Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis

BackgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.ObjectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.MethodsSystematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (IV) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I² statistics.ResultsForty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of IV iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I² = 53.6%] and versus IV iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I² = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus IV iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I² = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I² = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.ConclusionsOur meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.     

Sequential Analysis of Survival Times in Clinical Trials

This paper provides a synopsis of statistical methods which can be used for the sequential analysis of possibly censored survival times in clinical trials. Especially, results on the asymptotic behaviour of the Breslow-Haug statistic and on the sequential version of the logrank statistic are presented in a standardized terminology. In addition, formulae for the explicit calculation of linear and square-root boundaries for sequential plans are given and illustrated by an example. Practical problems of applying these methods when monitoring a fixed-sample clinical trial as well as group sequential methods and calculation of P-values are also discussed.     

Active use of Cocaine: An Independent Risk Factor for Recurrent Diabetic Ketoacidosis in a City Hospital

ObjectiveTo identify the risk factors for recurrent diabetic ketoacidosis (DKA) in a city hospital.MethodsWe performed a retrospective analysis of sequential adult admissions for DKA at Bronx Lebanon Hospital Center in New York between July 1, 2001, and June 30, 2004. The patients were divided into cohorts, which were compared with use of analysis of variance and χ² tests. Multivariate logistic regression analysis was performed where indicated.ResultsIn 168 patients (96 men and 72 women), 219 episodes of DKA occurred. The mean age (± SD) of the overall study group was 38.6 ± 14.8 years. Fifty-four patients (32%) had type 2 diabetes, and 44 patients (26%) had new-onset diabetes. The recurrence rate of DKA was 169% in cocaine users and 39% in nonusers (P < 0.0001). Active use of cocaine, noncompliance, and Hispanic ethnicity emerged as independent risk factors for recurrent DKA—odds ratio (OR) = 4.38, P = 0.001; OR = 1.96, P = 0.05; and OR = 0.40, P = 0.005, respectively. The commonest precipitants of DKA were noncompliance (44%) and infection (26%). Noncompliance was associated with use of cocaine, use of cannabis, and cigarette smoking (P = 0.008, 0.04, and 0.01, respectively). In 91 of the hospital admissions for DKA (42%), the patients were active smokers.ConclusionActive use of cocaine is an independent risk factor for recurrent DKA, as are noncompliance and Hispanic ethnicity. Of these 3 factors, cocaine showed the strongest association with DKA. Therefore, toxicology screening in patients with recurrent DKA may be prudent and worthwhile. (Endocr Pract. 2007;13:22-29)     

CYP3A4 genetic variants are associated with susceptibility of non-small cell lung cancer in a Shaanxi Han population

PurposeLung cancer (LC) is one of the fastest-growing malignant tumors in the world in terms of morbidity and mortality. CYP3A4 plays a crucial role in the occurrence of LC. Little is known about the contribution of CYP3A4 polymorphisms for non-small cell lung cancer (NSCLC) risk. This study aimed to explore the correlation of CYP3A4 genetic variants (rs3735451, rs4646440, rs35564277, and rs4646437) with NSCLC risk.MethodsFour single nucleotide polymorphisms (SNPs) were genotyped by Agena MassARRAY in this case-control study (507 NSCLC patients and 505 controls) among a Shaanxi Han population. Hardy-Weinberg equilibrium (HWE) of each SNP in controls was evaluated by exact test. The association of CYP3A4 polymorphisms with NSCLC risk was explored by calculating odds ratios (OR) and 95% confidence intervals (CI) using logistic regression analysis with adjustment for age and gender.ResultsOur research revealed that rs4646440 was significantly associated with an increased risk of NSCLC (OR 2.64, p = .005), while rs4646437 played a protective role in NSCLC risk (OR 0.48, p = 4.00 × 10⁻⁷). Stratified analyses indicated that rs4646440 significantly enhanced the susceptibility of NSCLC in BMI > 24 kg/m², non-smokers and non-drinkers (OR 14.29, p = .012; OR 1.56, p = .023; OR 1.67, p = .031, respectively). Besides, we observed that rs3735451 exhibited an increased risk of NSCLC in BMI > 24 kg/m² (OR 2.47, p = .030), whereas rs4646437 had a reduced risk of NSCLC in BMI ≤ 24 kg/m² (OR 0.47, p = 5.17 × 10⁻⁵). We also found that rs35564277 was considered as a protective factor of NSCLC in non-smokers (OR 0.50, p = .032).ConclusionOur study indicated that CYP3A4 genetic variants were associated with NSCLC susceptibility in a Shaanxi Han population.     

Rheumatoid factor,not antibodies against citrullinated proteins,is associated with baseline disease activity in rheumatoid arthritis clinical trials

IntroductionAlthough the prognostic value of rheumatoid factor (RF) and autoantibodies against citrullinated proteins (ACPAs) in patients with rheumatoid arthritis (RA) is well established, their association with RA disease activity remains unclear. Here, we investigate this association in a large study using data from clinical trials.MethodsWe used baseline data from four recent randomized controlled clinical trials of RA. We investigated individual and composite measures of disease activity. The relationship of RF and ACPAs with these measures was investigated by using stratified analysis (comparing four groups of patients according to the presence or absence of RF and ACPAs) and matched analysis (disease activity levels compared between patients negative and patients highly positive for one autoantibody who were matched for levels of the other autoantibody as well as for age, gender, and duration of RA).ResultsA total of 2118 patients were analysed in the different cohorts. In the stratified analysis, RF⁺ patients, regardless of ACPA status, had the highest levels of disease activity, whereas ACPA⁺ patients had disease activity that was similar to or lower than that of ACPA⁻ patients, both in the presence and in the absence of RF. When matched for ACPA levels, patients with highly positive RF had significantly higher disease activity for all composite indices compared with patients who were RF⁻ (P = 0.0067), whereas ACPA-highly-positive and ACPA-negative patients matched for RF levels had similar disease activity, again even with the tendency toward lower disease activity for ACPA⁺ patients (P = 0.054).ConclusionThe data presented suggest that the presence of RF has a clear association with higher levels of disease activity but that the presence of ACPAs has not and even appears to be associated with lower disease activity.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0736-9) contains supplementary material, which is available to authorized users.     

11q21区段与中国汉族人群Graves病相关性研究

目的:在中国人群中验证Cooper团队在欧洲人群中鉴定的新的Graves病(Graves'disease,GD)易感区段11q21与中国汉族人群GD的相关性。方法:在前期1442例GD患者和1468例正常对照的GWAS数据基础上通过11q21区段精细定位选取主效位点,利用Taqman探针技术进行等位基因分析,在1594例GD患者和1679例正常对照中进行扩大样本验证,然后将两个阶段的结果合并分析并得出11q21区段与GD的相关性结果。结果:验证阶段11q21的rs12575636与GD相关的P值为2.98×10~(-5)(OR=1.42,95%CI=1.20-1.67),GWAS阶段和验证阶段合并后11q21的rs12575636与GD相关的P值达到1.26×10~(-6)(OR=1.35,95%CI=1.19-1.51)。结论:11q21的rs12575636与中国汉族人群GD显著相关,11q21的rs12575636是中国汉族人GD的易感位点。     

Alcohol-Related Risk of Suicidal Ideation,Suicide Attempt,and Completed Suicide: A Meta-Analysis

BackgroundSeveral original studies have investigated the effect of alcohol use disorder (AUD) on suicidal thought and behavior, but there are serious discrepancies across the studies. Thus, a systematic assessment of the association between AUD and suicide is required.MethodsWe searched PubMed, Web of Science, and Scopus until February 2015. We also searched the Psycinfo web site and journals and contacted authors. We included observational (cohort, case-control, and cross-sectional) studies addressing the association between AUD and suicide. The exposure of interest was AUD. The primary outcomes were suicidal ideation, suicide attempt, and completed suicide. We assessed heterogeneity using Q-test and I² statistic. We explored publication bias using the Egger''s and Begg''s tests and funnel plot. We meta-analyzed the data with the random-effects models. For each outcome we calculated the overall odds ratio (OR) or risk ratio (RR) with 95% confidence intervals (CI).ResultsWe included 31 out of 8548 retrieved studies, with 420,732 participants. There was a significant association between AUD and suicidal ideation (OR=1.86; 95% CI: 1.38, 2.35), suicide attempt (OR=3.13; 95% CI: 2.45, 3.81); and completed suicide (OR=2.59; 95% CI: 1.95, 3.23 and RR=1.74; 95% CI: 1.26, 2.21). There was a significant heterogeneity among the studies, but little concern to the presence of publication bias.ConclusionsThere is sufficient evidence that AUD significantly increases the risk of suicidal ideation, suicide attempt, and completed suicide. Therefore, AUD can be considered an important predictor of suicide and a great source of premature death.     

Association of Vitamin D Status With Hospital Morbidity and Mortality in Adult Hospitalized Patients With COVID-19

ObjectiveTo determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patientsMethodsWe performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality.ResultsAmong the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index <30 kg/m², vitamin D sufficiency was statistically significantly associated with a decreased odds of death (adjusted OR 0.18, 95% CI, 0.04-0.84). No significant association was found in the subgroups of patients aged <65 years or with body mass index ≥30 kg/m².ConclusionWe revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.     

Common harms from amoxicillin: a systematic review and meta-analysis of randomized placebo-controlled trials for any indication

Background:When prescribing antibiotics for common indications, clinicians need information about both harms and benefits, information that is currently available only from observational studies. We quantified the common harms of the most frequently prescribed antibiotic, amoxicillin, from randomized placebo-controlled trials.Methods:For this systematic review, we searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, without language restriction, for any randomized, participant-blinded, placebo-controlled trials of amoxicillin or amoxicillin–clavulanic acid for any indication, in any setting. Our main outcome was any reported adverse event.Results:Of 730 studies identified, we included 45 trials: 27 involving amoxicillin, 17 involving amoxicillin–clavulanic acid and 1 involving both. The indications for antibiotic therapy were variable. The risk of bias was low, although only 25 trials provided data suitable for assessment of harms, which suggested under-reporting. Diarrhea was attributed to amoxicillin only in the form of amoxicillin–clavulanic acid (Peto odds ratio [OR] 3.30, 95% confidence interval [CI] 2.23–4.87). The OR for candidiasis (3 trials) was significantly higher (OR 7.77, 95% CI 2.23–27.11). Rashes, nausea, itching, vomiting and abnormal results on liver function tests were not significantly increased. The results were not altered by sensitivity analyses, nor did funnel plots suggest publication bias. The number of courses of antibiotics needed to harm was 10 (95% CI 6–17) for diarrhea with amoxicillin–clavulanic acid and 27 (95% CI 24–42) for candidiasis with amoxicillin (with or without clavulanic acid).Interpretation:Diarrhea was caused by use of amoxicillin–clavulanic acid, and candidiasis was caused by both amoxicillin and amoxicillin–clavulanic acid. Harms were poorly reported in most trials, and their true incidence may have been higher than reported. Nevertheless, these rates of common harms associated with amoxicillin therapy may inform decisions by helping clinicians to balance harms against benefits.Most antibiotics are prescribed by primary care clinicians for common infections, particularly acute respiratory infections.¹ However, for most acute respiratory infections, antibiotics provide only marginal benefits, and an inevitable consequence of this injudicious use is the prospect of antibiotic resistance. One way to reduce antibiotic prescribing in primary care is to explain to patients how little these drugs help for many common infections and to apply a process of shared decision-making during the consultation.²The practice of shared decision-making requires not just an explanation of the paucity of benefits of antibiotics in most primary care situations, but also an explanation of the potential harms. Serious harms are probably sufficiently rare to be discounted by most clinicians and their patients.³ Yet when the decision to use or not use antibiotics relates to a self-remitting illness, for which the benefits are likely to be modest at best, the more common, mild harms of antibiotics become important. Unfortunately, common harms from antibiotics are poorly quantified, and clinicians cannot talk to patients with confidence about their likelihood.Current understanding of the common harms of antibiotics is derived largely from observational studies. However, estimates of common harms from such studies may be biased, principally because it is difficult to distinguish adverse drug reactions from disease-related symptoms. One approach to addressing this problem is to investigate common harms encountered in randomized controlled trials of antibiotic against placebo. This study design controls for disease-related symptoms, allowing for better quantification of antibiotic-related adverse effects.The most common antibiotic used in primary care is amoxicillin, either alone or in combination with clavulanic acid. “Common harms” can be defined as those frequent enough to be observable in the patient samples of most randomized trials and occurring during the recording of primary outcomes in such studies (with recognition that some of the adverse effects will occur later).Accordingly, we systematically reviewed all published placebo-controlled randomized trials of amoxicillin or amoxicillin–clavulanic acid for any indication, with the rationale that the risks of drug-induced harms are independent of the condition being treated.⁴     

Incidental Thyroid Cancer in Toxic and Nontoxic Goiter: is TSH Associated with Malignany Rate? Results of A Meta-Analysis

ObjectiveIn the last 6 years, several studies reported a positive association between thyrotropin (TSH) and papillary cancer risk. The rationale is based on stimulatory action exerted by TSH on thyroid cell proliferation and/ or progression of a pre-existing papillary carcinoma. To validate this hypothesis, we performed a meta-analysis comparing the incidence of thyroid cancer in 2 groups of patients who underwent surgery for toxic or nontoxic nodular goiter.MethodsUsing data from 2,150 patients with toxic multinodular goiter (TMNG) and 873 patients with toxic adenoma (TA), the overall incidence of thyroid cancer (and 95% confidence interval [CIs]) was estimated to be 5.9% (3.9 to 8.3) for patients with TMNG and 4.8% (2.5 to 7.9) for patients with TA. Four studies were included in the meta-analysis with a total of 1,964 subjects undergoing thyroidectomy for allegedly benign thyroid disease (520 patients with TMNG or TA and 1,444 for multinodular goiter [MNG] or uninodular goiter [UNG]).ResultsWe did not find any significant differences in the risk of incidental thyroid cancer (ITC) in patients with TMNG versus MNG (odds ratio [OR]: 0.91, 95% CI: 0.47 to 1.77, I⁴: 62.6%), TA versus uninodular goiter (UNG) (OR: 0.46, 95% CI: 0.12 to 1.79, I⁵: 12%), and TMNG or TA versus MNG or UNG (pooled analysis) (OR: 0.86, 95% CI: 0.46 to 1.60, I⁶: 51.5%).ConclusionsThe results of this meta-analysis did not confirm an association between low TSH values and lower thyroid cancer rate, at least in patients with nodular disease. (Endocr Pract. 2013;19:212-218)     

ERAP1 genetic variations associated with HLA-B27 interaction and disease severity of syndesmophytes formation in Taiwanese ankylosing spondylitis

IntroductionAnkylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese.MethodsFour ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters.ResultsThe SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10^-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10^-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10^-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10^-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10^-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10^-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P <0.00001, OR 1.38, 95% CI: 1.12 to 1.58) in Taiwanese.ConclusionsThis study provides the first evidence of ERAP1 SNPs involving syndesmophyte formation. The interactions between ERAP1 SNPs and HLA-B27 play critical roles in pMHC I pathway processing contributing to the pathogenesis of AS in multiple populations.     

Corticosteroids in the Treatment of Community-Acquired Pneumonia in Adults: A Meta-Analysis

Background

The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.

Methods

Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis.

Results

Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37–1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11–0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26–0.97; P = 0.04; I ² = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68–4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41–6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65–2.84; P = 0.41).

Conclusion

Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials.     

Robotic Assisted Radical Cystectomy with Extracorporeal Urinary Diversion Does Not Show a Benefit over Open Radical Cystectomy: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

BackgroundThe number of robotic assisted radical cystectomy (RARC) procedures is increasing despite the lack of Level I evidence showing any advantages over open radical cystectomy (ORC). However, several systematic reviews with meta-analyses including non-randomised studies, suggest an overall benefit for RARC compared to ORC. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) to evaluate the perioperative morbidity and efficacy of RARC compared to ORC in patients with bladder cancer.MethodsLiterature searches of Medline/Pubmed, Embase, Web of Science and clinicaltrials.gov databases up to 10^th March 2016 were performed. The inclusion criteria for eligible studies were RCTs which compared perioperative outcomes of ORC and RARC for bladder cancer. Primary objective was perioperative and histopathological outcomes of RARC versus ORC while the secondary objective was quality of life assessment (QoL), oncological outcomes and cost analysis.ResultsFour RCTs (from 5 articles) met the inclusion criteria, with a total of 239 patients all with extracorporeal urinary diversion. Patient demographics and clinical characteristics of RARC and ORC patients were evenly matched. There was no significant difference between groups in perioperative morbidity, length of stay, positive surgical margin, lymph node yield and positive lymph node status. RARC group had significantly lower estimated blood loss (p<0.001) and wound complications (p = 0.03) but required significantly longer operating time (p<0.001). QoL was not measured uniformly across trials and cost analysis was reported in one RCTs. A test for heterogeneity did highlight differences across operating time of trials suggesting that surgeon experience may influence outcomes.ConclusionsThis study does not provide evidence to support a benefit for RARC compared to ORC. These results may not have inference for RARC with intracorporeal urinary diversion. Well-designed trials with appropriate endpoints conducted by equally experienced ORC and RARC surgeons will be needed to address this.     

Pretreatment Predictors of Response to PegIFN-RBV Therapy in Egyptian Patients with HCV Genotype 4

BackgroundEgypt has the highest prevalence of a difficult to treat chronic hepatitis C virus (HCV), genotype 4. Pretreatment factors could guide individualization of therapy which aids in treatment optimization and interleukin IL28B gene polymorphism has been shown to closely relate to HCV treatment response. Polymorphisms in genes encoding inhibitors of T-cell response, which have role in disease progression as Programmed Cell Death 1 (PD-1), and Cytotoxic T-Lymphocytes Antigen-4 (CTLA-4), could be candidate markers predicting treatment response.MethodsThis cohort study consisted of 200 chronic HCV genotype 4 infected patients treated with PegIFN α-2a and RBV in 2 hepatology centers. Genotyping of the polymorphisms in the IL28B gene region (rs12979860), PD1.3 (rs11568821) and CTLA-4 (rs231775) was performed on DNA collected from each patient using TaqMan^® genotyping assay. Groups were classified according to response into sustained virological responders (SVR), or non-responders (NR). A multivariate logistic regression analysis was used to identify potential markers, host pretreatment clinical and viral predictive factors including viral load, insulin resistance, and alpha fetoprotein (AFP) related to treatment response.ResultsOur results showed that in a multivariate analyses IL28B C/C genotype was the most significant predictor for SVR (OR = 10.86; p<0.0001) followed by AFP (OR = 0.915; p = 0.001) then CTLA-4/G genotypes (OR = 1.948; p = 0.022). However, PD-1.3/A genotypes and platelets count were significantly related to response in univariate analysis only (OR = 1.973; p = 0.023; OR = 1.007; p = 0.009 respectively).ConclusionIL28B SNP, AFP level, and CTLA-4 SNP could be used in conjunction to predict treatment response in HCV genotype 4 infected Egyptian patients.     

An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

Background

Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs) and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (co)factors.

Methods

Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I² test. Publication bias was evaluated using Begg’s test, Egger’s test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0.

Results

A total of 14 studies (6,398 patients) met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455–36.533; P < 0.001) and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725–107.784; P < 0.001). No statistical heterogeneity was observed across studies (P = 0.819, I² = 0%; P = 0.874, I² = 0%, respectively). Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273–69.436; P<0.001).

Conclusions

Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted to examine the potential association between GBCAs other than gadodiamide and NSF.     

加味左归丸联合雌孕激素序贯治疗对早发性卵巢功能不全患者子宫动脉血流动力学、氧化应激和免疫因子的影响

摘要 目的：探讨加味左归丸联合雌孕激素序贯治疗对早发性卵巢功能不全（POI）患者子宫动脉血流动力学、氧化应激和免疫因子的影响。方法：纳入我院2019年10月-2021年10月期间收治的100例POI患者,按照随机数字表法分为对照组（雌孕激素序贯治疗,50例）和研究组（加味左归丸联合雌孕激素序贯治疗,50例）。对比两组中医证候积分、子宫动脉血流动力学、氧化应激指标、性激素指标和免疫因子指标。结果：两组治疗后月经周期、月经量、腰膝酸软、潮热盗汗、头晕耳鸣、阴道干涩、失眠多梦、五心烦热、性欲降低评分均下降,且研究组低于对照组（P<0.05）。两组治疗后子宫动脉收缩期峰值流速（Vmax）升高,搏动指数（PI）、阻力指数（RI）下降,且研究组的变化程度大于对照组（P<0.05）。两组治疗后血清丙二醛（MDA）下降,谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）升高,且研究组的变化程度大于对照组（P<0.05）。两组治疗后雌二醇（E2）升高,促黄体生成素（LH）、促卵泡生成激素（FSH）下降,且研究组的变化程度大于对照组（P<0.05）。两组治疗后NK细胞、CD8⁺下降,CD3⁺、CD4⁺、CD4⁺/CD8⁺升高,且研究组的变化程度大于对照组（P<0.05）。结论：加味左归丸联合雌孕激素序贯治疗POI患者,可有效改善子宫动脉血流动力学、性激素、氧化应激和免疫功能,促进患者恢复。     

Apport de la scintigraphie rénale dynamique au 99mTc-DTPA avec épreuve au furosémide dans l’exploration du syndrome de la jonction pyélo-urétérale a minima. À propos de 17 cas

IntroductionThe renal scintigraphy using ^99mTc-DTPA with furosemid test constitutes a noninvasive and functional method that is of appreciable interest in the exploration of the upper urinary tract and in the evaluation of the separate renal function. It distinguishes the functional character of dilation from organic obstruction needing surgery or endoscopic treatment.Material and methodsWe report, through this work, the observations of 17 patients with a low grade ureteropelvic junction syndrome detect by intravenous urography (IVU). ^99mTc-DTPA renal scintigraphy with furosemid test was carried out among all our patients by means of a gamma-camera with large field equipped with a low energy high-resolution parallel collimator. The evaluation of images obtained consisted of analysis of ureteropelvic permeability taking into account the semiquantitative parameters of time-activity curve or isotopic nephrogram (IN) obtained after digital reconstruction of sequential images.ResultsOn the 17 studied cases, the sex-ratio was equal to 1.83; the average age was 18.92 years with extremes spanning from 4 years to 70 years. Renal scintigraphy categorised four patients groups. Group I: two patients (11.76%) with normal aspect of IN; group II; seven patients (41.17% of cases) with functional dilation; groupe III: five patients (29.41%) with organic obstruction and a group IV: three patients (17.64%) with intermediate response.Discussion^99mTc-DTPA renal scintigraphy with furosemid test allowed, through our study, to obviate the limits of IVU and manometric explorations to distinguish functional dilation of organic obstruction. It permits the improvement of treatment with a favourable dosimetry.     

The efficacy and safety of intensive statin therapy: a meta-analysis of randomized trials

Background

Recent lipid guidelines recommend aggressive low-density lipoprotein (LDL) cholesterol lowering in patients with coronary artery disease. To clarify the evidence for this recommendation, we conducted a meta-analysis of randomized controlled trials that compared different intensities of statin therapy.

Methods

We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registery of Controlled Trials, Web of Science) for randomized controlled trials published up to July 19, 2007, that compared statin regimens of different intensities in adults with coronary artery disease and that reported cardiovascular events or mortality. Data were pooled using random-effects models to calculate odds ratios (OR).

Results

A total of 7 trials (29 395 patients) were included. Compared with less intensive statin regimens, more intensive regimens further reduced LDL levels (0.72 mmol/L reduction, 95% confidence interval [CI] 0.60–0.84 mmol/L), and reduced the risk of myocardial infarction (OR 0.83, 95% CI 0.77–0.91) and stroke (OR 0.82, 95% CI 0.71–0.95). Although there was no effect on mortality among patients with chronic coronary artery disease (OR 0.96, 95% CI 0.80–1.14), all-cause mortality was reduced among patients with acute coronary syndromes treated with more intensive statin regimens (OR 0.75, 95% CI 0.61–0.93). Compared with lower intensity regimens, more intensive regimens were associated with small absolute increases in rates of drug discontinuation (2.5%), elevated levels of aminotransferases (1%) and myopathy (0.5%), and there was no difference in noncardiovascular mortality. All 7 trials reported events by randomization arm rather than by LDL level achieved. About half of the patients treated with more intensive statin therapy did not achieve an LDL level of less than 2.0 mmol/L, and none of the trials tested combination therapies.

Interpretation

Our analysis supports the use of more intensive statin regimens in patients with established coronary artery disease. There is insufficient evidence to advocate treating to particular LDL targets, using combination lipid-lowering therapy to achieve these targets or for using more intensive regimens in patients without established coronary artery disease.Dyslipidemia is the most important modifiable risk factor for myocardial infarction worldwide,¹ and serum cholesterol levels are directly related to mortality from coronary artery disease in all populations studied.^2–4 Over the past decade, randomized controlled trials enrolling a wide variety of patients have confirmed that for every 1-mmol/L reduction in serum low-density lipoprotein (LDL) cholesterol achieved by statin therapy, the relative risks of cardiovascular events and mortality are reduced (by 21% and 12% respectively).⁵Statins exert their beneficial effects primarily by reducing the level of LDL cholesterol,⁶ and the reductions in the relative risk of cardiovascular events achieved by statin therapy appears to be similar regardless of baseline cholesterol levels.⁵ As a result, attention has increasingly focused on defining optimal target LDL levels, particularly in patients at highest risk (i.e., those with coronary artery disease). Based on the observational studies mentioned above,^2,3 the apparent lack of a lower threshold for statin benefit in the randomized controlled trials, and recent trials reporting greater benefits with more intensive statin regimens (compared with less intensive regimens), Canadian⁷ and American⁸ guidelines for secondary prevention now recommend target LDL levels below 2.0 mmol/L in patients with coronary artery disease. On the other hand, European guidelines specify a target LDL of 2.5 mmol/L in these patients.⁹ Questions have been raised about the safety and incremental benefits of more intensive statin regimens.^10–12We performed a systematic review and meta-analysis to critically examine the evidence for the safety, efficacy (LDL lowering) and clinical effectiveness from trials comparing more intensive statin therapy with less intensive statin therapy in patients with coronary artery disease.     

Association between Glu504Lys Polymorphism of ALDH2 Gene and Cancer Risk: A Meta-Analysis

BackgroundThe association of the aldehyde dehydrogenases-2 (ALDH2) Glu504Lys polymorphism (also named Glu487Lys, or rs671) and cancers has been investigated. This meta-analysis aims to comprehensively assess the influence of this polymorphism on the overall cancer risk.MethodsEligible publications were retrieved according to inclusion/exclusion criteria and the data were analyzed using the Review Manager software (V5.2).ResultsA meta-analysis based on 51 case-control studies consisting of 16774 cases and 32060 controls was performed to evaluate the association between the ALDH2 Glu504Lys polymorphism and cancer risk. The comparison of genotypes Lys+ (Lys/Lys and Lys/Glu) with Glu/Glu yielded a significant 20% increased cancer risk (OR = 1.20, 95%CI: 1.03–1.39, P = 0.02, I² = 92%). Subgroup analysis by cancer type indicated a significantly increased UADT cancer risk (OR = 1.39, 95%CI: 1.11–1.73, P = 0.004, I² = 94%) in individuals with the Lys+ genotypes. Subgroup analysis by country indicated that individuals from Japan with the Lys+ genotypes had a significant 38% increased cancer risk (OR = 1.38, 95%CI: 1.12–1.71, P = 0.003, I² = 93%).ConclusionsOur results indicated that the ALDH2 Glu504Lys polymorphism is a susceptible loci associated with overall cancers, especially esophageal cancer and among Japanese population.     

Bulky DNA adduct levels in normal-appearing colon mucosa,and the prevalence of colorectal adenomas

Abstract

Purpose: Examine the association between bulky DNA adduct levels in colon mucosa and colorectal adenoma prevalence, and explore the correlation between adduct levels in leukocytes and colon tissue.

Methods: Bulky DNA adduct levels were measured using ³²P-postlabelling in biopsies of normal-appearing colon tissue and blood donated by 202 patients. Multivariable logistic regression was used to examine associations between DNA adducts, and interactions of DNA adduct-DNA repair polymorphisms, with the prevalence of colorectal adenomas. Correlation between blood and tissue levels of DNA adducts was evaluated using Spearman’s correlation coefficient.

Results: An interaction between bulky DNA adduct levels and XPA rs1800975 on prevalence of colorectal adenoma was observed. Among individuals with lower DNA repair activity, increased DNA adduct levels were associated with increased colorectal adenoma prevalence (OR?=?1.41 per SD increase, 95%CI: 0.92–2.18). Conversely, among individuals with normal DNA activity, an inverse association was observed (OR?=?0.60 per SD increase, 95%CI: 0.34–1.07). Blood and colon DNA adduct levels were inversely correlated (ρ?=??0.20).

Conclusions: Among genetically susceptible individuals, higher bulky DNA adducts in the colon was associated with the prevalence of colorectal adenomas. The inverse correlation between blood and colon tissue measures demonstrates the importance of quantifying biomarkers in target tissues.