Genetic risk factors for renal failure among north Indian ESRD patients

ObjectivesAngiotensin converting enzyme (ACE), G-Protein couple receptor (G-Prot), endothelial nitric oxide synthase (ecNOS), Leptin ? 2548G/A and uncoupling protein (UCP2) are potent regulators of intra renal hemodynamics and may be the causative factors contributing to the deterioration of renal functions. In recent years few studies have been published to show the association of these markers with the end stage renal disease (ESRD). Our study was designed to see the role of different genetic factors individually and synergistically in the progression of renal failure.Design and methodsThe genotypes of these markers were determined by PCR and RFLP. The gene frequencies of ACE, G-protein, ecNOS, Leptin and UCP2 in 184 ESRD patients and 569 healthy controls from North India were compared.ResultsThere was a significant difference between ESRD patients and control groups both in the biochemical parameters and genotype frequencies. The genotype distribution of ACE in patients was significantly different from the controls (p = 0.0001; OR = 9.428; 95% CI = 4.56–19.492). There was no difference observed for the GNB3-825 TT genotype and for ecNOS aa genotype in patient and control groups. The distribution of Leptin ? 2548G/A genotype and UCP2 genotype in patients were significantly different from that of controls (p = 0.0013; OR = 2.804; 95% CI = 1.501–5.237 and p = 0.0001; OR = 8.853; 95% CI = 3.458–22.667 respectively).ConclusionsOur results propose that the ACE-DD, Leptin AA and UCP2-DD genotype may be potential genetic markers for predicting the causation and progression of chronic renal failures.     

Common variant in GAB2 is associated with late-onset Alzheimer's disease in Han Chinese

BackgroundGRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population.MethodsThe study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry.ResultsThe C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR = 1.33, 95% CI = 1.04–1.72, P = 0.029). Significance was observed in APOEε4 carriers (genotype P = 0.039, allele P = 0.016). While in APOE ε4 non-carriers, significant differences were observed in alleles (P = 0.039) but not in genotypes (P = 0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR = 2.58, 95% CI = 1.22–5.45, P = 0.013) and additive model (OR = 1.38, 95% CI = 1.05–1.80, P = 0.020) after adjusting for age, gender, and the APOE ε4 status.ConclusionsOur findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.     

Association of exonic variants of Klotho with metabolic syndrome in Asian Indians

BackgroundKlotho, an anti-aging gene, is a functional candidate for metabolic syndrome. We conducted a cross-sectional study to evaluate the association of the genetic variants of Klotho with metabolic syndrome and surrogates of insulin resistance in Asian Indians.MethodsWe recruited 428 clinically normal subjects for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism.ResultsSignificant and borderline associations of the KL-VS (OR = 15.88 [95%CI, 2.56–98.70], p = 0.003) and C1818T (OR = 0.28 [95%CI, 0.07–1.07], p = 0.063) variants of the Klotho gene, respectively, were observed with metabolic syndrome. The association of the KL-VS variant with metabolic syndrome could be linked to its observed influence on high blood glucose (OR = 6.92 [95% CI = 1.75–27.44], p = 0.006), high blood pressure (OR = 5.21 [95%CI = 1.00–38.43], p = 0.046), insulin resistance (OR = 3.59, [95%CI = 1.01–12.79], p = 0.048) and trend towards its association with hypertriglyceridemia (OR = 3.69 [95%CI = 0.92–14.77], p = 0.065).ConclusionsThe genetic variants of Klotho might predict risk for metabolic syndrome and insulin resistance in Asian Indians. However, larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of metabolic syndrome.     

Association of the TNF-α -308G/A polymorphism with family history of type 2 diabetes mellitus in a Mexican population

AimsWe examined the possible association of the ? 308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2.MethodsWe studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP.ResultsThe frequency of TNF-α ? 308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR) = 5.24; 95% confidence interval (CI) = 1.9–15.8, p < 0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR = 0.77; CI = 0.3–1.7, p = 0.4). Logistic regression analysis showed the association of TNF-α ? 308G/A polymorphism with DM2 family history (OR = 5.80; CI = 1.77–18.98, p < 0.0003).ConclusionsOur results suggest that TNF-α ? 308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.     

HER2 codon 655 polymorphism is associated with advanced uterine cervical carcinoma

Objectives:It has been suggested that overexpression of HER2 in advanced cervical tumors can be considered an independent predictor of poor patient outcome.Design and methods:Employing PCR-RFLPs, we examined the distribution of HER2 Ile655Val (rs 1136201) genotypes and alleles in patients with advanced cervical cancer (n = 109) and controls (n = 220).Results:Odds ratio (OR) for patients with advanced cervical cancer with the HER2 Val/Val homozygous or Val/Ile heterozygous state was 1.778 (95% CI = 1.117–2.830, p = 0.0176). We also observed an association of the HER2 Val/Val genotype with advanced cervical cancer in the patient group OR = 3.706 (95% CI = 1.061–12.950, p = 0.0459). However, we did not find a significant association between the distribution of genotypes or alleles and cancer characteristics for the HER2 Ile655Val polymorphism.Conclusions:Our results indicate that the HER2 655Val variant may be associated with the incidence of advanced cervical cancer.     

The RANTES gene promoter polymorphisms are associated with the risk of atherothrombotic cerebral infarction in Northern Han Chinese

BackgroundRegulated upon activation, normal T-cell expressed and secreted (RANTES) plays an important role in the inflammatory process. This study is aimed at evaluating the potential association of the ? 403G/A (rs2107538) and ? 28C/G (rs2280788) polymorphisms of the RANTES gene promoter with the risk of atherothrombotic cerebral infarction (ACI) in Northern Han Chinese.MethodA total of 314 patients with ACI and 389 unrelated aged-matched healthy controls were recruited. Their genotypes of the RANTES gene promoter ? 403G/A (rs2107538) and ? 28C/G (rs2280788) were analyzed by multiplex polymerase chain reaction (multiplex PCR) and multiplex SNaPshot analysis. The potential association of genotyping and allele frequencies with ACI in this population was assessed statistically.ResultsThe frequencies of ? 403AA genotype and A allele in ACI male patients were significantly higher than that in healthy controls (P = 0.007, P = 0.009, respectively). Female patients were not different. Multiple logistic regression analysis revealed that the ? 403AA genotype in males was significantly associated with an increased risk of ACI, even after adjusting for confounding factors (OR = 4.344; 95% CI = 1.969–9.582; P < 0.001). Although there was no significant association of the ? 28C/G polymorphism with ACI, the A-₄₀₃C-₂₈ haplotype was significantly associated with an increased risk of ACI in Han Chinese [OR = 1.56, 95% CI = 1.23–1.98, P < 0.001].ConclusionsOur data suggest that the ? 403AA genotype and A allele of the RANTES promoter were associated with increased risk for the development of ACI in male Northern Han Chinese.     

Predictors of recruited melanoma families into a behavioral intervention project

BackgroundExamination of families represents an important priority in health research. In this paper we report on individual and family-level factors associated with enrollment in a cancer prevention research project. We approached families affected by melanoma for possible participation in a randomized controlled trial of a web-based communication and support intervention.MethodsWe recruited three family members per family for assessment — the melanoma case, a first-degree relative (FDR), and a relative who is a parent of a child age 18 or younger. Recruitment involved three steps: requesting the physician's consent to approach the melanoma case, approaching the case to request their participation and family contact information, and they approaching the FDRs and parents.ResultsOf the 1380 families approached, 313 were enrolled, 263 were excluded because we could not find or contact a family member (FDR or parent), 331 did not have eligible family members, and 473 refused. The most frequently noted reason for refusal was being too busy or having no time. The primary predictors of participation for cases (OR = 1.6; CI = 1.01–2.51) and FDRs (OR = 2.15; CI = 1.11–4.13) included higher educational attainment. FDRs were more likely to enroll if they were female (OR = 1.77; CI = 1.1–.85) and parents were more likely to enroll if the case had been diagnosed more recently (OR = 3.3; CI = 1.9–5.93), if the parent was partnered (OR = 4.37; CI = 1.86–10.26), and if the parent lived in the same city as the case (OR = 2.88; CI = 1.08–7.68).ConclusionsThe results can provide information on potential directions for future family recruitment.     

The paraoxonase L55M and Q192R gene polymorphisms and myocardial infarction in a Tunisian population

ObjectivesIn the present study, we examined a possible association between the PON1 Q192R and L55M polymorphisms and myocardial infarction (MI) in a sample of the Tunisian population.Design and methodsThree hundred and ten patients with MI and 375 controls were recruited. Paraoxonase gene polymorphisms at codon 192 and 55 were analyzed by PCR-RFLP.ResultsGenotype distributions and allele frequencies of L55M were similar among the control and MI groups. For the Q192R polymorphism patients with MI had significantly higher frequency of the RR genotype compared to controls [17.1% vs. 10.9%; OR (95% CI), 1.93 (1.24–3.02); p = 0.004]. The MI patient group showed a significantly higher frequency of the R allele compared to the controls [38% vs. 30%; χ² = 10.74, p = 0.001]. The association between the PON1 Q192R polymorphism and MI remained significant after adjustment for other well-established cardiovascular risk factors.ConclusionsThe present study showed a significant and independent association between the PON1 Q192R polymorphism (presence of R allele) and MI in the Tunisian population.     

Folate and choline metabolism gene variants and development of uterine cervical carcinoma

ObjectiveIt has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.Design and methodEmploying PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n = 124) and controls (n = 168).ResultsThe odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI = 0.1780–1.054; p = 0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI = 0.3622–0.924; p = 0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p = 0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.ConclusionOur results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.     

Investigation of the effect of donor platelet endothelial cell adhesion molecule 1 polymorphism on the graft-vs.-host disease occurrence in Tunisian recipients of hematopoietic stem cells

ObjectiveThe aim of this study is to examine the effect of donor PECAM-1 alleles and haplotypes for the SNPs L98V, S536N, and R643G on the occurrence of GVHD in Tunisian recipients of HSCs.Design and methodsThis study enrolled 102 patients and their 102 respective HLA-identical sibling donors of HSCs. The PECAM-1 SNPs genotyping assay was performed using sets of sequence specific primers (SSP-PCR).ResultsThe single marker association analysis showed that the L98 allele, in a recessive genetic model, may be a potential risk factor only for acute GVHD (p = 0.036, OR = 2.580, 95% C.I. = 1.053–6.326). However, the haplotype analysis showed a lack of association between donor's PECAM-1 SNPs and GVHD incidence in recipient.ConclusionThe homozygosity state for donor PECAM-1 L98 allele may be a significant risk factor for acute GVHD. This is probably due to its action on the function of donor leukocytes especially during the extravasation process.     

The association between miR-146a gene rs2910164 polymorphism and gastric cancer risk: A meta-analysis

PurposeStudies have demonstrated that single nucleotide polymorphisms (SNPs) in miRNAs may lead to varying functional outcomes by altering miRNAs expression, even leading to the development of cancers. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to gastric cancer has been studied during the recent years, but the results are still inconclusive and inconsistent. We performed a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphism and the risk of gastric cancer.Materials and methodsThe databases of PubMed, MEDLINE and Web of Science were searched for suitable studies. A total of 8 published case–control studies on miR-146a rs2910164 polymorphism and gastric cancer risk including 4308 cases and 6370 controls were included.ResultsOverall, significant association was observed between rs2910164 and gastric cancer risk in allele model (OR = 1.11, 95% CI = 1.02–1.21); homozygote model (OR = 1.26, 95% CI = 1.10–1.43) and dominant model (OR = 1.21, 95% CI = 1.09–1.34). Stratified analysis by ethnicity showed significant association between rs2910164 polymorphism and gastric cancer susceptibility in Asians (OR = 1.10, 95% CI = 1.00–1.23 for G vs. C; OR = 1.25, 95% CI = 1.09–1.43 for GG vs. CC; OR = 1.19, 95% CI = 1.07–1.33 for GG vs. GC+CC, respectively). When stratified by genotyping methods and sample size, increased gastric cancer risk was only observed with the method by TaqMan and the sample size more than 1000.ConclusionIn summary, this meta-analysis indicated that miR-146a rs2910164 polymorphism was associated with the susceptibility to gastric cancer, especially in Asian population.     

Quantitative analysis of chest compression interruptions during in-hospital resuscitation of older children and adolescents

AimTo quantitatively describe pauses in chest compression (CC) delivery during resuscitation from in-hospital pediatric and adolescent cardiac arrest. We hypothesized that CPR error will be more likely after a chest compression provider change compared to other causes for pauses.MethodsCPR recording/feedback defibrillators were used to evaluate CPR quality for victims ≥8 years who received CPR in the PICU/ED. Audiovisual feedback was supplied in accordance with AHA targets. Etiology of CC pauses identified by post-event debriefing/reviews of stored CPR quality data.ResultsAnalysis yielded 205 pauses during 304.8 min of CPR from 20 consecutive cardiac arrests. Etiologies were: 57.1% for provider switch; 23.9% for pulse/rhythm analysis; 4.4% for defibrillation; and 14.6% “other.” Provider switch accounted for 41.2% of no-flow duration. Compared to other causes, CPR epochs following pauses due to provider switch were more likely to have measurable residual leaning (OR: 5.52; CI⁹⁵: 2.94, 10.32; p < 0.001) and were shallower (43 ± 8 vs. 46 ± 7 mm; mean difference: ?2.42 mm; CI⁹⁵: ?4.71, ?0.13; p = 0.04). Individuals performing continuous CPR ≥ 120 s as compared to those switching earlier performed deeper chest compressions (42 ± 6 vs. 38 ± 7 mm; mean difference: 4.44 mm; CI⁹⁵: 2.39, 6.49; p < 0.001) and were more compliant with guideline depth recommendations (OR: 5.11; CI⁹⁵: 1.67, 15.66; p = 0.004).ConclusionsProvider switches account for a significant portion of no-flow time. Measurable residual leaning is more likely after provider switch. Feedback systems may allow some providers to continue high quality CPR past the recommended switch time of 2 min during in-hospital resuscitation attempts.     

Monocyte chemoattractant protein 1-2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.     

Synergistic effects of the polymorphisms in the PAI-1 and IL-6 genes with smoking in determining their associated risk with coronary artery disease

ObjectivesTo assess the relationship between IL-6 and PAI-1 polymorphisms and coronary artery disease (CAD) and to observe the interactions between these polymorphic variants and smoking in the CAD risk.Design and methodThe study population consisted of 178 patients with angiographically documented CAD and 202 blood donors. The analyses of genetic polymorphisms were performed using the PCR-RFLP method.ResultsThe frequency of PAI-1 5G allele was higher in the entire CAD group than in control group (p = 0.04, OR = 1.35). Also the 5G allele carriers (4G5G + 5G5G) were more frequent in patients than in controls (p = 0.03, OR = 1.93). The number of women carrying 5G allele was again significantly higher among patients (OR = 10.95 p = 0.0075). The IL-6 C allele frequency was higher only in the CAD male subgroup (p = 0.035, OR = 1.44). We found synergistic and cumulative effects between specific genotype patterns and smoking in determining the risk of CAD, especially between PAI-1(4G5G + 5G5G)+IL-6(CC) and smoking (SIM = 4.18 and p = 0.0005, OR = 9.20, respectively).ConclusionsThere are synergistic and cumulative effects of 5G allele of PAI-1 polymorphism and C allele of IL-6 polymorphism with smoking in determining their associated risk with CAD.     

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes

Background and aimsMetabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity.Design and methodsEighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated.ResultsAs expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as > 250% ml^? 1 h^? 1. The predictive variables of high CETP were non-HDL-C ≥ 160 mg/dl (OR = 11.1;95%IC = 3.3–38.2;p < 0.001) and HOMA-IR > 2.1 (OR = 4.4;95%IC = 1.3–14.8;p < 0.05).ConclusionsHigh non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.     

TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: a meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients

BackgroundAcute coronary syndromes (ACS) represent a difficult challenge for physicians. Risk scores have become the cornerstone in clinical and interventional decision making.Methods and resultsPubMed was systematically searched for ACS risk score studies. They were divided into ACS studies (evaluating Unstable Angina; UA, Non ST Segment Elevation Myocardial Infarction; NSTEMI, and ST Segment Elevation Myocardial Infarction; STEMI), UA/NSTEMI studies or STEMI studies. The c-statistics of validation studies were pooled when appropriate with random-effect methods. 7 derivation studies with 25,525 ACS patients and 15 validation studies including 257,654 people were formally appraised. Pooled analysis of GRACE scores, both at short (0.82; 0.80–0.89 I.C 95%) and long term follow up (0.84; 0.82–0.87; I.C 95%) showed the best performance, with similar results to Simple Risk Index (SRI) derivation cohorts at short term. For NSTEMI/UA, 18 derivation studies with 56,560 patients and 18 validation cohorts with 56,673 patients were included. Pooled analysis of validations studies showed c-statistics of 0.54 (95% CI = 0.52–0.57) and 0.67 (95% CI = 0.62–0.71) for short and long term TIMI validation studies, and 0.83 (95% CI = 0.79–9.87) and 0.80 (95% CI = 0.74–0.89) for short and long term GRACE studies. For STEMI, 15 studies with 134,557 patients with derivation scores, and 17 validation studies with 187,619 patients showed a pooled c-statistic of 0.77 (95% CI = 0.71–0.83) and 0.77 (95% CI = 0.72–0.85) for TIMI at short and long term, and a pooled c-statistic of 0.82 (95% CI = 0.81–0.83) and 0.81 (95% CI = 0.80–0.82) for GRACE at short and long terms respectively.ConclusionsTIMI and GRACE are the risk scores that up until now have been most extensively investigated, with GRACE performing better. There are other potentially useful ACS risk scores available however these have not undergone rigorous validation. This study suggests that these other scores may be potentially useful and should be further researched.     

Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population

BackgroundRed cell distribution width (RDW) is associated with morbidity and mortality in coronary artery disease (CAD), but the connection of RDW with chronic inflammation is equivocal.MethodsIn 1,489 patients with CAD and 8.4–15.2 years of follow-up all-cause mortality and RDW were studied using Cox regression. RDW and its associations with inflammation, liver function, renal function, and body mass were assessed. A population of 449 normal (No-CAD) patients also was evaluated.ResultsRDW predicted all-cause mortality in a step-wise manner (HR = 1.37 per quintile; 95% CI = 1.29, 1.46; p-trend < 0.001). A significant but meaningless correlation between RDW and high-sensitivity C-reactive protein (hsCRP) was identified (r = 0.181; p < 0.001). With full adjustment, RDW remained significant (p-trend < 0.001) and the strongest predictor of mortality among all factors included in the model. RDW also strongly predicted all-cause mortality in the normal control population (HR = 1.33 per quintile, CI = 1.15, 1.55; p-trend < 0.001), but hsCRP did not predict mortality among normal controls.ConclusionsRDW was associated with mortality in patients with CAD and may provide clinically useful prognostication. Although RDW was correlated with hsCRP, they were independent predictors of mortality. RDW has been incorporated into risk prediction tool using data from basic chemistries available at: http://intermountainhealthcare.org/IMRS.     

Effectiveness of automated notification and customer service call centers for timely and accurate reporting of critical values: A laboratory medicine best practices systematic review and meta-analysis

ObjectiveTo conduct a systematic review of the evidence available in support of automated notification methods and call centers and to acknowledge other considerations in making evidence-based recommendations for best practices in improving the timeliness and accuracy of critical value reporting.Design and methodsThis review followed the Laboratory Medicine Best Practices (LMBP) review methods (Christenson, et al. 2011). A broad literature search and call for unpublished submissions returned 196 bibliographic records which were screened for eligibility. 41 studies were retrieved. Of these, 4 contained credible evidence for the timeliness and accuracy of automatic notification systems and 5 provided credible evidence for call centers for communicating critical value information in in-patient care settings.ResultsStudies reporting improvement from implementing automated notification findings report mean differences and were standardized using the standard difference in means (d = 0.42; 95% CI = 0.2–0.62) while studies reporting improvement from implementing call centers generally reported criterion referenced findings and were standardized using odds ratios (OR = 22.1; 95% CI = 17.1–28.6).ConclusionsThe evidence, although suggestive, is not sufficient to make an LMBP recommendation for or against using automated notification systems as a best practice to improve the timeliness of critical value reporting in an in-patient care setting. Call centers, however, are effective in improving the timeliness of critical value reporting in an in-patient care setting, and meet LMBP criteria to be recommended as an “evidence-based best practice.”DisclaimerThe findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (CDC/ATSDR).