Phosphodiesterase inhibitor for heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.

Lies, damned lies and statistics: Clinical importance versus statistical significance in research.

Correctly performed and interpreted statistics play a crucial role for both those who 'produce' clinical research, and for those who 'consume' this research. Unfortunately, however, there are many misunderstandings and misinterpretations of statistics by both groups. In particular, there is a widespread lack of appreciation for the severe limitations with p values. This is a particular problem with small sample sizes and low event rates - common features of many published clinical trials. These issues have resulted in increasing numbers of false positive clinical trials (false 'discoveries'), and the well-publicised inability to replicate many of the findings. While chance clearly plays a role in these errors, many more are due to either poorly performed or badly misinterpreted statistics. Consequently, it is essential that whenever p values appear, these need be accompanied by both 95% confidence limits and effect sizes. These will enable readers to immediately assess the plausible range of results, and whether or not the effect is clinically meaningful.

Association of HLA-B27 with ankylosing spondylitis and clinical features of the HLA-B27-associated ankylosing spondylitis: a meta-analysis.

Many studies have estimated the correlation between HLA-B27 polymorphisms and ankylosing spondylitis (AS). However, the results were controversial. Therefore, we performed this meta-analysis to determine the association of HLA-B*27 polymorphisms with AS and investigate the impacts of HLA-B27 on the clinical symptoms of AS patients. A comprehensive search was performed in PubMed, Web of Science and Embase databases to retrieve the eligible studies, which addressed the association between HLA-B27 polymorphisms and AS susceptibility. The correlation in fixed-effect model was estimated using the relative risk (RR) and 95% confidence intervals (CI). Finally, 41 studies were included in this meta-analysis, among which 35 studies were used to analyze the correlation between HLA-B27 and AS. And 11 studies were applied to estimate the effects of HLA-B27 on the clinical characteristics of AS patients. Besides, our meta-analysis was composed of 8993 AS patients and 19,254 healthy controls. The results suggested that HLA-B27, HLA-B27*02 and HLA-B27*04 were positively in relation to AS (RRHLA-B27 (95% CI) 16.02 (13.85, 18.54), P < 0.001; RRHLA-B*2702 (95% CI) 1.28 (1.08, 1.53), P = 0.005; RRHLA-B27*04 (95% CI) 1.14 (1.01, 1.29), P = 0.041). Moreover, positive association was observed between HLA-B27 and sex (male) [RR (95% CI) 1.10 (1.05, 1.15), P < 0.001], family history [RR (95% CI) 1.10 (1.06, 1.140), P < 0.001], uveitis [RR (95% CI) 1.07 (1.03, 1.11), P < 0001], peripheral joint involvement [RR (95% CI) 1.04 (1.01,1.07), P = 0.013] and hip joints involvement [RR (95% CI) 1.06 (1.02, 1.10), P = 0.003]. In addition, we also found that HLA-B27*04 showed association with peripheral joint involvement [RR (95% CI) 1.13 (1.05-1.23), P = 0.002]. In conclusion, the current meta-analysis indicates that HLA-B27, especially, its subtypes (HLA-B27*02 and HLA-B27*04) may be potential risk factors for AS.

High prevalence of IgA class anti-neutrophil cytoplasmic antibodies (ANCA) is associated with increased risk of bacterial infection in patients with cirrhosis.

BACKGROUND & AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. METHODS: Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. RESULTS: Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p<0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p<0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p<0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan-Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18-2.56, p=0.006). CONCLUSIONS: Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents.

Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of cancer: a meta-analysis.

Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) on the risk of cancer have reported inconsistent results. We performed a meta-analysis of 23 eligible studies to summarize the data describing the association between cancer risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. Q-statistics and I(2) statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using a random effects model. Potential sources of heterogeneity were investigated via subgroup and sensitivity analyses, and publication biases were estimated. Overall, MCP-1 and CCR2 polymorphisms showed no significant associations with cancer risk (MCP-1-2518A/G, GG + GA vs. AA: OR=0.94, 95% CI=0.76-1.17; CCR2 V64I, AA+AG vs. GG: OR=1.27, 95% CI=0.87-1.86). However, strong evidence of heterogeneity was found among the investigated studies, and subgroup analyses were therefore conducted according to study location, cancer type, source of controls, and presence of deviation from the Hardy-Weinberg equilibrium (HWE). When the data were stratified by study location, the increased risk of cancer among A allele carriers of CCR2 V64I was observed only in studies conducted in Asian countries (AA+AG vs. GG: OR=1.65; 95% CI=1.25-2.18). This meta-analysis suggests that genetic polymorphisms of CCR2 V64I may influence the susceptibility of cancer in Asian countries. Further well-designed studies with larger sample sizes should be conducted.

Meningioma grading based on positron emission tomography: A systematic review and meta-analysis.

Introduction: Meningiomas are the most common central nervous system tumor in adults. Knowledge of the tumor grade can guide optimal treatment timing and shape personalized follow-up strategies. Positron emission tomography (PET) has been utilized for the metabolic assessment of various intracranial space-occupying lesions. Herewith, we set out to evaluate the diagnostic accuracy of PET for the noninvasive assessment of meningioma's grade. Materials and methods: The Medline, Scopus and Cochrane databases were systematically searched in March 2022 for studies that evaluated the sensitivity and specificity of PET compared to the gold standard of histological diagnosis in the grading of meningiomas. Summary statistics will be calculated and scatter plots, summary curve from the HSROC model and posterior predictions by empirical Bayes estimates will be presented. Results: Five studies consisting of 242 patients with a total of 196 low-grade (Grade 1) and 46 high grade (Grade 2/3) meningiomas were included in our analysis. Three of the included studies used 18F-FDG, one study used 18F-FLT and one used(Whiting et al., 2011) 18 F-FET as PET tracers. The pooled sensitivity was 76% (95% CI: 52%-91%) and the pooled specificity was 89% (95% CI: 83%-93%). The diagnostic odds ratio was 27.17 (95% CI: 9.22-80.06), the positive likelihood ratio was 7.18 (95% CI: 4.54-11.34) and the negative likelihood ratio was 0.26 (95% CI: 0.11-0.61). Conclusion: PET is a promising and viable option as a noninvasive imaging tool to differentiate the meningioma grades. However, currently it cannot overtake the gold standard of histological grade confirmation. More studies are required for further validation and refinement of this imaging technique and assessment of other radiotracers as well.

Longitudinal changes in employment following a diagnosis of endometriosis: Findings from an Australian cohort study.

PURPOSE: Endometriosis is a chronic inflammatory disease affecting the reproductive, gastrointestinal, and urinary systems. We examined changes in labor force participation amongst women with endometriosis following diagnosis. METHODS: We analyzed data from 4494 women born in 1973-78 from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression models with generalized estimating equations to examine changes in labor force participation amongst 468 women with surgically confirmed endometriosis, and 375 women with clinically suspected endometriosis, relative to a comparison group of 4151 women without endometriosis. RESULTS: At diagnosis, women with surgically confirmed endometriosis were somewhat more likely to be working part-time (OR 1.26, 95% CI 0.94-1.68) or unemployed (OR 1.46, 95% CI 0.96-2.23) than before diagnosis. After diagnosis, women with surgically confirmed endometriosis remained somewhat more likely to be working part-time (OR 1.26, 95% CI 0.88-1.80) but were significantly more likely to be unemployed (OR 1.85, 95% CI 1.16-2.96) than before diagnosis. Labor force participation for women with clinically suspected endometriosis did not differ from women without endometriosis at diagnosis and did not change over time. CONCLUSIONS: Women with surgically confirmed endometriosis transitioned out the labor force following diagnosis. Supportive workplace practices may help women remain in the labor force.

Diagnostic accuracy of screening algorithms to identify persons with active pulmonary tuberculosis at prison entry: protocol of a systematic review and network meta-analysis.

Prison inmates are a high-risk group for tuberculosis (TB) infection and disease due to the increasing number of vulnerable fringe groups, risk factors (e.g., alcohol and drug addictions), contagious diseases (HIV, hepatitis), and their high-risk behavior. Compared to the general population, TB incidence and prevalence rates are significantly higher among prison inmates. Early identification of potentially infectious pulmonary TB (PTB) and targeted care of sick inmates are essential to effectively control TB within the prison system. The WHO recommends combining active and passive case-finding in prisons. No study has been published comparing the broad spectrum of screening tools using a diagnostic accuracy network meta-analysis (NMA). We aim to identify the most accurate TB case-finding algorithm at prison entry that is feasible in resource-limited prisons of high-burden TB countries and ensures continuous comprehensive TB detection services in such settings. Evidence generated by this NMA can provide important decision support in selecting the most (cost-) effective algorithms for screening methods for resource-limited settings in the short, medium, and long terms.

Echocardiographic pre-pause imaging and identifying the acoustic window during CPR reduces CPR pause time during ACLS - A prospective Cohort Study.

OBJECTIVES: Pre-pause imaging during cardiopulmonary resuscitation (CPR) involves the acquisition of poor-quality, brief images immediately prior to stopping CPR to allow shorter, better-quality images during the pause. We hypothesize that pre-pause imaging is associated with a decrease in CPR pause length and shorter image acquisition time. METHODS: Prospective, interventional cohort study enrolling out-of-hospital (OOH) cardiac arrest patients. Pre-pause imaging involves pre-localizing of the approximate sonographic window during CPR to support subsequent fine tuning when CPR pauses. Physicians were educated on pre-pause imaging and data was recorded prior- and post- introduction of pre-pause imaging into American cardiac life support (ACLS). Timing of CPR pauses and identification of interventions and events during pause were recorded (e.g., intubation, defibrillation, multiple cardiac ultrasounds). Ultrasound (US) images were reviewed for image quality using a 5-point scale. Primary outcome was length of CPR pause with and without pre-pause imaging. Secondary outcome included US length. RESULTS: One hundred and forty five subjects presenting after OOH cardiac arrest were enrolled over 13 months, 70 during the baseline period prior to pre-pause imaging and 75 after pre-pause imaging was integrated into ACLS. Pre-pause imaging decreased CPR pause length from 28.3 s (95%CI 25.1-31.5) to 12.8 s (95%CI 11.9-13.7). US image acquisition time decreased with pre-pause imaging from 20.4 (95%CI 18.0-22.7) to 11.0 s (95%CI 10.1-11.8). US image quality was unchanged despite the decrease in image acquisition time. (3.0 (95%CI 2.8-3.2) vs 2.7 (95%CI 2.5-2.9)). Multivariate modeling showed that ultrasound did not prolong CPR pause length. CONCLUSION: Pre-pause imaging was associated with significant decrease in CPR pause length and US image acquisition time. Pre-pause imaging should be encouraged for any clinicians who use ultrasound during ACLS.

Development and validation of a novel image quality rating scale for echocardiography during cardiac arrest.

OBJECTIVE: Research into echocardiography (echo) during cardiac arrest has suffered from methodological flaws that limit aggregation of findings. We developed and validated a novel image rating scale for qualitative analysis of echo images obtained during resuscitation. METHODS: A novel 5-point ordinal rating scale was developed and validated using recorded echo images from 145 consecutive cardiac arrest patients. Recorded echo images were reviewed in a blinded fashion by investigators experienced in cardiac arrest echo, and image quality was rated using this scale. Cardiac activity was subsequently classified as no activity, disorganized activity and organized activity. The primary outcome was inter-rater agreement using the image quality rating scale. Secondary outcome was the qualitative evaluation of the type of cardiac activity. RESULTS: A total of 235 ultrasounds were analyzed by study investigators using the image quality rating scale. The overall image quality agreement between reviewers using the scale was good with a weighted kappa of 0.65. Agreement for image quality in subxyphoid images was greater than in parasternal images (0.65-0.52). Echo analysis of cardiac activity showed no activity (33%), disorganized activity (18%), and organized activity (49%). Agreement was great for presence or absence of "cardiac activity" and "organized cardiac activity" with a kappa of 0.84 and 0.78. CONCLUSIONS: A novel image quality rating scale for echo during cardiac arrest demonstrates substantial agreement between reviewers. Agreement regarding the presence or absence, as well as the organization of cardiac activity was substantial.

Age-Related Changes in Clinical Presentation of Covid-19: the EPICOVID19 Web-Based Survey.

BACKGROUND: The influence of aging and multimorbidity on Covid-19 clinical presentation is still unclear. OBJECTIVES: We investigated whether the association between symptoms (or cluster of symptoms) and positive SARS-CoV-2 nasopharyngeal swab (NPS) was different according to patients' age and presence of multimorbidity. METHODS: The study included 6680 participants in the EPICOVID19 web-based survey, who reported information about symptoms from February to June 2020 and who underwent at least one NPS. Symptom clusters were identified through hierarchical cluster analysis. The associations between symptoms (and clusters of symptoms) and positive NPS were investigated through multivariable binary logistic regression in the sample stratified by age (<65 vs ≥65 years) and number of chronic diseases (0 vs 1 vs ≥2). RESULTS: The direct association between taste/smell disorders and positive NPS was weaker in older and multimorbid patients than in their younger and healthier counterparts. Having reported no symptoms reduced the chance of positive NPS by 86% in younger (95%CI: 0.11-0.18), and by 46% in older participants (95%CI: 0.37-0.79). Of the four symptom clusters identified (asymptomatic, generic, flu-like, and combined generic and flu-like symptoms), those associated with a higher probability of SARS-CoV-2 infection were the flu-like for older people, and the combined generic and flu-like for the younger ones. CONCLUSIONS: Older age and pre-existing chronic diseases may influence the clinical presentation of Covid-19. Symptoms at disease onset tend to aggregate differently by age. New diagnostic algorithms considering age and chronic conditions may ease Covid-19 diagnosis and optimize health resources allocation. TRIAL REGISTRATION: NCT04471701 (ClinicalTrials.gov).

Optimisation of oral anticoagulants for patients with atrial fibrillation within 12 months after percutaneous coronary intervention: A meta-analysis and systematic review.

BACKGROUND: The optimal antithrombotic strategy, especially regarding oral anticoagulants (OACs) for atrial fibrillation (AF) patients with bleeding and thrombosis risk after percutaneous coronary intervention (PCI), remains unknown. This study explored the optimal oral anticoagulants for AF patients after PCI using a meta-analysis. METHODS: Randomised controlled trials were identified from PubMed, Embase, and the Cochrane Library through December 2020. Risk ratios, 95% confidence intervals, and random-effects models were used to compare different antithrombotic strategies through network meta-analysis, and the combination of antithrombotic agents was ranked according to the surface under the cumulative ranking curve and rankograms. Interval plots were drawn to observe pairwise comparisons between the different strategies. RESULTS: Five studies of 11,532 patients were included. Factor IIa inhibitor 110 mg bid plus a P2Y12 inhibitor had the greatest advantage for reducing Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding; Factor Xa inhibitor plus a P2Y12 inhibitor had the greatest advantage for reducing International Society on Thrombosis and Hemostasis major bleeding. For patients at risk of stroke plus all-cause death, factor IIa inhibitor 150 mg bid plus a P2Y12 inhibitor should be prioritised, and for those at risk of myocardial infarction and stent thrombosis, vitamin K antagonists plus a P2Y12 inhibitor were preferred. CONCLUSION: Factor IIa inhibitor 110 mg, factor IIa inhibitor 150 mg, factor Xa inhibitor and vitamin K antagonists should be selected in different situations.

Involvement of INF-γ functional single nucleotide polymorphism +874 T/A (rs2430561) in breast cancer risk.

According Global Cancer Statistics 2020 GLOBOCAN estimates female breast cancer was found as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), and the fourth leading cause (6.9%) of cancer death among women worldwide. Identification of new diagnostic marker sharply characterize the tumor feature is intensive need. The present work was performed to investigate the involvement of the INF-γ + 874 T/A gene polymorphism in different breast cancer prognostic factors. Polymorphism detection analysis was performed on 163 subjects from breast cancer patients, 79 with inflamed cells of breast patients and 144 controls. The gene polymorphism was detected using the amplification refractory mutation system- polymerase chain reaction method (ARMS-PCR). The distribution of INF-γ T + 874A gene polymorphism shows strong significant association between INF-γ + 874 T/A genotypes TT in BC patients (ORTT: 6.41 [95% CI = 2.72-15.1] P < 0.0001) as well as strong significant association regarding T allele (ORT: 1.99 [95% CI = 1.43-2.76] P < 0.0001) when compared to the healthy control. In ICB group the strong association was noted with INF-γ + 874 T/A genotypes AT genotype (ORAT: 2.28 [95% CI = 1.22-4.29] P = 0.007). From the different histological BC hormonal markers the human epidermal growth factor receptor 2 (HER2) was showing significant association in INF-γ + 874 T/A genotypes TT (P = 0.03) and recessive model (TT versus AA + AT P = 0.03). Concerning different BC prognostic models, the poor prognostic one of luminal B, (ER+ve PR+ve Her2+ve) show significant association in the host INF-γ + 874 T/A genotype (TT, P = 0.03) and recessive model (TT versus AA + AT P = 0.02) when compared to the good prognostic hormonal status luminal A model, (ER+ve PR+ve Her2-ve). It seems that this is the first study that interested in correlate the INF-γ + 874 T/A gene polymorphisms in Egyptian BC patients. T allele, TT genotype and recessive model of the INF-γ + 874 T/A gene variants were documented as risk factors for BC pathogenesis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.

Assessment of the Link of ABCB1 and NR3C1 gene polymorphisms with the prednisolone resistance in pediatric nephrotic syndrome patients of Bangladesh: A genotype and haplotype approach.

Introduction: Nephrotic syndrome is a common pediatric kidney disease. Investigations on several genetic polymorphisms revealed an inconsistent influence on the resistance of patients to steroids. Objectives: This study aimed to identify the association of ABCB1 (1236C > T, 2677G > T, 3435C > T), NR3C1 (rs10482634, rs6877893), and CYP3A5 (CYP3A5*3) gene polymorphism as well as sociodemographic and clinicopathological parameters with the risk of developing prednisolone resistance in pediatric patients with nephrotic syndrome. Methods: A case-control analysis was performed on 180 nephrotic syndrome patients. Among them, 30 patients were classified as prednisolone resistant group, and 150 were classified as prednisolone sensitive group. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: No significant association of 1236C > T polymorphism with the risk of prednisolone resistance (p > 0.05) was found. The GT heterozygous of 2677G > T was found to be significantly associated with the development of prednisolone resistance (OR = 3.9, p = 0.034). In the case of 3435C > T, a statistically significant association was observed in TC heterozygous and TT mutant homozygous genotypes (OR = 0.38, p = 0.047; OR = 3.06, p = 0.038, respectively) with prednisolone resistance. For rs10482634 polymorphism, the AG heterozygous and AG+GG genotypes were significantly linked with prednisolone resistance (OR = 2.40, p = 0.033; OR = 2.36, p = 0.034, respectively). We found no association with the risk of prednisolone resistance with rs6877893 and CYP3A5*3 polymorphism (p > 0.05). CTC and TGT haplotypes of ABCB1 and GA haplotype of NR3C1 were also associated with the increased risk of pediatric prednisolone resistance (OR = 4.47, p = 0.0003; OR = 2.71, p = 0.03; and OR = 4.22, p = 0.022, consecutively). We also observed the correlation of different sociodemographic and clinicopathological factors with prednisolone resistance in pediatric nephrotic syndrome. Conclusion: Our findings showed a significant association of ABCB1 and NR3C1 gene polymorphisms with prednisolone resistant pediatric nephrotic syndrome.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

Simulating galactic cosmic ray effects: Synergy modeling of murine tumor prevalence after exposure to two one-ion beams in rapid sequence.

Health risks from galactic cosmic rays (GCR) in space travel above low earth orbit remain a concern. For many years accelerator experiments investigating space radiation induced prevalence of murine Harderian gland (HG) tumorigenesis have been performed to help estimate GCR risks. Most studies used acute, relatively low fluence, exposures. Results on a broad spectrum of individual ions and linear energy transfers (LETs) have become available. However, in space, the crew are exposed simultaneously to many different GCR. Recent upgrades at the Brookhaven NASA Space Radiation Laboratory (NSRL) now allow mixtures in the form of different one-ion beams delivered in rapid sequence. This paper uses the results of three two-ion mixture experiments to illustrate conceptual, mathematical, computational, and statistical aspects of synergy analyses and also acts as an interim report on the mixture experiments' results. The results were interpreted using the following: (a) accumulated data from HG one-ion accelerator experiments; (b) incremental effect additivity synergy theory rather than simple effect additivity synergy theory; (c) parsimonious models for one-ion dose-effect relations; and (d), computer-implemented numerical methods encapsulated in freely available open source customized software. The main conclusions are the following. As yet, the murine HG tumorigenesis experimental studies show synergy in only one case out of three. Moreover, some theoretical arguments suggest GCR-simulating mixed beams are not likely to be synergistic. However, more studies relevant to possible synergy are needed by various groups that are studying various endpoints. Especially important is the possibility of synergy among high-LET radiations, since individual high-LET ions have large relative biological effectiveness for many endpoints. Selected terminology, symbols, and abbreviations. DER - dose-effect relation; E(d) - DER of a one-ion beam, where d is dose; HG prevalence p - in this paper, p is the number of mice with at least one Harderian gland tumor divided by the number of mice that are at risk of developing Harderian gland tumors (so that in this paper prevalence p can never, conceptually speaking, be greater than 1); IEA - incremental effect additivity synergy theory; synergy level - a specification, exemplified in Fig. 5, of how clear-cut an observed synergy is; mixmix principle - a consistency condition on a synergy theory which insures that the synergy theory treats mixtures of agent mixtures in a mathematically self-consistent way; NTE - non-targeted effect(s); NSNA - neither synergy nor antagonism; SEA - simple effect additivity synergy theory; TE - targeted effect(s); ß* - ion speed relative to the speed of light, with 0 < ß* < 1; SLI - swift light ion(s).

Dynamics of the serologic response in vaccinated and unvaccinated mumps cases during an epidemic.

In the last decade, several mumps outbreaks were reported in various countries despite high vaccination coverage. In most cases, young adults were affected who have acquired immunity against mumps solely by vaccination and not by previous wild-type mumps virus infection. To investigate mumps-specific antibody levels, functionality and dynamics during a mumps epidemic, blood samples were obtained longitudinally from 23 clinical mumps cases, with or without a prior history of vaccination, and from 20 healthy persons with no serological evidence of recent mumps virus infection. Blood samples from mumps cases were taken 1-2 months and 7-10 months after onset of disease. Both vaccinated and unvaccinated mumps cases had significantly higher geomean concentrations of mumps-specific IgG (resp. 13,617 RU/ml (95% CI of 9,574-19,367 RU/ml) vs. 1,552 (445-5412) RU/ml at 1-2 months; and 6,514 (5,247-8,088) RU/ml vs. 1,143 (480-2,725) RU/ml at 7-10 months) than healthy controls (169 (135-210) RU/ml) (p = 0.001). Patterns in virus-neutralizing (VN) antibody responses against the mumps vaccine virus were similar, vaccinated and unvaccinated mumps cases had significantly higher ND50 values at both time points of sampling (resp 4,695 (3,779-5,832) RU/ml vs. 1,533 (832-2,825) RU/ml at 1-2 months; 2,478 (1,968-3,122) RU/ml vs. 1,221 (1,029-1,449) RU/ml at 7-10 months) compared with (previously vaccinated) healthy controls (122 (196-76)) RU/ml) (p = 0.001) The unvaccinated mumps cases had significantly lower mumps-specific IgG and VN antibody concentrations at both sampling points compared with previously vaccinated cases, but their antibody concentrations did not differ significantly at the 2 time points. In contrast, the mumps-specific IgG and VN antibody concentrations of the previously vaccinated mumps cases were significantly higher within the first 2 months after onset of mumps and declined thereafter, characteristic for a secondary response. A moderate correlation was found between the level of mumps-specific IgG serum antibodies and VN antibodies for the mumps cases (r = 0.64; p<0.001).

Deviations from venous blood specimen collection guideline adherence among senior nursing students.

BACKGROUND: Despite considerable efforts to increase patient safety by supporting the use of best practice medical and nursing guidelines by healthcare staff, adherence is often suboptimal. Swedish nurses often deviate from venous blood specimen collection (VBSC) guideline adherence. We assessed the adherence to national VBSC guidelines among senior nursing students. METHODS: We conducted a cross-sectional, self-reported questionnaire survey among 101 out of 177 senior nursing students consisting of web-based students in their fifth semester and campus-based students in their fifth or sixth semester out of six. In regard to the VBSC procedures, we asked about adherence to the patient identification, test request handling, and test tube labelling protocols that the students had learned during their second semester and practiced thereafter. RESULTS: Guideline adherence to patient identification was reported by 81%, test request handling by 74%, and test tube labelling by 2% of the students. Students with no prior healthcare education reported to a higher extent that they operated within the guidelines regarding labelling the test tube before entering the patient's room compared to students with prior healthcare education. Using multiple logistic regression analysis, we found that fifth semester web-based program students adhered better to VBSC guidelines regarding comparing patient ID/test request/tube label compared to campus-based students. CONCLUSIONS: Senior nursing students were found to adhere to VBSC guidelines to a similar extent as registered nurses and other hospital ward staff in clinical healthcare. Thus student adherence to VBSC guidelines had deteriorated since their basic training in the second semester, and this can impact patient safety during university/clinical studies. The results of our study have implications for nursing practice education.

Association of glutathione S-transferase M1/T1 polymorphisms with susceptibility to vitiligo.

BACKGROUND: Some studies suggested that Glutathione S-transferases M1/T1(GSTM1/T1) null polymorphisms may be associated with the risk of vitiligo. AIMS: The purpose of this study is to further evaluate the association between GSTM1/T1 null polymorphisms and the susceptibility to vitiligo. METHODS: We carried out a retrieval of studies in the databases. Odds ratios (OR) and 95% confidence intervals (95% CIs) were used to assess the strength of this association. We analyzed the data using Stata 11.0. RESULTS: Six case-control studies including 1358 cases and 1673 controls were included in this meta-analysis. Our overall results showed the GSTM1 or GSTT1 null polymorphism was associated with vitiligo (GSTM1:OR=1.59, 95% CI: 1.21-2.08, P=0.001; GSTT1: OR=1.30, 95% CI: 1.12-1.51, P=0.001). In the subgroup analysis, the GSTM1 null polymorphism might be a genetic risk factor to vitiligo in East Asian (OR=1.71, 95% CI: 1.12-2.63, P=0.014) but not in the Mediterranean, however individuals with the GSTT1 null polymorphism in the Mediterranean (OR=1.76, 95% CI: 1.15-2.71, P=0.010) but not in East Asian have a greater predisposition to vitiligo. In addition there was also a significant trend toward an association with the combination of the GSTM1 null and GSTT1 null in either East Asians or Mediterraneans. CONCLUSION: The GSTM1/T1 null polymorphisms may be associated with vitiligo. More studies are needed to confirm this conclusion.

LINE-1 methylation in granulocyte DNA and trihalomethane exposure is associated with bladder cancer risk.

DNA methylation changes contribute to bladder carcinogenesis. Trihalomethanes (THM), a class of disinfection by-products, are associated with increased urothelial bladder cancer (UBC) risk. THM exposure in animal models produces DNA hypomethylation. We evaluated the relationship of LINE-1 5-methylcytosine levels (LINE-1%5mC) as outcome of long-term THM exposure among controls and as an effect modifier in the association between THM exposure and UBC risk. We used a case-control study of UBC conducted in Spain. We obtained personal lifetime residential THM levels and measured LINE-1%5mC by pyrosequencing in granulocyte DNA from blood samples in 548 incident cases and 559 hospital controls. Two LINE-1%5mC clusters (above and below 64%) were identified through unsupervised hierarchical cluster analysis. The association between THM levels and LINE-1%5mC was evaluated with ß regression analyses and logistic regression was used to estimate odds ratios (OR) adjusting for covariables. LINE-1%5mC change between percentiles 75(th) and 25(th) of THM levels was 1.8% (95% confidence interval (CI): 0.1, 3.4%) among controls. THM levels above vs. below the median (26 µg/L) were associated with increased UBC risk, OR = 1.86 (95% CI: 1.25, 2.75), overall and among subjects with low levels of LINE-1%5mC (n = 975), OR = 2.14 (95% CI: 1.39, 3.30), but not associated with UBC risk among subjects' high levels of LINE-1%5mC (n = 162), interaction P = 0.03. Results suggest a positive association between LINE-1%5mC and THM levels among controls, and LINE-1%5mC status may modify the association between UBC risk and THM exposure. Because reverse causation and chance cannot be ruled out, confirmation studies are warranted.