person and another 3,063 through an online survey between 2006-2007. The main outcomes are prescription by a clinician, and use in a patient of, an ineffective intervention and of a matched effective intervention in patients with the same disease. 129 ineffective interventions for 68 diseases were identified from the BMJ Clinical Evidence and included in the survey. One effective intervention was identified for each disease and a total of 68 effective interventions were thus also included. The frequency of use of effective interventions was used as a reference for that of ineffective intervention.
The mean prescription rate by clinicians is 59.0% (95% confidence interval (95% CI): 58.6% to 59.4%) and 81.0% (95% CI: 80.6% to 81.4%) respectively for ineffective and effective interventions. The mean frequency of use in patients is 31.2% (95% CI: 30.8% to 31.6%) and 56.4% (95% CI: 56.0% to 56.8%) for ineffective and effective interventions respectively. The relative reduction in use of ineffective interventions as compared with that of matched effective interventions is 27.2% (95% CI: 27.0% to 27.4%) and 44.7% (95% CI: 44.3% to 45.1%) for clinician's prescription and use in patients respectively. 8.6% ineffective interventions were still routinely used in practice.
Ineffective interventions were still commonly used. Efforts are necessary to further reduce and eventually eliminate ineffective interventions from practice.
PLoS ONE 03/2013; 8(3):e52159. DOI:10.1371/journal.pone.0052159 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
This study aims to comprehensively summarize the currently available evidences on the efficacy and safety of gemcitabine plus erlotinib for treating advanced pancreatic cancer.
PubMed, EMBASE, The Cochrane Library and abstracts of recent major conferences were systematically searched to identify relevant publications. Studies that were conducted in advanced pancreatic cancer patients treated with gemcitabine plus erlotinib (with or without comparison with gemcitabine alone) and reporting objective response rate, disease control rate, progression-free survival, time-to-progression, overall survival, 1-year survival rate and/or adverse events were included. Data on objective response rate, disease control rate, 1-year survival rate and adverse events rate, respectively, were combined mainly by using Meta-Analyst software with a random-effects model. Data on progression-free survival, time-to-progression and overall survival were summarized descriptively. Sixteen studies containing 1,308 advanced pancreatic cancer patients treated with gemcitabine plus erlotinib were included. The reported median progression-free survival (or time-to-progression), median overall survival, 1-year survival rates, objective response rates and disease control rates were 2–9.6 months, 5–12.5 months, 20%–51%, 0%–28.6% and 25.0%–83.3%, respectively. The weighted 1-year survival rate, objective response rate and disease control rate based on studies reporting robust results were 27.9%, 9.1% and 57.0%, respectively. According to the studies with relevant data, the incidences of total and severe adverse events were 96.3% and 62.9%, respectively. The most frequently reported adverse events were leucopenia, rash, diarrhea, vomitting, neutropenia, thrombocytopenia, anaemia, stomatitis, drug-induced liver injury, fatigue and fever. Compared with gemcitabine alone, the progression-free survival and overall survival with gemcitabine plus erlotinib were significantly longer, but there were also more deaths and interstitial lung disease-like syndrome related to this treatment.
Gemcitabine plus erlotinib represent a new option for the treatment of advanced pancreatic cancer, with mild but clinically meaningful additive efficacy compared with gemcitabine alone. Its safety profile is generally acceptable, although careful management is needed for some specific adverse events.
PLoS ONE 03/2013; 8(3):e57528. DOI:10.1371/journal.pone.0057528 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The authors conducted a systematic review and meta-analysis to examine whether patients who had metastatic colorectal cancer (mCRC) with the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G13D mutation (an amino acid substitution at position 13 in KRAS from a glycine to an aspartic acid) and received cetuximab treatment had better clinical outcomes than patients who had mCRC tumors with KRAS codon 12 mutations.
Relevant studies were identified by a search of MEDLINE, EMBASE, the Chinese Biomedical Database, and Wan Fang Digital Journals from inception to October 2011. The primary clinical outcomes included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The pooled relative risk (RR) or hazard ratio (HR) was estimated by using fixed-effects or random-effects models according to heterogeneity between studies.
Ten studies were considered eligible that included 1487 patients with mCRC. Patients who had tumors with the KRAS p.G13D mutation had a significantly higher ORR (10 studies; RR, 1.642; 95% confidence interval [CI], 1.131-2.384), longer PFS (1 study; HR, 0.54; 95% CI, 0.36-0.81), and longer OS (1 study; HR, 0.52; 95% CI, 0.33-0.80) than patients who had tumors with KRAS codon 12 mutations. Compared with patients who had KRAS wild-type tumors, patients with the p.G13D mutation had a significantly lower ORR (9 studies; RR, 0.540; 95% CI, 0.381-0.765) and nonsignificantly shorter PFS (1 study; HR, 0.99; 95% CI, 0.68-1.45) and OS (1 study; HR, 1.01; 95% CI, 0.66-1.54).
Patients who had mCRC with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations. However, because of the limited sample sizes in the current meta-analysis, these results should be interpreted with caution.
Cancer 02/2013; 119(4). DOI:10.1002/cncr.27804 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epidermal growth factor receptor gene copy number (EGFR GCN) has been heavily investigated as a potential predictive biomarker for the treatment of metastatic colorectal cancer (mCRC) with anti-EGFR monoclonal antibodies (MAbs). The objective of this study was to systematically review current evidences on this issue.
PubMed, EMBASE, The Cochrane Library, Chinese Biomedical Literature Database, Wanfang Data, and the conference abstracts of American Society of Clinical Oncology and European Society of Medical Oncology were comprehensively searched. Studies that reported the objective response rate (ORR), progression-free survival, and/or overall survival of mCRC patients treated with anti-EGFR MAbs, stratified by EGFR GCN status, were included. The effect measures for binary outcome (response) and time-to-event outcomes (progression-free survival and overall survival) were risk difference and hazard ratio, respectively. Statistical heterogeneity among the studies was assessed by the Cochran's Q-test and the I2 statistic. If appropriate, a quantitative synthesis of data from different studies would be conducted with a random-effects model.
Nineteen eligible studies were identified. The criteria for increased EGFR GCN (GCN+) were highly inconsistent across different studies. The prevalence of GCN + ranged from 6.9% to 88.9%, and the difference in ORR between patients with GCN + and those with non-increased EGFR GCN (GCN-) varied from -28% to 84%. Because of the significant heterogeneity, no quantitative synthesis of data was performed. There was a general trend towards higher ORR in patients with GCN+. The difference in ORRs between patients with GCN + and those with GCN- was even greater in KRAS wild-type patients, while in KRAS mutated patients the difference often did not exist. Almost all patients with EGFR amplification responded to the treatment. However, the prevalence of EGFR amplification was generally low. Incomplete data on progression-free survival and overall survival seemingly supported the findings on ORR.
Although increased EGFR GCN is generally associated with a better outcome of anti-EGFR MAbs treatment, especially among patients with wild-type KRAS, the clinical utility of this biomarker for selecting recipients of anti-EGFR MAbs would be severely limited by the heterogeneous scoring system and the poor reproducibility of EGFR GCN enumeration due to technical reasons.