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1.
2.

Introduction

Ultra-deep pyrosequencing (UDPS) has been used to detect minority variants within HIV-1 populations. Some aspects of the quality and reproducibility of UDPS have been previously evaluated, but comprehensive studies are still needed.

Principal Finding

In this study the UDPS technology (FLX platform) was evaluated by analyzing a 120 base pair fragment of the HIV-1 pol gene from plasma samples from two patients and artificial mixtures of molecular clones. UDPS was performed using an optimized experimental protocol and an in-house data cleaning strategy. Nine samples and mixtures were analyzed and the average number of reads per sample was 19,404 (range 8,858–26,846). The two patient plasma samples were analyzed twice and quantification of viral variants was found to be highly repeatable for variants representing >0.27% of the virus population, whereas some variants representing 0.11–0.27% were detected in only one of the two UDPS runs. Bland-Altman analysis showed that a repeated measurement would have a 95% likelihood to lie approximately within ±0.5 log10 of the initial estimate. A similar level of agreement was observed for variant frequency estimates in forward vs. reverse sequencing direction, but here the agreement was higher for common variants than for rare variants. UDPS following PCR amplification with alternative primers indicated that some variants may be incorrectly quantified due to primer-related selective amplification. Finally, the in vitro recombination rate during PCR was evaluated using artificial mixtures of clones and was found to be low. The most abundant in vitro recombinant represented 0.25% of all UDPS reads.

Conclusion

This study demonstrates that this UDPS protocol results in low experimental noise and high repeatability, which is relevant for future research and clinical use of the UDPS technology. The low rate of in vitro recombination suggests that this UDPS system can be used to study genetic variants and mutational linkage.  相似文献   

3.

Aims

The aims of this study were to develop bioinformatics tools to explore ultra-deep pyrosequencing (UDPS) data, to test these tools, and to use them to determine the optimum error threshold, and to compare results from UDPS and cloning based sequencing (CBS).

Methods

Four serum samples, infected with either genotype D or E, from HBeAg-positive and HBeAg-negative patients were randomly selected. UDPS and CBS were used to sequence the basic core promoter/precore region of HBV. Two online bioinformatics tools, the “Deep Threshold Tool” and the “Rosetta Tool” (http://hvdr.bioinf.wits.ac.za/tools/), were built to test and analyze the generated data.

Results

A total of 10952 reads were generated by UDPS on the 454 GS Junior platform. In the four samples, substitutions, detected at 0.5% threshold or above, were identified at 39 unique positions, 25 of which were non-synonymous mutations. Sample #2 (HBeAg-negative, genotype D) had substitutions in 26 positions, followed by sample #1 (HBeAg-negative, genotype E) in 12 positions, sample #3 (HBeAg-positive, genotype D) in 7 positions and sample #4 (HBeAg-positive, genotype E) in only four positions. The ratio of nucleotide substitutions between isolates from HBeAg-negative and HBeAg-positive patients was 3.5∶1. Compared to genotype E isolates, genotype D isolates showed greater variation in the X, basic core promoter/precore and core regions. Only 18 of the 39 positions identified by UDPS were detected by CBS, which detected 14 of the 25 non-synonymous mutations detected by UDPS.

Conclusion

UDPS data should be approached with caution. Appropriate curation of read data is required prior to analysis, in order to clean the data and eliminate artefacts. CBS detected fewer than 50% of the substitutions detected by UDPS. Furthermore it is important that the appropriate consensus (reference) sequence is used in order to identify variants correctly.  相似文献   

4.

Background

Preeclampsia, characterized by hypertension and proteinuria, is a multifactorial disease caused by complex interactions between environmental and genetic factors. A recent genome-wide association study of blood pressure reported an association between hypertension and rs11646213. This study evaluated the association between preeclampsia and rs11646213.

Methods

A total of 454 cases and 460 controls were recruited to participate in this study. The single nucleotide polymorphism (SNP) rs11646213 was genotyped by polymerase chain reaction (PCR) and direct sequencing.

Results

The allele frequency of rs11646213 was significantly different between the preeclampsia and control groups (P = 0.017, OR = 1.36, 95% CI = 1.06–1.76). Differences were particularly significant in the severe preeclampsia subgroup (P = 0.002, OR = 1.54, 95% CI = 1.17–2.03) and the early-onset preeclampsia subgroup (P = 0.004, OR = 1.57, 95% CI = 1.16–2.13). Genotyping analysis showed that the T allele of rs11646213 could confer a risk for preeclampsia, severe preeclampsia and early-onset preeclampsia.

Conclusions

Rs11646213 upstream of the CDH13 gene is associated with preeclampsia in Han Chinese women.  相似文献   

5.

Background

The HIV-1 nucleoside RT inhibitor (NRTI)-resistance mutation, K65R confers intermediate to high-level resistance to the NRTIs abacavir, didanosine, emtricitabine, lamivudine, and tenofovir; and low-level resistance to stavudine. Several lines of evidence suggest that K65R is more common in HIV-1 subtype C than subtype B viruses.

Methods and Findings

We performed ultra-deep pyrosequencing (UDPS) and clonal dideoxynucleotide sequencing of plasma virus samples to assess the prevalence of minority K65R variants in subtype B and C viruses from untreated individuals. Although UDPS of plasma samples from 18 subtype C and 27 subtype B viruses showed that a higher proportion of subtype C viruses contain K65R (1.04% vs. 0.25%; p<0.001), limiting dilution clonal sequencing failed to corroborate its presence in two of the samples in which K65R was present in >1.5% of UDPS reads. We therefore performed UDPS on clones and site-directed mutants containing subtype B- and C-specific patterns of silent mutations in the conserved KKK motif encompassing RT codons 64 to 66 and found that subtype-specific nucleotide differences were responsible for increased PCR-induced K65R mutation in subtype C viruses.

Conclusions

This study shows that the RT KKK nucleotide template in subtype C viruses can lead to the spurious detection of K65R by highly sensitive PCR-dependent sequencing techniques. However, the study is also consistent with the subtype C nucleotide template being inherently responsible for increased polymerization-induced K65R mutations in vivo.  相似文献   

6.

Introduction

Human herpesvirus 6 (HHV-6) is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6). The biological consequences of chromosomal integration by HHV-6 remain unknown.

Objective

To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors.

Methodology

A total of 293 DNA samples from children with pre-B (n = 255), pre-pre-B (n = 4), pre-T (n = 26) and undetermined (n = 8) leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR) using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content.

Results

Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35%) contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6.

Conclusion

The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p = 0.5) to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.  相似文献   

7.

Background

RNA viruses have high mutation rates and exist within their hosts as large, complex and heterogeneous populations, comprising a spectrum of related but non-identical genome sequences. Next generation sequencing is revolutionising the study of viral populations by enabling the ultra deep sequencing of their genomes, and the subsequent identification of the full spectrum of variants within the population. Identification of low frequency variants is important for our understanding of mutational dynamics, disease progression, immune pressure, and for the detection of drug resistant or pathogenic mutations. However, the current challenge is to accurately model the errors in the sequence data and distinguish real viral variants, particularly those that exist at low frequency, from errors introduced during sequencing and sample processing, which can both be substantial.

Results

We have created a novel set of laboratory control samples that are derived from a plasmid containing a full-length viral genome with extremely limited diversity in the starting population. One sample was sequenced without PCR amplification whilst the other samples were subjected to increasing amounts of RT and PCR amplification prior to ultra-deep sequencing. This enabled the level of error introduced by the RT and PCR processes to be assessed and minimum frequency thresholds to be set for true viral variant identification. We developed a genome-scale computational model of the sample processing and NGS calling process to gain a detailed understanding of the errors at each step, which predicted that RT and PCR errors are more likely to occur at some genomic sites than others. The model can also be used to investigate whether the number of observed mutations at a given site of interest is greater than would be expected from processing errors alone in any NGS data set. After providing basic sample processing information and the site’s coverage and quality scores, the model utilises the fitted RT-PCR error distributions to simulate the number of mutations that would be observed from processing errors alone.

Conclusions

These data sets and models provide an effective means of separating true viral mutations from those erroneously introduced during sample processing and sequencing.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1456-x) contains supplementary material, which is available to authorized users.  相似文献   

8.

Background

Gain-of-function mutations in the ATP-sensitive potassium channel can cause permanent neonatal diabetes mellitus (PNDM) or neonatal diabetes accompanied by a constellation of neurological symptoms (iDEND syndrome). Studies of a mouse model of iDEND syndrome revealed that cerebellar Purkinje cell electrical activity was impaired and that the mice exhibited poor motor coordination. In this study, we probed the hand-eye coordination of PNDM and iDEND patients using visual tracking tasks to see if poor motor coordination is also a feature of the human disease.

Methods

Control participants (n = 14), patients with iDEND syndrome (n = 6 or 7), and patients with PNDM (n = 7) completed three computer-based tasks in which a moving target was tracked with a joystick-controlled cursor. Patients with PNDM and iDEND were being treated with sulphonylurea drugs at the time of testing.

Results

No differences were seen between PNDM patients and controls. Patients with iDEND syndrome were significantly less accurate than controls in two of the three tasks. The greatest differences were seen when iDEND patients tracked blanked targets, i.e. when predictive tracking was required. In this task, iDEND patients incurred more discrepancy errors (p = 0.009) and more velocity errors (p  = 0.009) than controls.

Conclusions

These results identify impaired hand-eye coordination as a new clinical feature of iDEND. The aetiology of this feature is likely to involve cerebellar dysfunction. The data further suggest that sulphonylurea doses that control the diabetes of these patients may be insufficient to fully correct their neurological symptoms.  相似文献   

9.

Background

Recently, metagenomic studies have identified viable Pepper mild mottle virus (PMMoV), a plant virus, in the stool of healthy subjects. However, its source and role as pathogen have not been determined.

Methods and Findings

21 commercialized food products containing peppers, 357 stool samples from 304 adults and 208 stool samples from 137 children were tested for PMMoV using real-time PCR, sequencing, and electron microscopy. Anti-PMMoV IgM antibody testing was concurrently performed. A case-control study tested the association of biological and clinical symptoms with the presence of PMMoV in the stool. Twelve (57%) food products were positive for PMMoV RNA sequencing. Stool samples from twenty-two (7.2%) adults and one child (0.7%) were positive for PMMoV by real-time PCR. Positive cases were significantly more likely to have been sampled in Dermatology Units (p<10−6), to be seropositive for anti-PMMoV IgM antibodies (p = 0.026) and to be patients who exhibited fever, abdominal pains, and pruritus (p = 0.045, 0.038 and 0.046, respectively).

Conclusions

Our study identified a local source of PMMoV and linked the presence of PMMoV RNA in stool with a specific immune response and clinical symptoms. Although clinical symptoms may be imputable to another cofactor, including spicy food, our data suggest the possibility of a direct or indirect pathogenic role of plant viruses in humans.  相似文献   

10.

Purpose

To evaluate the factors affecting the area under the log contrast sensitivity function (AULCSF) in healthy myopic eyes.

Methods

We retrospectively examined 201 eyes of 201 consecutive subjects (age, 31.8±7.4 years (mean ± standard deviation)) with myopic refractive errors of −1.25 to −8.25 diopters (D). From the contrast sensitivity data, the area under the log contrast sensitivity function (AULCSF) was calculated. Stepwise multiple regression analysis was used to assess the factors affecting the AULCSF.

Results

The mean AULSCF was 1.09±0.09 (0.89 to 1.55). Explanatory variables relevant to the AULCSF were, in order of influence, the objective scattering index (OSI) (p = 0.018, partial regression coefficient B = –0.032) and logMAR CDVA (p = 0.022, B = –0.209) (adjusted R2 = 0.231). No significant correlation was seen with other clinical factors such as gender, manifest refraction, pupil size, lens density, corneal HOAs, or ocular HOAs.

Conclusions

Although the great majority of the variance remains unexplained, eyes with lower OSI and better CDVA are more predisposed to show higher contrast sensitivity function. These results indicate that not only CDVA but also intraocular forward scattering may play some role in predicting the contrast sensitivity function in myopic subjects.  相似文献   

11.

Background

Effective immunizations require a thorough, multi-step process, yet few studies comprehensively addressed issues around vaccination management.

Objectives

To assess variations in vaccination management and vaccination errors in primary care.

Methods

A cross sectional, web-based questionnaire survey was performed among 1157 primary physicians from North Rhine-Westphalia, Germany: a representative 10% random sample of general practitioners (n = 946) and all teaching physicians from the University Duisburg-Essen (n = 211). Four quality aspects with three items each were included: patient-related quality (patient information, patient consent, strategies to increase immunization rates), vaccine-related quality (practice vaccine spectrum, vaccine pre-selection, vaccination documentation), personnel-related quality (recommendation of vaccinations, vaccine application, personnel qualification) and storage-related quality (storage device, temperature log, vaccine storage control). For each of the four quality aspects, “good quality” was reached if all three criteria per quality aspect were fulfilled. Good vaccination management was defined as fulfilling all twelve items. Additionally, physicians’ experiences with errors and nearby-errors in vaccination management were obtained.

Results

More than 20% of the physicians participated in the survey. Good vaccination management was reached by 19% of the practices. Patient-related quality was good in 69% of the practices, vaccine-related quality in 73%, personnel-related quality in 59% and storage-related quality in 41% of the practices. No predictors for error reporting and good vaccination management were identified.

Conclusions

We identified good results for vaccine- and patient-related quality but need to improve issues that revolve around vaccine storage.  相似文献   

12.

Background

Ewing''s sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT.

Methodology

Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics.

Principal Findings

Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression.

Conclusions

We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy.  相似文献   

13.

Objective

To perform a systematic review and individual participant data meta-analysis to identify preoperative factors associated with a good seizure outcome in children with Tuberous Sclerosis Complex undergoing resective epilepsy surgery.

Data Sources

Electronic databases (MEDLINE, EMBASE, CINAHL and Web of Science), archives of major epilepsy and neurosurgery meetings, and bibliographies of relevant articles, with no language or date restrictions.

Study Selection

We included case-control or cohort studies of consecutive participants undergoing resective epilepsy surgery that reported seizure outcomes. We performed title and abstract and full text screening independently and in duplicate. We resolved disagreements through discussion.

Data Extraction

One author performed data extraction which was verified by a second author using predefined data fields including study quality assessment using a risk of bias instrument we developed. We recorded all preoperative factors that may plausibly predict seizure outcomes.

Data Synthesis

To identify predictors of a good seizure outcome (i.e. Engel Class I or II) we used logistic regression adjusting for length of follow-up for each preoperative variable.

Results

Of 9863 citations, 20 articles reporting on 181 participants were eligible. Good seizure outcomes were observed in 126 (69%) participants (Engel Class I: 102(56%); Engel class II: 24(13%)). In univariable analyses, absence of generalized seizure semiology (OR = 3.1, 95%CI = 1.2–8.2, p = 0.022), no or mild developmental delay (OR = 7.3, 95%CI = 2.1–24.7, p = 0.001), unifocal ictal scalp electroencephalographic (EEG) abnormality (OR = 3.2, 95%CI = 1.4–7.6, p = 0.008) and EEG/Magnetic resonance imaging concordance (OR = 4.9, 95%CI = 1.8–13.5, p = 0.002) were associated with a good postoperative seizure outcome.

Conclusions

Small retrospective cohort studies are inherently prone to bias, some of which are overcome using individual participant data. The best available evidence suggests four preoperative factors predictive of good seizure outcomes following resective epilepsy surgery. Large long-term prospective multicenter observational studies are required to further evaluate the risk factors identified in this review.  相似文献   

14.

Background

To investigate the distribution of intraocular pressure (IOP) and refractive errors according to age group in a representative sample of non-glaucomatous Korean adults.

Methods

A total of 7,277 adults (≥19 years) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011 underwent ophthalmic examination were divided into three groups according to age: the young- (19–39 years), middle- (40–59 years), and old- (≥60 years) age groups. Simple and multiple regression analyses between IOP and various parameters (including the refractive error) were conducted.

Results

The mean IOP of the total population was 14.0±0.1 mmHg [young: 13.9±0.1 mmHg; middle: 14.1±0.1 mmHg; old: 13.8±0.2 mmHg (P for trend = 0.085)]. Myopia and high myopia were more prevalent in the young- (70.8% and 16.1%, respectively), compared to the middle- (44.6% and 10.9%) and old- (8.9% and 2.2%) age groups. Univariate analysis in the total population showed that higher IOP was associated with myopic refractive error, the female gender, higher body mass index (BMI), diabetes, hypertension, and hypercholesterolemia (all P<0.05). In the young- and middle-age groups, higher IOP was associated with myopic refractive error, the female gender, higher BMI, hypercholesterolemia and diabetes (all P<0.05). In the old-age group, the association between IOP and refractive error was not significant (P = 0.828). In multiple linear regression analysis, similar significant relationships between the refractive error and IOP were found in the young- and middle-age groups (beta = −0.08 and −0.12; P = 0.002 and <0.001 for young- and middle-age group, respectively), but not in the old-age group (beta = 0.03; P = 0.728), after adjusting for age, gender, BMI, region of habitation, diabetes, hypertension, and hypercholesterolemia.

Conclusions

Myopic refractive error was an independent predictor of higher IOP in non- glaucomatous eyes, and the association between refractive error and IOP differed according to age.  相似文献   

15.

Objective

To compare frontal sinus cranialization to obliteration for future prevention of secondary mucocele formation following open surgery for benign lesions of the frontal sinus.

Study Design

Retrospective case series.

Setting

Tertiary academic medical center.

Patients

Sixty-nine patients operated for benign frontal sinus pathology between 1994 and 2011.

Interventions

Open excision of benign frontal sinus pathology followed by either frontal obliteration (n = 41, 59%) or frontal cranialization (n = 28, 41%).

Main Outcome Measures

The prevalence of post-surgical complications and secondary mucocele formation were compiled.

Results

Pathologies included osteoma (n = 34, 49%), mucocele (n = 27, 39%), fibrous dysplasia (n = 6, 9%), and encephalocele (n = 2, 3%). Complications included skin infections (n = 6), postoperative cutaneous fistula (n = 1), telecanthus (n = 4), diplopia (n = 3), nasal deformity (n = 2) and epiphora (n = 1). None of the patients suffered from postoperative CSF leak, meningitis or pneumocephalus. Six patients, all of whom had previously undergone frontal sinus obliteration, required revision surgery due to secondary mucocele formation. Statistical analysis using non-inferiority test reveal that cranialization of the frontal sinus is non-inferior to obliteration for preventing secondary mucocele formation (P<0.0001).

Conclusion

Cranialization of the frontal sinus appears to be a good option for prevention of secondary mucocele development after open excision of benign frontal sinus lesions.  相似文献   

16.

Background

Hyperopic undercorrection is a common clinical practice. However, less is known of its effect on the change in refractive errors and emmetropization throughout the later years of childhood.

Objectives

To evaluate the effect of spectacle correction on the change in refractive errors in hyperopic children less than 12 years of age with or without strabismus.

Data Extraction

A retrospective cohort study was performed by a computer based search of the hospital database of patients with hyperopia, accommodative esotropia or exotropia. A total of 150 hyperopic children under 12 years of age were included. Patients were classified into four groups: 1) accommodative esotropia with full correction of hyperopia, 2) exotropia with undercorrection of hyperopia, 3) orthotropia with full correction of hyperopia, 4) orthotropia with undercorrection of hyperopia. The 4 groups were matched by initial age on examination and spherical equivalent refractive errors (SER). The main outcome measure was the change in SER (Diopter/year) in both eyes after two years of follow-up.

Results

An overall negative shift in SER was noted during the follow-up period in all groups, except for the group with esotropia and full correction. The mean negative shift of hyperopia was more rapid in groups receiving undercorrection of hyperopia with or without strabismus. The amount of undercorrection of hyperopia was positively correlated to the magnitude of decrease in hyperopia in all patients (r = 0.289, P<0.001) and in the subgroup of patients with orthotropia (r = 0.304, P = 0.011). The amount of undercorrection of hyperopia was the only factor associated with a more negative shift in SER (OR, 2.414; 95% CI, 1.202–4.849; P = 0.013).

Conclusions

The amount of undercorrection is significantly correlated to the change in hyperopic refractive errors. Full correction of hyperopia may inhibit emmetropization during early and late childhood.  相似文献   

17.

Background

Methylenetetrahydrofolate reductase (MTHFR) converts 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate and affects the activity of cellular cycles participating in nucleotide synthesis, DNA repair, genome stability, maintenance of methyl pool, and gene regulation. Genetically compromised MTHFR activity has been suggested to affect male fertility. The objective of the present study was to find the impact on infertility risk of c.203G>A, c.1298A>C, and c.1793G>A polymorphisms in the MTHFR gene.

Methods

PCR-RFLP and DNA sequencing were used to genotype the common SNPs in the MTHFR gene in 630 infertile and 250 fertile males. Chi-square test was applied for statistical comparison of genotype data. Linkage disequilibrium between the SNPs and the frequency of common haplotypes were assessed using Haploview software. Biochemical levels of total homocysteine (tHcy) and folic acid were measured. Meta-analysis on c.1298A>C polymorphism was performed using data from ten studies, comprising 2734 cases and 2737 controls.

Results

c.203G>A and c.1298A>C were found to be unrelated to infertility risk. c.1793G>A was protective against infertility (P = 0.0008). c.677C>T and c.1793G>A were in significant LD (D’ = 0.9). Folic acid and tHcy level did not correlate with male infertility. Pooled estimate on c.1298A>C data from all published studies including our data showed no association of this polymorphism with male infertility (Odds ratio = 1.035, P = 0.56), azoospermia (Odds ratio = 0.97, P = 0.74), or oligoasthenoteratozoospermia (Odds ratio = 0.92, p = 0.29). Eight haplotypes with more than 1% frequency were detected, of which CCGA was protective against infertility (p = 0.02), but the significance of the latter was not seen after applying Bonferroni correction.

Conclusion

Among MTHFR polymorphisms, c.203G>A and c.1298A>C do not affect infertility risk and c.1793G>A is protective against infertility. Haplotype analysis suggested that risk factors on the MTHFR locus do not extend too long on the DNA string.  相似文献   

18.
19.

Background

Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury.

Study Design

A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3rd quarter 2011). Two reviewers identified relevant trials and abstracted data.

Settings and Population

Trials including patients undergoing a contrast enhanced procedure.

Selection Criteria

Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion.

Intervention

Oral route of volume expansion compared to the intravenous route.

Outcomes

Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death.

Results

Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I2 = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I2 = 0).

Limitations

Small number of studies identified; lack of hard clinical outcomes.

Conclusion

The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion.  相似文献   

20.
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