A new approach to dengue fatal cases diagnosis: NS1 antigen capture in tissues

Abstract/Background

Dengue is the most important arthropod borne viral disease worldwide in terms of morbidity and mortality and is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Brazil is responsible for approximately 80% of dengue cases in the Americas, and since the introduction of dengue in 1986, a total of 5,944,270 cases have been reported including 21,596 dengue hemorrhagic fever and 874 fatal cases. DENV can infect many cell types and cause diverse clinical and pathological effects. The goal of the study was to investigate the usefulness of NS1 capture tests as an alternative tool to detect DENV in tissue specimens from previously confirmed dengue fatal cases (n = 23) that occurred in 2002 in Brazil.

Methodology/Principal Findings

A total of 74 tissue specimens were available: liver (n = 23), lung (n = 14), kidney (n = 04), brain (n = 10), heart (n = 02), skin (n = 01), spleen (n = 15), thymus (n = 03) and lymph nodes (n = 02). We evaluated three tests for NS1 antigen capture: first generation Dengue Early ELISA (PanBio Diagnostics), Platelia NS1 (BioRad Laboratories) and the rapid test NS1 Ag Strip (BioRad Laboratories). The overall dengue fatal case diagnosis based on the tissues analyzed by Dengue Early ELISA, Platelia NS1 and the NS1 Ag Strip was 34.7% (08/23), 60.8% (14/23) and 91.3% (21/23), respectively. The Dengue Early ELISA detected NS1 in 22.9% (17/74) of the specimens analyzed and the Platelia NS1 in 45.9% (34/74). The highest sensitivity (78.3%; 58/74) was achieved by the NS1 Ag Strip, and the differences in the sensitivities were statistically significant (p<0.05). The NS1 Ag Strip was the most sensitive in liver (91.3%; 21/23), lung (71.4%; 10/14), kidney (100%; 4/4), brain (80%; 8/10), spleen (66.6%, 10/15) and thymus (100%, 3/3) when compared to the other two ELISA assays.

Conclusions/Significance

This study shows the DENV NS1 capture assay as a rapid and valuable approach to postmortem dengue confirmation. With an increasing number of DHF and fatal cases, the availability of new approaches useful for cases confirmation plays an important tool for the disease surveillance.     

Antibody-mediated growth inhibition of Plasmodium falciparum: relationship to age and protection from parasitemia in Kenyan children and adults

Background

Antibodies that impair Plasmodium falciparum merozoite invasion and intraerythrocytic development are one of several mechanisms that mediate naturally acquired immunity to malaria. Attempts to correlate anti-malaria antibodies with risk of infection and morbidity have yielded inconsistent results. Growth inhibition assays (GIA) offer a convenient method to quantify functional antibody activity against blood stage malaria.

Methods

A treatment-time-to-infection study was conducted over 12-weeks in a malaria holoendemic area of Kenya. Plasma collected from healthy individuals (98 children and 99 adults) before artemether-lumefantrine treatment was tested by GIA in three separate laboratories.

Results

Median GIA levels varied with P. falciparum line (D10, 8.8%; 3D7, 34.9%; FVO, 51.4% inhibition). The magnitude of growth inhibition decreased with age in all P. falciparum lines tested with the highest median levels among children <4 years compared to adults (e.g. 3D7, 45.4% vs. 30.0% respectively, p = 0.0003). Time-to-infection measured by weekly blood smears was significantly associated with level of GIA controlling for age. Upper quartile inhibition activity was associated with less risk of infection compared to individuals with lower levels (e.g. 3D7, hazard ratio = 1.535, 95% CI = 1.012–2.329; p = 0.0438). Various GIA methodologies had little effect on measured parasite growth inhibition.

Conclusion

Plasma antibody-mediated growth inhibition of blood stage P. falciparum decreases with age in residents of a malaria holoendemic area. Growth inhibition assay may be a useful surrogate of protection against infection when outcome is controlled for age.     

Serum cholesterol and the progression of Parkinson's disease: results from DATATOP

Background

Recent studies have suggested that higher serum cholesterol may be associated with lower occurrence of Parkinson''s disease (PD). This study is to test the hypothesis that higher serum cholesterol correlates with slower PD progression.

Methods

Baseline non-fasting serum total cholesterol was measured in 774 of the 800 subjects with early PD enrolled between 1987 and 1988 in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial. Participants were followed for up to two years, with clinical disability requiring levodopa therapy as the primary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CI) were determined for increasing serum cholesterol concentration (in quintiles) for clinical disability requiring levodopa therapy, after adjusting for confounders. At baseline, only nine subjects reported use of cholesterol-lowering agents (two with statins).

Results

The overall mean cholesterol level was 216 mg/dL (range 100–355). The HR of progressing to the primary endpoint decreased with increasing serum cholesterol concentrations. Compared to the lowest quintile, the HRs (95%CI), for each higher quintile (in ascending order) are 0.83 (0.59–1.16); 0.86 (0.61–1.20); 0.84 (0.60–1.18); and 0.75 (0.52–1.09). The HR for one standard deviation (SD) increase = 0.90 [(0.80–1.01), p for trend = 0.09]. This trend was found in males (HR per SD = 0.88 [(0.77–1.00), p for trend = 0.05], but not in females [HR = 1.03 (0.81–1.32)].

Conclusions

This secondary analysis of the DATATOP trial provides preliminary evidence that higher total serum cholesterol concentrations may be associated with a modest slower clinical progression of PD, and this preliminary finding needs confirmation from larger prospective studies.     

Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis

Background

Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), and multiple sclerosis (MS).

Objectives

To investigate comparative brain stem lesions on magnetic resonance imaging (MRI) among adult patients with ADEM, NMO, and MS.

Methods

Sixty-five adult patients with ADEM (n = 17), NMO (n = 23), and MS (n = 25) who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed.

Results

Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001) and MS (94.1% vs. 40.0%, P<0.001); patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001) and ADEM (34.8% vs. 70.6%, P = 0.025); and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001) and MS (91.3% vs. 36.0%, P<0.001). On the axial section of the brain stem, the majority (82.4%) of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%); and lesions in patients with MS were found in both the ventral (44.0%) and dorsal (56.0%) parts. The lesions in patients with ADEM (100%) and NMO (91.3%) had poorly defined margins, while lesions of patients with MS (76.0%) had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%), while lesions in patients with NMO (87.0%) and MS (92.0%) were asymmetrical or unilateral.

Conclusions

Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.     

Effect on adherence to nicotine replacement therapy of informing smokers their dose is determined by their genotype: a randomised controlled trial

Background

The behavioural impact of pharmacogenomics is untested. We tested two hypotheses concerning the behavioural impact of informing smokers their oral dose of NRT is tailored to analysis of DNA.

Methods and Findings

We conducted an RCT with smokers in smoking cessation clinics (N = 633). In combination with NRT patch, participants were informed that their doses of oral NRT were based either on their mu-opioid receptor (OPRM1) genotype, or their nicotine dependence questionnaire score (phenotype). The proportion of prescribed NRT consumed in the first 28 days following quitting was not significantly different between groups: (68.5% of prescribed NRT consumed in genotype vs 63.6%, phenotype group, difference  =  5.0%, 95% CI −0.9,10.8, p  =  0.098). Motivation to make another quit attempt among those (n  =  331) not abstinent at six months was not significantly different between groups (p  =  0.23). Abstinence at 28 days was not different between groups (p = 0.67); at six months was greater in genotype than phenotype group (13.7% vs 7.9%, difference  =  5.8%, 95% CI 1.0,10.7, p  =  0.018).

Conclusions

Informing smokers their oral dose of NRT was tailored to genotype not phenotype had a small, statistically non-significant effect on 28-day adherence to NRT. Among those still smoking at six months, there was no evidence that saying NRT was tailored to genotype adversely affected motivation to make another quit attempt. Higher abstinence rate at six months in the genotype arm requires investigation.

Trial registration

Controlled-Trials.com ISRCTN14352545.     

The effectiveness of online cognitive behavioral treatment in routine clinical practice

Context

Randomized controlled trails have identified online cognitive behavioral therapy as an efficacious intervention in the management of common mental health disorders.

Objective

To assess the effectiveness of online CBT for different mental disorders in routine clinical practice.

Design

An uncontrolled before-after study, with measurements at baseline, posttest, 6-week follow-up, and 1-year follow-up.

Participants & Setting

1500 adult patients (female: 67%; mean age: 40 years) with a GP referral for psychotherapy were treated at a Dutch online mental health clinic for symptoms of depression (n = 413), panic disorder (n = 139), posttraumatic stress (n = 478), or burnout (n = 470).

Interventions

Manualized, web-based, therapist-assisted CBT, of which the efficacy was previously demonstrated in a series of controlled trials. Standardized duration of treatment varied from 5 weeks (online CBT for Posttraumatic stress) to 16 weeks (online CBT for Depression).

Main Outcome Measures

Validated self-report questionnaires of specific and general psychopathology, including the Beck Depression Inventory, the Impact of Event Scale, the Panic Disorder Severity Scale-Self Report, the Oldenburg Burnout Inventory, and the Depression Anxiety Stress Scales.

Results

Treatment adherence was 71% (n = 1071). Study attrition was 21% at posttest, 33% at 6-week FU and 65% at 1-year FU. Mixed-model repeated measures regression identified large short-term reductions in all measures of primary symptoms (d = 1.9±0.2 to d = 1.2±0.2; P<.001), which sustained up to one year after treatment. At posttest, rates of reliable improvement and recovery were 71% and 52% in the completer sample (full sample: 55%/40%). Patient satisfaction was high.

Conclusions

Results suggest that online therapist-assisted CBT may be as effective in routine practice as it is in clinical trials. Although pre-treatment withdrawal and long-term outcomes require further study, results warrant continued implementation of online CBT.     

Effect of an injury awareness education program on risk-taking behaviors and injuries in juvenile justice offenders: a retrospective cohort study

Background

Risk-taking behavior is a leading cause of injury and death amongst young people.

Methodology and Principal Findings

This was a retrospective cohort study on the effectiveness of a 1-day youth injury awareness education program (Prevent Alcohol and Risk-related Trauma in Youth, P.A.R.T.Y.) program in reducing risk taking behaviors and injuries of juvenille justice offenders in Western Australia. Of the 3659 juvenile justice offenders convicted by the court magistrates between 2006 and 2010, 225 were referred to the P.A.R.T.Y. education program. In a before and after survey of these 225 participants, a significant proportion of them stated that they were more receptive to modifying their risk-taking behavior (21% before vs. 57% after). Using data from the Western Australia Police and Department of Health, the incidence of subsequent offences and injuries of all juvenile justice offenders was assessed. The incidence of subsequent traffic or violence-related offences was significantly lower for those who had attended the program compared to those who did not (3.6% vs. 26.8%; absolute risk reduction [ARR] = 23.2%, 95% confidence interval [CI] 19.9%–25.8%; number needed to benefit = 4.3, 95%CI 3.9–5.1; p = 0.001), as were injuries leading to hospitalization (0% vs. 1.6% including 0.2% fatality; ARR = 1.6%, 95%CI 1.2%–2.1%) and alcohol or drug-related offences (0% vs. 2.4%; ARR 2.4%, 95%CI 1.9%–2.9%). In the multivariate analysis, only P.A.R.T.Y. education program attendance (odds ratio [OR] 0.10, 95%CI 0.05–0.21) and a higher socioeconomic background (OR 0.97 per decile increment in Index of Relative Socioeconomic Advantage and Disadvantage, 95%CI 0.93–0.99) were associated with a lower risk of subsequent traffic or violence-related offences.

Significance

Participation in an injury education program involving real-life trauma scenarios was associated with a reduced subsequent risk of committing violence- or traffic-related offences, injuries, and death for juvenille justice offenders.     

Malaria case-management following change of policy to universal parasitological diagnosis and targeted artemisinin-based combination therapy in Kenya

Background

The change of malaria case-management policy in Kenya to recommend universal parasitological diagnosis and targeted treatment with artemether-lumefantrine (AL) is supported with activities aiming by 2013 at universal coverage and adherence to the recommendations. We evaluated changes in health systems and case-management indicators between the baseline survey undertaken before implementation of the policy and the follow-up survey following the first year of the implementation activities.

Methods/Findings

National, cross-sectional surveys using quality-of-care methods were undertaken at public facilities. Baseline and follow-up surveys respectively included 174 and 176 facilities, 224 and 237 health workers, and 2,405 and 1,456 febrile patients. Health systems indicators showed variable changes between surveys: AL stock-out (27% to 21%; p = 0.152); availability of diagnostics (55% to 58%; p = 0.600); training on the new policy (0 to 22%; p = 0.001); exposure to supervision (18% to 13%; p = 0.156) and access to guidelines (0 to 6%; p = 0.001). At all facilities, there was an increase among patients tested for malaria (24% vs 31%; p = 0.090) and those who were both tested and treated according to test result (16% to 22%; p = 0.048). At facilities with AL and malaria diagnostics, testing increased from 43% to 50% (p = 0.196) while patients who were both, tested and treated according to test result, increased from 28% to 36% (p = 0.114). Treatment adherence improved for test positive patients from 83% to 90% (p = 0.150) and for test negative patients from 47% to 56% (p = 0.227). No association was found between testing and exposure to training, supervision and guidelines, however, testing was significantly associated with facility ownership, type of testing, and patients'' caseload, age and clinical presentation.

Conclusions

Most of the case-management indicators have shown some improvement trends; however differences were smaller than expected, rarely statistically significant and still leaving a substantial gap towards optimistic targets. The quantitative and qualitative improvement of interventions will ultimately determine the success of the new policy.     

Tumor necrosis factor-alpha g308α gene polymorphism and essential hypertension: a meta-analysis involving 2244 participants

Background

The tumor necrosis factor-alpha (TNFα) G308A gene polymorphism has been implicated in susceptibility to essential hypertension (EH), but study results are still controversial.

Objective and Methods

The present meta-analysis is performed to investigate the relationship between the TNFα G308A gene polymorphism and EH. Electronic databases were searched and seven separate studies on the association of the TNF α G308A gene polymorphism with EH were analyzed. The meta-analysis involved 1092 EH patients and 1152 controls. The pooled odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated by a fixed or random effect model.

Results

A significant relationship between the TNFα G308A gene polymorphism and EH was found in an allelic genetic model (OR: 1.45, 95% CI: 1.17 to 1.80, P = 0.0008), a recessive genetic model (OR: 3.181, 95% CI: 1.204 to 8.408, P = 0.02), and a homozygote model (OR: 3.454, 95% CI: 1.286 to 9.278, P = 0.014). No significant association between them was detected in both a dominant genetic model (OR: 1.55, 95% CI: 0.99 to 2.42, P = 0.06) or a heterozygote genetic model (OR: 1.45, 95% CI: 0.90 to 2.33, P = 0.13).

Conclusion

The TNFα G308A gene polymorphism is associated with EH susceptibility.     

Thoracic empyema: a 12-year study from a UK tertiary cardiothoracic referral centre

Background

Empyema is an increasingly frequent clinical problem worldwide, and has substantial morbidity and mortality. Our objectives were to identify the clinical, surgical and microbiological features, and management outcomes, of empyema.

Methods

A retrospective observational study over 12 years (1999–2010) was carried out at The Heart Hospital, London, United Kingdom. Patients with empyema were identified by screening the hospital electronic ‘Clinical Data Repository’. Demographics, clinical and microbiological characteristics, underlying risk factors, peri-operative blood tests, treatment and outcomes were identified. Univariable and multivariable statistical analyses were performed.

Results

Patients (n = 406) were predominantly male (74.1%); median age = 53 years (IQR = 37–69). Most empyema were community-acquired (87.4%) and right-sided (57.4%). Microbiological diagnosis was obtained in 229 (56.4%) patients, and included streptococci (16.3%), staphylococci (15.5%), Gram-negative organisms (8.9%), anaerobes (5.7%), pseudomonads (4.4%) and mycobacteria (9.1%); 8.4% were polymicrobial. Most (68%) cases were managed by open thoracotomy and decortication. Video-assisted thoracoscopic surgery (VATS) reduced hospitalisation from 10 to seven days (P = 0.0005). All-cause complication rate was 25.1%, and 28 day mortality 5.7%. Predictors of early mortality included: older age (P = 0.006), major co-morbidity (P = 0.01), malnutrition (P = 0.001), elevated red cell distribution width (RDW, P<0.001) and serum alkaline phosphatase (P = 0.004), and reduced serum albumin (P = 0.01) and haemoglobin (P = 0.04).

Conclusions

Empyema remains an important cause of morbidity and hospital admissions. Microbiological diagnosis was only achieved in just over 50% of cases, and tuberculosis is a notable causative organism. Treatment of empyema with VATS may reduce duration of hospital stay. Raised RDW appears to associate with early mortality.     

Associations between XPD Asp312Asn polymorphism and risk of head and neck cancer: a meta-analysis based on 7,122 subjects

Background

To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.

Methods

We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.

Results

Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P _{heterogeneity} = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P _{heterogeneity} = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P _{heterogeneity} = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P _{heterogeneity} = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.

Conclusions

This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.     

Molecular analysis and risk factors for Escherichia coli producing extended-spectrum β-lactamase bloodstream infection in hematological malignancies

Introduction

Patients with hematologic malignancies have greater risk-factors for primary bloodstream infections (BSI).

Methods

From 2004–2009, we analyzed bacteremia caused by extended-spectrum beta-lactamase Escherichia coli (ESBL-EC) (n = 100) and we compared with bacteremia caused by cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies.

Objective

To assess the clinical features, risk factors, and outcome of ESBL-EC BSI in patients with hematologic malignancies, and to study the molecular epidemiology of ESBL-EC isolates.

Results

The main diagnosis was acute leukemia in 115 patients (57.5%). Death-related E. coli infection was significantly increased with ESBL-EC (34% vs. control group, 19%; p = 0.03). Treatment for BSI was considered appropriate in 64 patients with ESBL-EC (mean survival, 245±345 days), and in 45 control patients this was 443±613 (p = 0.03). In patients not receiving appropriate antimicrobial treatment, survival was significantly decreased in cases compared with controls (26±122 vs. 276±442; p = 0.001). Fifty six of the ESBL-EC isolates were characterized by molecular analysis: 47 (84%) expressed CTX-M-15, two (3.6%) SHV, and seven (12.5%) did not correspond to either of these two ESBL enzymes. No TLA-1 enzyme was detected.

Conclusions

Patients who had been previously hospitalized and who received cephalosporins during the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected, which reflects non-cross transmission of multiresistant E.coli isolates.     

The -675 4G/5G polymorphism in plasminogen activator inhibitor-1 gene is associated with risk of asthma: a meta-analysis

Background

A number of studies assessed the association of −675 4G/5G polymorphism in the promoter region of plasminogen activator inhibitor (PAI)-1 gene with asthma in different populations. However, most studies reported inconclusive results. A meta-analysis was conducted to investigate the association between polymorphism in the PAI-1 gene and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, HuGE Literature Finder, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the dominant model, recessive model, codominant model, and additive model.

Results

Eight studies involving 1817 cases and 2327 controls were included. Overall, significant association between 4G/5G polymorphism and asthma susceptibility was observed for 4G4G+4G5G vs. 5G5G (OR = 1.56, 95% CI 1.12–2.18, P = 0.008), 4G/4G vs. 4G/5G+5G/5G (OR = 1.38, 95% CI 1.06–1.80, P = 0.02), 4G/4G vs. 5G/5G (OR = 1.80, 95% CI 1.17–2.76, P = 0.007), 4G/5G vs. 5G/5G (OR = 1.40, 95% CI 1.07–1.84, P = 0.02), and 4G vs. 5G (OR = 1.35, 95% CI 1.08–1.68, P = 0.008).

Conclusions

This meta-analysis suggested that the −675 4G/5G polymorphism of PAI-1 gene was a risk factor of asthma.     

Ziehl-Neelsen staining technique can diagnose paragonimiasis

Background

We evaluated the Ziehl-Neelsen staining (ZNS) technique for the diagnosis of paragonimiasis in Laos and compared different modifications of the ZNS techniques.

Methodology

We applied the following approach: We (1) examined a paragonimiasis index case''s sputum with wet film direct examination (WF) and ZNS; (2) re-examined stored ZNS slides from two provinces; (3) compared prospectively WF, ZNS, and formalin-ether concentration technique (FECT) for sputum examination of patients with chronic cough; and (4) compared different ZNS procedures. Finally, we assessed excess direct costs associated with the use of different diagnostic techniques.

Principal Findings

Paragonimus eggs were clearly visible in WF and ZNS sputum samples of the index case. They appeared brownish-reddish in ZNS and were detected in 6 of 263 archived ZNS slides corresponding to 5 patients. One hundred sputum samples from 43 patients were examined with three techniques, which revealed that 6 patients had paragonimiasis (13 positive samples). Sensitivity per slide of the FECT, ZNS and the WF technique was 84.6 (p = 0.48), 76.9 (p = 0.25) and 61.5% (p = 0.07), respectively. Percentage of fragmented eggs was below 19% and did not differ between techniques (p = 0.13). Additional operational costs per slide were 0 (ZNS), 0.10 US$ (WF), and 0.79 US$ (FECT). ZNS heated for five minutes contained less eggs than briefly heated slides (29 eggs per slide [eps] vs. 42 eps, p = 0.01). Bloodstained sputum portions contained more eggs than unstained parts (3.3 eps vs. 0.7 eps, p = 0.016).

Conclusions/Significance

Paragonimus eggs can easily be detected in today''s widely used ZNS of sputum slides. The ZNS technique appears superior to the standard WF sputum examination for paragonimiasis and eliminates the risk of tuberculosis transmission. Our findings suggest that ZNS sputum slides should also be examined routinely for Paragonimus eggs. ZNS technique has potential in epidemiological research on paragonimiasis.     

The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies

Background

Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.

Methods

We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.

Results

The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98–1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13–1.48, and recessive model: OR = 1.19, 95% CI = 1.07–1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12–1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04–1.37, and recessive model OR = 1.23, 95% CI = 1.08–1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.

Conclusions

Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.     

Cardiac myosin binding protein C and MAP-kinase activating death domain-containing gene polymorphisms and diastolic heart failure

Objective

Myosin binding protein C (MYBPC3) plays a role in ventricular relaxation. The aim of the study was to investigate the association between cardiac myosin binding protein C (MYBPC3) gene polymorphisms and diastolic heart failure (DHF) in a human case-control study.

Methods

A total of 352 participants of 1752 consecutive patients from the National Taiwan University Hospital and its affiliated hospital were enrolled. 176 patients diagnosed with DHF confirmed by echocardiography were recruited. Controls were matched 1-to-1 by age, sex, hypertension, diabetes, renal function and medication use. We genotyped 12 single nucleotide polymorphisms (SNPs) according to HapMap Han Chinese Beijing databank across a 40 kb genetic region containing the MYBPC3 gene and the neighboring DNA sequences to capture 100% of haplotype variance in all SNPs with minor allele frequencies ≧5%. We also analyzed associations of these tagging SNPs and haplotypes with DHF and linkage disequilibrium (LD) structure of the MYBPC3 gene.

Results

In a single locus analysis, SNP rs2290149 was associated with DHF (allele-specific p = 0.004; permuted p = 0.031). The SNP with a minor allele frequency of 9.4%, had an odds ratio 2.14 (95% CI 1.25–3.66; p = 0.004) for the additive model and 2.06 for the autosomal dominant model (GG+GA : AA, 95% CI 1.17–3.63; p = 0.013), corresponding to a population attributable risk fraction of 12.02%. The haplotypes in a LD block of rs2290149 (C-C-G-C) was also significantly associated with DHF (odds ratio 2.10 (1.53–2.89); permuted p = 0.029).

Conclusions

We identified a SNP (rs2290149) among the tagging SNP set that was significantly associated with early DHF in a Chinese population.     

Genotypic diversity and drug susceptibility patterns among M. tuberculosis complex isolates from South-Western Ghana

Objective

The aim of this study was to use spoligotyping and large sequence polymorphism (LSP) to study the population structure of M. tuberculosis complex (MTBC) isolates.

Methods

MTBC isolates were identified using standard biochemical procedures, IS6110 PCR, and large sequence polymorphisms. Isolates were further typed using spoligotyping, and the phenotypic drug susceptibility patterns were determined by the proportion method.

Result

One hundred and sixty-two isolates were characterised by LSP typing. Of these, 130 (80.25%) were identified as Mycobacterium tuberculosis sensu stricto (MTBss), with the Cameroon sub-lineage being dominant (N = 59/130, 45.38%). Thirty-two (19.75%) isolates were classified as Mycobacterium africanum type 1, and of these 26 (81.25%) were identified as West-Africa I, and 6 (18.75%) as West-Africa II. Spoligotyping sub-lineages identified among the MTBss included Haarlem (N = 15, 11.53%), Ghana (N = 22, 16.92%), Beijing (4, 3.08%), EAI (4, 3.08%), Uganda I (4, 3.08%), LAM (2, 1.54%), X (N = 1, 0.77%) and S (2, 1.54%). Nine isolates had SIT numbers with no identified sub-lineages while 17 had no SIT numbers. MTBss isolates were more likely to be resistant to streptomycin (p<0.008) and to any drug resistance (p<0.03) when compared to M. africanum.

Conclusion

This study demonstrated that overall 36.4% of TB in South-Western Ghana is caused by the Cameroon sub-lineage of MTBC and 20% by M. africanum type 1, including both the West-Africa 1 and West-Africa 2 lineages. The diversity of MTBC in Ghana should be considered when evaluating new TB vaccines.     

Human papillomavirus-16 infection in advanced oral cavity cancer patients is related to an increased risk of distant metastases and poor survival

Background

Human papillomavirus (HPV) is an oncogenic virus causing oropharyngeal cancers and resulting in a favorable outcome after the treatment. The role of HPV in oral cavity squamous cell carcinoma (OSCC) remains ambiguous.

Objective

This study aimed to examine the effect of HPV infection on disease control among patients with OSCC following radical surgery with radiation-based adjuvant therapy.

Patients and Method

We prospectively followed 173 patients with advanced OSCC (96% were stage III/IV) who had undergone radical surgery and adjuvant therapy between 2004 and 2006. They were followed between surgery and death or up to 60 months. Surgical specimens were examined using a PCR-based HPV blot test. The primary endpoints were the risk of relapse and the time to relapse; the secondary endpoints were disease-free survival, disease-specific survival, and overall survival.

Results

The prevalence of HPV-positive OSCC was 22%; HPV-16 (9%) and HPV-18 (7%) were the genotypes most commonly encountered. Solitary HPV-16 infection was a poor predictor of 5-year distant metastases (hazard ratio, 3.4; 95% confidence interval, 1.4–8.0; P = 0.005), disease-free survival (P = 0.037), disease-specific survival (P = 0.006), and overall survival (P = 0.010), whereas HPV-18 infection had no impact on 5-year outcomes. The rate of 5-year distant metastases was significantly higher in the HPV-16 or level IV/V metastasis group compared with both the extracapsular spread or tumor depth ≥11-mm group and patients without risk factors (P<0.001).

Conclusions

HPV infections in advanced OSCC patients are not uncommon and clinically relevant. Compared with HPV-16-negative advanced OSCC patients, those with a single HPV-16 infection are at higher risk of distant metastases and poor survival despite undergoing radiation-based adjuvant therapy and require a more aggressive adjuvant treatment and a more thorough follow-up.     

Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography

Background

In standard reference sources, the incidence of coronary artery disease (CAD) in patients with atrial fibrillation (AF) ranged between 24 and 46.5%. Since then, the incidence of cardiovascular risk factors (CRF) has increased and modern treatment strategies (“pill in the pocket”) are only applicable to patients without structural heart disease. The aim of this study was to investigate the incidence and severity of CAD in patients with AF.

Methods

From January 2005 until December 2009, we included 261 consecutive patients admitted to hospital with paroxysmal, persistent or permanent AF in this prospective study. All patients underwent coronary angiography and the Framingham risk score (FRS) was calculated. Patients with previously diagnosed or previously excluded CAD were excluded.

Results

The overall incidence of CAD in patients presenting with AF was 34%; in patients >70 years, the incidence of CAD was 41%. The incidence of patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) was 21%. Patients with CAD were older (73±8 years vs 68±10 years, p = 0.001), had significantly more frequent hypercholesterolemia (60% vs 30%, p<0.001), were more frequent smokers (26% vs 13%, p = 0.017) and suffered from angina more often (37% vs 2%, p<0.001). There was a significant linear trend among the FRS categories in percentage and the prevalence of CAD and PCI/CABG (p<0.0001).

Conclusions

The overall incidence of CAD in patients presenting with AF was relatively high at 34%; the incidence of PCI/CABG was 21%. Based upon increasing CRF in the western world, we recommend a careful investigation respecting the FRS to either definitely exclude or establish an early diagnosis of CAD – which could contribute to an early and safe therapeutic strategy considering type Ic antiarrhythmics and oral anticoagulation.     

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.