Excess Mortality and Long-Term Disability from Healthcare-Associated Staphylococcus aureus Infections: A Population-Based Matched Cohort Study

Background

Staphylococcus aureus is a leading cause of healthcare-associated infections (HAIs), but the impact of S. aureus HAIs on the long-term survival and functional status of hospitalized patients remain unknown. This study aimed to examine whether S. aureus HAIs increase the risks for long-term mortality and disability.

Methods

We conducted a retrospective population-based matched cohort study of inpatients at 8 medical centers, 43 regional hospitals, and 63 local hospitals which participated in the Taiwan Nosocomial Infection Surveillance (TNIS). We individually matched 3070 patients with S. aureus HAIs to 6140 inpatients without HAIs at a 1∶2 ratio by age, gender, hospital, specialty, underlying diseases, and the length of stay before onset of the S. aureus HAI. Main outcome measures are one-year excess risks for mortality, new-onset chronic ventilator dependence, and new-onset dialysis-dependent end-stage renal disease.

Results

We found that patients with S. aureus HAIs had an excess one-year mortality of 20.2% compared with matched uninfected inpatients (P<0.001). The excess risk for new-onset chronic ventilator dependence and dialysis-dependent end-stage renal disease was 7.3% and 2.6%, respectively (Ps<0.001). S. aureus HAIs were also associated with an excess hospital stay of 12 days and an extra cost of $5978 (Ps<0.001).

Conclusion

S. aureus HAIs have substantial negative effect on the long-term outcome of hospitalized patients in terms of both mortality and disability, which should be taken into consideration in future cost-effectiveness studies of the control and prevention interventions for S. aureus HAIs.     

A Multidisciplinary Intervention to Reduce Infections of ESBL- and AmpC-Producing,Gram-Negative Bacteria at a University Hospital

In response to a considerable increase in the infections caused by ESBL/AmpC-producing Klebsiella pneumonia in 2008, a multidisciplinary intervention, with a main focus on antimicrobial stewardship, was carried out at one university hospital. Four other hospitals were used as controls. Stringent guidelines for antimicrobial treatment and prophylaxis were disseminated throughout the intervention hospital; cephalosporins were restricted for prophylaxis use only, fluoroquinolones for empiric use in septic shock only, and carbapenems were selected for penicillin-allergic patients, infections due to ESBL/AmpC-producing and other resistant bacteria, in addition to their use in severe sepsis/septic shock. Piperacillin-tazobactam ± gentamicin was recommended for empiric treatments of most febrile conditions. The intervention also included education and guidance on infection control, as well as various other surveillances. Two year follow-up data on the incidence rates of patients with selected bacterial infections, outcomes, and antibiotic consumption were assessed, employing before-and-after analysis and segmented regression analysis of interrupted time series, using the other hospitals as controls. The intervention led to a sustained change in antimicrobial consumption, and the incidence of patients infected with ESBL-producing K. pneumoniae decreased significantly (p<0.001). The incidences of other hospital-associated infections also declined (p’s<0.02), but piperacillin-tazobactam-resistant Pseudomonas aeruginosa and Enterococcus faecium infections increased (p’s<0.033). In wards with high antimicrobial consumption, the patient gut carrier rate of ESBL-producing bacteria significantly decreased (p = 0.023). The unadjusted, all-cause 30-day mortality rates of K. pneumoniae and E. coli were unchanged over the four-year period, with similar results in all five hospitals. Although not statistically significant, the 30-day mortality rate of patients with ESBL-producing K. pneumoniae decreased, from 35% in 2008–2009, to 17% in 2010–2011. The two-year follow-up data indicated that this multidisciplinary intervention led to a statistically significant decrease in the incidence of ESBL/AmpC-resistant K. pneumoniae infections, as well as in the incidences of other typical hospital-associated bacterial infections.     

Hydroxyurea affects in vitro porcine oocyte maturation through increased apoptosis and oxidative stress

Hydroxyurea (HU) is an FDA-approved drug used to treat a variety of diseases, especially malignancies, but is harmful to fertility. We used porcine oocytes as an experimental model to study the effect of HU during oocyte maturation. Exposure of cumulus–oocyte complexes (COCs) to 20 µM (P<0.01) and 50 µM (P<0.001) HU reduced oocyte maturation. Exposure to 20 µM HU induced approximately 1.5- and 2-fold increases in Caspase-3 (P<0.001) and P53 (P<0.01) gene expression levels in cumulus cells, respectively, increased Caspase-3 (P<0.01) and P53 (P<0.001) protein expression levels in metaphase II (MII) oocytes and increased the percentage of apoptotic cumulus cells (P<0.001). In addition, HU decreased the mitochondrial membrane potential (Δφm) (P<0.01 and P<0.001) and glutathione (GSH) levels (P<0.01 and P<0.001) of both cumulus cells and MII oocytes, while increasing their reactive oxygen species (ROS) levels (P<0.001). Following parthenogenetic activation of embryos derived from MII oocytes, exposure to 20 µM HU significantly reduced total blastocyst cell numbers (P<0.001) and increased apoptosis of blastocyst cells (P<0.001). Moreover, HU exposure reduced the rate of development of two-celled, four- to eight-celled, blastocyst, and hatching stages after parthenogenetic activation (P<0.05). Our findings indicate that exposure to 20 µM HU caused significant oxidative stress and apoptosis of MII oocytes during maturation, which affected their developmental ability. These results provide valuable information for safety assessments of HU.     

The Effect of Infection Control Nurses on the Occurrence of Pseudomonas aeruginosa Healthcare-Acquired Infection and Multidrug-Resistant Strains in Critically-Ill Children

Background

Healthcare-acquired Pseudomonas aeruginosa (P. aeruginosa) infections in the Pediatric Intensive Care Unit (PICU), which have a high incidence, increase treatment costs and mortality, and seriously threaten the safety of critically ill children. It is essential to seek convenient and effective methods to control and prevent healthcare-acquired infections (HAIs). This research was conducted to study the effect of infection control nurses on the occurrence of P. aeruginosa HAIs and multi-drug resistance (MDR) strains in PICU.

Methods

The clinical data was divided into two groups, with the age ranging from 1 month to 14 years. One group of the critically ill patients(N = 3,722) was admitted to PICU from 2007 to 2010, without the management of infection control nurses. The other group of the critically ill patients (N = 3,943) was admitted to PICU from 2011 to 2013, with the management of infection control nurses. Compare the mortality, morbidity and the incidence of acquired P. aeruginosa infections to evaluate the effect of infection control nurses.

Results

After implementation of the post of infection control nurses, the patient''s overall mortality fell from 4.81% to 3.73%. Among the patients with endotracheal intubation more than 48 hours, the incidence of endotracheal intubation-related pneumonia decreased from 44.6% to 34.32%. The mortality of patients with endotracheal intubation decreased from 16.96% to 10.17%, and the morbidity of HAIs with P. aeruginosa decreased from 1.89% to 1.07%. The mutual different rate (MDR) dropped from 67.95% to 44.23%. There were remarkable differences in these rates between the two groups (p<0.05).

Conclusion

Implementing the post of infection control nurses is associated with effectively reducing the HAI rate, especially the incidence and morbidity of P. aeruginosa HAIs, reducing PICU mortality, improving P. aeruginosa drug resistance.     

The Association of Platelet Count with Clinicopathological Significance and Prognosis in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

ObjectiveElevated platelet count (PC), a measure of systemic inflammatory response, is inconsistently reported to be associated with poor prognosis in patients with renal cell carcinoma (RCC). We conducted a systematic review and meta-analysis to clarify the significance of PC in RCC prognosis.MethodsPubMed, Embase, and Web of Science databases were searched to identify eligible studies to evaluate the associations of PC with patient survival and clinicopathological features of RCC.ResultsWe analyzed 25 studies including 11,458 patients in the meta-analysis and categorized the included articles into three groups based on RCC stage. An elevated PC level was associated with poor overall survival (OS, hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.87-2.67, P<0.001) and cancer-specific survival (CSS, HR 2.59, 95% CI 1.92-3.48, P<0.001) when all stages were examined together; with poor CSS (HR 5.09, 95% CI 2.41-10.73, P<0.001) and recurrence-free survival (HR 6.68, 95% CI 3.35-13.34, P<0.001) for localized RCC; with poor OS (HR 2.00, 95% CI 1.75-2.28, P<0.001) for metastatic RCC; and with poor OS (HR 2.05, 95% CI 1.04-4.03, P = 0.038), CSS (HR 3.38, 95% CI 1.86-6.15, P<0.001), and PFS (HR 2.97, 95% CI 1.47-6.00, P = 0.002) for clear cell RCC. Furthermore, an elevated PC level was significantly associated with TNM stage (OR 3.11, 95% CI 1.59-6.06, P = 0.001), pathological T stage (OR 3.13, 95% CI 2.60-3.77, P<0.001), lymph node metastasis (OR 4.01, 95% CI 2.99-5.37, P<0.001), distant metastasis (OR 3.85, 95% CI 2.46-6.04, P<0.001), Fuhrman grade (OR 3.70, 95% CI 3.00-4.56, P<0.001), tumor size (OR 4.69, 95% CI 2.78-7.91, P<0.001) and Eastern Cooperative Oncology Group score (OR 5.50, 95% CI 3.26-9.28, P<0.001).ConclusionAn elevated PC level implied poor prognosis in patients with RCC and could serve as a readily available biomarker for managing this disease.     

Genetic Variation of the Bloom-Forming Cyanobacterium Microcystis aeruginosa within and among Lakes: Implications for Harmful Algal Blooms

To measure genetic variation within and among populations of the bloom-forming cyanobacterium Microcystis aeruginosa, we surveyed a suite of lakes in the southern peninsula of Michigan that vary in productivity (total phosphorus concentrations of ~10 to 100 μg liter⁻¹). Survival of M. aeruginosa isolates from lakes was relatively low (i.e., mean of 7% and maximum of 30%) and positively related to lake total phosphorus concentration (P = 0.014, r² = 0.407, n = 14). In another study (D. F. Raikow, O. Sarnelle, A. E. Wilson, and S. K. Hamilton, Limnol. Oceanogr. 49:482-487, 2004), survival rates of M. aeruginosa isolates collected from an oligotrophic lake (total phosphorus of ~10 μg liter⁻¹ and dissolved inorganic nitrogen:total phosphorus ratio of 12.75) differed among five different medium types (G test, P of <0.001), with higher survival (P = 0.003) in low-nutrient media (28 to 37% survival) than in high-nutrient media. Even with the relatively low isolate survivorship that could select against detecting the full range of genetic variation, populations of M. aeruginosa were genetically diverse within and among lakes (by analysis of molecular variance, Φ_sc = 0.412 [Φ_sc is an F-statistic derivative which evaluates the correlation of haplotypic diversity within populations relative to the haplotypic diversity among all sampled populations], P = 0.001), with most clones being distantly related to clones collected from lakes directly attached to Lake Michigan (a Laurentian Great Lake) and culture collection strains collected from Canada, Scotland, and South Africa. Ninety-one percent of the 53 genetically unique M. aeruginosa clones contained the microcystin toxin gene (mcyA). Genotypes with the toxin gene were found in all lakes, while four lakes harbored both genotypes possessing and genotypes lacking the toxin gene.     

Differences in Clinical Outcomes According to Weaning Classifications in Medical Intensive Care Units

Background

Although the weaning classification based on the difficulty and duration of the weaning process has been evaluated in the different type of intensive care units (ICUs), little is known about clinical outcomes and validity among the three groups in medical ICU. The objectives of this study were to evaluate the clinical relevance of weaning classification and its association with hospital mortality in a medical ICU with a protocol-based weaning program.

Methods

All consecutive patients admitted to the medical ICU and requiring mechanical ventilation (MV) for more than 24 hours were prospectively registered and screened for weaning readiness by a standardized weaning program between July 2010 and June 2013. Baseline characteristics and outcomes were compared across weaning classifications.

Results

During the study period, a total of 680 patients were weaned according to the standardized weaning protocol. Of these, 457 (67%) were classified as simple weaning, 136 (20%) as difficult weaning, and 87 (13%) as prolonged weaning. Ventilator-free days within 28 days decreased significantly from simple to difficult to prolonged weaning groups (P < 0.001, test for trends). In addition, reintubation within 48 hours after extubation (P < 0.001) and need for tracheostomy during the weaning process (P < 0.001) increased significantly across weaning groups. Finally, ICU (P < 0.001), post-ICU (P = 0.001), and hospital (P < 0.001) mortalities significantly increased across weaning groups. In a multiple logistic regression model, prolonged weaning but not difficult weaning was still independently associated with ICU (adjusted OR 8.265, 95% CI 3.484–19.605, P < 0.001), and post-ICU (adjusted OR 3.180, 95% CI 1.349–7.497, P = 0.005), and hospital (adjusted OR 5.528, 95% CI 2.801–10.910, P < 0.001) mortalities.

Conclusions

Weaning classification based on the difficulty and duration of the weaning process may provide prognostic information for mechanically ventilated patients who undergo the weaning process.     

Persistent Catheter-Related Staphylococcus aureus Bacteremia after Catheter Removal and Initiation of Antimicrobial Therapy

Objectives

Catheter-related Staphylococcus aureus bacteremia (CRSAB) occasionally persists despite catheter removal and initiation of appropriate antimicrobial therapy. The aim of this study was to determine the incidence, risk factors, and outcomes of persistent CRSAB after catheter removal and initiation of antimicrobial therapy.

Methods

Consecutive patients with CRSAB were prospectively included from over a 41-month period. We compared the clinical features, 40 bacterial virulence genes, and outcomes between patients with persistent CRSAB (i.e., bacteremia for >3 days after catheter removal and initiation of appropriate antimicrobial therapy) and non-persistent CRSAB.

Results

Among the 220 episodes of CRSAB, the catheter was kept in place in 17 (6%) and removed in 203 (94%) cases. In 43 (21%) of the 203 episodes, bacteremia persisted for >3 days after catheter removal and initiation of antimicrobial therapy. Methicillin resistance (Odds ratio [OR], 9.01; 95% confidence interval [CI], 3.05–26.61; P<0.001), non-catheter prosthetic devices (OR, 5.37; 95% CI, 1.62–17.80; P = 0.006), and renal failure (OR, 3.23; 95% CI, 1.48–7.08; P = 0.003) were independently associated with persistent CRSAB. Patients with persistent CRSAB were more like to experience complication than were those with non-persistent CRSAB (72% vs. 15%; P<0.001). Among all episodes due to methicillin-resistant S. aureus, persistent CRSAB isolates were associated with accessory gene regulator (agr) group II (P = .04), but presence of other bacterial virulence genes, distribution of vancomycin minimum inhibitory concentration distribution, and frequency of vancomycin heteroresistance did not differ between the groups.

Conclusions

In patients with CRSAB, bacteremia persisted in 21% of cases despite catheter removal and initiation of antimicrobial therapy. Methicillin resistance, renal failure, and non-catheter prosthetic devices were independent risk factors for persistent CRSAB, which was associated with a higher rate of complications.     

Personality,Perceived Environment,and Behavior Systems Related to Future Smoking Intentions among Youths: An Application of Problem-Behavior Theory in Shanghai,China

Background

Smoking among youths is a worldwide problem, particularly in China. Many endogenous and environmental factors influence smokers’ intentions to smoke; therefore, a comprehensive model is needed to understand the significance and relationship of predictors. This study aimed to develop a prediction model based on problem-behavior theory (PBT) to interpret intentions to smoke among Chinese youths.

Methods

We conducted a cross-sectional study of 26,675 adolescents from junior, senior, and vocational high schools in Shanghai, China. Data on smoking status, smoking knowledge, attitude toward smoking, parents’ and peers’ smoking, and media exposure to smoking were collected from students. A structural equation model was used to assess the developed prediction model.

Results

The experimental smoking rate and current smoking rate among the students were 11.0% and 3%, respectively. Our constructed model showed an acceptable fit to the data (comparative fit index = 0.987, root-mean-square error of approximation = 0.034). Intention to smoke was predicted by perceived environment (β = 0.455, P < 0.001) system consisting of peer smoking (β = 0.599, P < 0.001), parent smoking (β = 0.152, P < 0.001), and media exposure to smoking (β = 0.226, P < 0.001), and behavior system (β = 0.487, P < 0.001) consisting of tobacco experimentation (β = 0.663, P < 0.001) and current smoking (β = 0.755, P < 0.001). Smoking intention was irrelevant for personality system in students (β = -0.113, P>0.05) which consisted of acceptance of tobacco use (β = 0.668, P < 0.001) and academic performance (β = 0.171, P < 0.001).

Conclusion

The PBT-based model we developed provides a good understanding of the predictors of intentions to smoke and it suggests future interventions among youths should focus on components in perceived environment and behavior systems, and take into account the moderating effects of personality system.     

Plasma MicroRNAs as Potential Noninvasive Biomarkers for In-Stent Restenosis

Objective

To investigate whether microRNAs (miRs) can serve as novel biomarkers for in-stent restenosis (ISR).

Methods

This retrospective, observational single-centre study was conducted at the cardiovascular department of a tertiary hospital centre in the north of China. Follow-up coronary angiography at 6 to 12 months was performed in 181 consecutive patients implanted with drug-eluting stents. Fifty-two healthy volunteers served as the control group. The plasma miRs levels were analyzed by quantitative real-time PCR. Receiver-operating characteristic curve (ROC) analysis was performed to investigate the characters of these miRs as potential biomarkers of ISR.

Results

MiR-21 levels in ISR patients were significantly higher than those in non-ISR patients and healthy controls (P<0.05), while miR-100 (P<0.05), miR-143 (P<0.001) and miR-145 (P<0.0001) levels were significantly decreased in ISR patients. Further analysis showed that miR-21 levels were remarkably increased (P = 0.045), while miR-100 (P = 0.041), miR-143 (P = 0.029) and miR-145 (P<0.01) levels were dramatically decreased in patients with diffuse ISR compared to those with focal ISR. ROC analysis demonstrated that the area under curve of miR-145, miR-143, miR-100 and miR-21 were 0.880 (95% confidence interval; CI = 0.791–0.987, P<0.001), 0.818 (95% confidence interval; CI = 0.755–0.963, P<0.001), 0.608 (95% confidence interval; CI = 0.372–0.757, P<0.05) and 0.568 (95% confidence interval; CI = 0.372–0.757, P<0.05), with specificity of 83.1%, 80.1%, 68.9% and 68.6%, and sensitivity of 88.7%, 82.1%, 60.2% and 50.1%, respectively.

Conclusions

Circulating miR-143 and miR-145 levels are associated with the occurrence of ISR and can serve as novel noninvasive biomarkers for ISR.     

Effect of Age on Survival Outcome in Operated and Non-Operated Patients with Colon Cancer: A Population-Based Study

Objective

To know the effect of age on survival outcome in operated and non-operated patients with colon cancer.

Methods

From the Surveillance, Epidemiology, and End Results database, we identified 123,356 patients with colon cancer who were diagnosed between 1996 and 2005, grouped them as older or younger than 40 years and analyzed their 5-year cancer-specific survival (CSS) data, along with some risk factors, using Kaplan–Meier methods and multivariable Cox regression models.

Results

The younger group had significantly higher pathological grades (P<0.001), more mucinous and signet-ring histology (P<0.001), advanced AJCC stage (P<0.001), and were more likely to undergo surgery (P<0.001). For surgically treated patients, age did not significantly affect 5-year CSS (younger: 66.7%; older: 67.3%; P = 0.86). Further analysis showed that age was an independent prognostic factor in stage I–IV disease (stage I: P = 0.001; P<0.001 for stages II–IV, in both uni- and multivariate analyses), but not for patients with unknown disease stage (P = 0.52). For non-surgically treated patients, age significantly affected 5-year CSS (younger: 16.2%; older: 12.9%; P<0.001) in univariate analysis; and was an independent prognostic factor (P<0.001) in multivariate analysis.

Conclusion

The CSS rate for younger CC patients was at least as high as for older patients, although they presented with higher proportions of unfavorable factors and more advanced disease.     

MicroRNA-762 Is Upregulated in Human Corneal Epithelial Cells in Response to Tear Fluid and Pseudomonas aeruginosa Antigens and Negatively Regulates the Expression of Host Defense Genes Encoding RNase7 and ST2

Mucosal surfaces regulate defenses against infection and excessive inflammation. We previously showed that human tears upregulated epithelial expression of genes encoding RNase7 and ST2, which inhibited Pseudomonas aeruginosa invasion of human corneal epithelial cells. Here, microRNA microarrays were used to show that a combination of tear fluid exposure (16 h) then P. aeruginosa antigens (3 h) upregulated miR-762 and miR-1207, and down-regulated miR-92 and let-7b (all > 2-fold) in human corneal epithelial cells compared to P. aeruginosa antigens alone. RT-PCR confirmed miR-762 upregulation ∼ 3-fold in tear-antigen exposed cells. Without tears or antigens, an antagomir reduced miR-762 expression relative to scrambled controls by ∼50%, increased expression of genes encoding RNase7 (∼80 %), ST2 (∼58%) and Rab5a (∼75%), without affecting P. aeruginosa internalization. However, P. aeruginosa invasion was increased > 3-fold by a miR-762 mimic which reduced RNase7 and ST2 gene expression. Tear fluid alone also induced miR-762 expression ∼ 4-fold, which was reduced by the miR-762 antagomir. Combination of tear fluid and miR-762 antagomir increased RNase7 and ST2 gene expression. These data show that mucosal fluids, such as tears, can modulate epithelial microRNA expression to regulate innate defense genes, and that miR-762 negatively regulates RNase7, ST2 and Rab5a genes. Since RNase7 and ST2 inhibit P. aeruginosa internalization, and are upregulated by tear fluid, other tear-induced mechanisms must counteract inhibitory effects of miR-762 to regulate resistance to bacteria. These data also suggest a complex relationship between tear induction of miR-762, its modulation of innate defense genes, and P. aeruginosa internalization.     

Mitochondrial Regulation of NADPH Oxidase in Hindlimb Unweighting Rat Cerebral Arteries

Exposure to microgravity results in post-flight cardiovascular deconditioning and orthostatic intolerance in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been indicated in this process. To elucidate the mechanism for this condition, we investigated whether mitochondria regulated NADPH oxidase in hindlimb unweighting (HU) rat cerebral and mesenteric arteries. Four-week HU was used to simulate microgravity in rats. Vascular superoxide generation, protein and mRNA levels of Nox2/Nox4, and the activity of NADPH oxidase were examined in the present study. Compared with control rats, the levels of superoxide increased in cerebral (P<0.001) but not in mesenteric vascular smooth muscle cells. The protein and mRNA levels of Nox2 and Nox4 were upregulated significantly (P<0.001 and P<0.001 for Nox2, respectively; P<0.001 and P<0.001 for Nox4, respectively) in HU rat cerebral arteries but not in mesenteric arteries. NADPH oxidases were activated significantly by HU (P<0.001) in cerebral arteries but not in mesenteric arteries. Chronic treatment with mitochondria-targeted antioxidant mitoTEMPO attenuated superoxide levels (P<0.001), decreased the protein and mRNA expression levels of Nox2/Nox4 (P<0.01 and P<0.05 for Nox2, respectively; P<0.001 and P<0.001 for Nox4, respectively) and the activity of NADPH oxidase (P<0.001) in HU rat cerebral arteries, but exerted no effects on HU rat mesenteric arteries. Therefore, mitochondria regulated the expression and activity of NADPH oxidases during simulated microgravity. Both mitochondria and NADPH oxidase participated in vascular redox status regulation.     

The Association of Brachial-Ankle Pulse Wave Velocity with Coronary Artery Disease Evaluated by Coronary Computed Tomography Angiography

The aim of this study was to investigate whether brachial-ankle pulse wave velocity (baPWV) is associated with the severity of coronary artery disease (CAD) assessed by coronary computed tomography angiography (CCTA), and to evaluate baPWV as a predictor of obstructive CAD on CCTA. A total of 470 patients who underwent both baPWV and CCTA were included. We evaluated stenosis degree and plaque characteristics on CCTA. To estimate the severity of CAD, we calculated the number of segment with plaque (segment involvement score; SIS), stenosis degree-weighted plaque score (segment stenosis score; SSS), and coronary artery calcium score (CACS). The mean baPWV was 1,485 ± 315 cm/s (range, 935-3,175 cm/s). Non-obstructive (stenosis < 50%) and obstructive (stenosis ≥ 50%) CAD was found in 129 patients (27.4%) and 144 (30.6%), respectively. baPWV in patients with obstructive CAD was higher than that of patients with non-obstructive (1,680 ± 396 cm/s versus 1,477 ± 244 cm/s, P < 0.001) or no CAD (1,680 ± 396 cm/s versus ± 196 1,389 cm/s, P < 0.001). baPWV showed significant correlation with SSS (r = 0.429, P < 0.001), SIS (r = 0.395, P < 0.001), CACS (r 0.346, P < 0.001), and the number of segment with non-calcified plaque (r 0.092, P = 0.047), mixed plaque (r = 0.267, P < 0.001), and calcified plaque (r = 0.348, P < 0.001), respectively. The optimal baPWV cut-off value for the detection of obstructive CAD was 1,547 cm/s. baPWV ≥ 1,547 cm/s was independent predictor for the obstructive CAD. In conclusion, baPWV is well correlated with the severity of CAD evaluated by CCTA. baPWV has the potential to predict severity of coronary artery atherosclerosis.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

Khat Chewing Habits in the Population of the Jazan Region,Saudi Arabia: Prevalence and Associated Factors

The use of khat (Catha edulis) is a major public health and social problem that is believed to be growing globally. The khat chewing habit is prevalent in all areas of the Jazan region, Kingdom of Saudi Arabia (KSA). However, few studies have been conducted at the community level to investigate the khat chewing habits in this area. This study was conducted with the aim of assessing the prevalence and predictors of khat chewing among the Jazan community population. A cross-sectional study was conducted with a sample (n = 4,500) of the Jizani population who attended primary heath care centers in Jazan region. The participants were selected using a two-stage cluster random sampling. A structured questionnaire was used for data collection. The overall lifetime prevalence of khat chewing was 33.2% (95% CI 31.8–34.7) and was significantly higher for males 42.2% (95% CI 40.4–43.9) than for females 11.3% (95% CI 9.6–13.1) (P < 0.001). Current khat chewers accounted for 28.7% (95% CI 27.4–30.1) of the population sampled; 36.9% (95% CI 35.2–38.6) of whom were males, which is a significantly higher percentage than the 8.7% (95% CI 7.3–10.4) of current khat chewers who were females (P < 0.001). The multivariate logistic regression analysis suggests that the most important independent predictors of khat chewing were having a friend who chewed khat (OR = 20.1, P < 0.001), participant''s smoking status (OR) = 3.9, P < 0.001), friend''s smoking status (OR = 2.2, P < 0.001), gender (OR = 2.2, P < 0.001) and educational level (OR = 1.5, P < 0.05). A large proportion of the Jizani populations chew khat. Government and non-governmental organizations NGOs should design and strengthen community prevention programs to curb the high prevalence of khat use.     

Role of Calf-Adapted Escherichia coli in Maintenance of Antimicrobial Drug Resistance in Dairy Calves

The prevalence of antimicrobial drug-resistant bacteria is typically highest in younger animals, and prevalence is not necessarily related to recent use of antimicrobial drugs. In dairy cattle, we hypothesize that antimicrobial drug-resistant, neonate-adapted bacteria are responsible for the observed high frequencies of resistant Escherichia coli in calves. To explore this issue, we examined the age distribution of antimicrobial drug-resistant E. coli from Holstein cattle at a local dairy and conducted an experiment to determine if low doses of oxytetracycline affected the prevalence of antimicrobial drug-resistant E. coli. Isolates resistant to tetracycline (>4 μg/ml) were more prevalent in <3-month-old calves (79%) compared with lactating cows (14%). In an experimental trial where calves received diets supplemented with or without oxytetracycline, the prevalence of tetracycline-resistant E. coli was slightly higher for the latter group (P = 0.039), indicating that drug use was not required to maintain a high prevalence of resistant E. coli. The most common resistance pattern among calf E. coli isolates included resistance to streptomycin (>12 μg/ml), sulfadiazine (>512 μg/ml), and tetracycline (>4 μg/ml) (SSuT), and this resistance pattern was most prevalent during the period when calves were on milk diets. To determine if prevalence was a function of differential fitness, we orally inoculated animals with nalidixic acid-resistant strains of SSuT E. coli and susceptible E. coli. Shedding of SSuT E. coli was significantly greater than that of susceptible strains in neonatal calves (P < 0.001), whereas there was no difference in older animals (P = 0.5). These data support the hypothesis that active selection for traits linked to the SSuT phenotype are responsible for maintaining drug-resistant E. coli in this population of dairy calves.     

Effects of Dietary Crude Protein Levels and Cysteamine Supplementation on Protein Synthetic and Degradative Signaling in Skeletal Muscle of Finishing Pigs

Dietary protein levels and cysteamine (CS) supplementation can affect growth performance and protein metabolism of pigs. However, the influence of dietary protein intake on the growth response of CS-treated pigs is unclear, and the mechanisms involved in protein metabolism remain unknown. Hence, we investigated the interactions between dietary protein levels and CS supplementation and the effects of dietary crude protein levels and CS supplementation on protein synthetic and degradative signaling in skeletal muscle of finishing pigs. One hundred twenty barrows (65.84 ± 0.61 kg) were allocated to a 2 × 2 factorial arrangement with five replicates of six pigs each. The primary variations were dietary crude protein (CP) levels (14% or 10%) and CS supplemental levels (0 or 700 mg/kg). The low-protein (LP) diets (10% CP) were supplemented with enough essential amino acids (EAA) to meet the NRC AA requirements of pigs and maintain the balanced supply of eight EAA including lysine, methionine, threonine, tryptophan, valine, phenylalanine, isoleucine, and leucine. After 41 days, 10 pigs per treatment were slaughtered. We found that LP diets supplemented with EAA resulted in decreased concentrations of plasma somatostatin (SS) (P<0.01) and plasma urea nitrogen (PUN) (P<0.001), while dietary protein levels did not affect other traits. However, CS supplementation increased the average daily gain (P<0.001) and lean percentage (P<0.05), and decreased the feed conversion ratio (P<0.05) and back fat (P<0.05). CS supplementation also increased the concentrations of plasma insulin-like growth factor 1 (IGF-1) (P<0.001), and reduced the concentrations of leptin, SS, and PUN (P<0.001). Increased mRNA abundance of Akt1 and IGF-1 signaling (P<0.001) and decreased mRNA abundance of Forkhead Box O (FOXO) 4 (P<0.01) and muscle atrophy F-box (P<0.001) were observed in pigs receiving CS. Additionally, CS supplementation increased the protein levels for the phosphorylated mammalian target of rapamycin (mTOR), eIF-4E binding protein 1, and ribosomal protein S6 kinase 1 (P<0.001). There were no interactions between dietary protein levels and CS supplementation for all traits. In conclusion, dietary protein levels and CS supplementation influenced growth and protein metabolism through independent mechanisms in pigs. In addition, LP diets supplemented with EAA did not affect growth performance and other traits except the concentrations of SS and PUN probably through maintenance of protein synthesis and degradation signaling. Moreover, CS supplementation improved growth performance by increasing plasma IGF-1 concentrations possibly through alterations of mTOR and Akt/FOXO signaling pathways in skeletal muscle of finishing pigs.     

The Primary Resistance of Helicobacter pylori in Taiwan after the National Policy to Restrict Antibiotic Consumption and Its Relation to Virulence Factors—A Nationwide Study

Objective

The Taiwan Government issued a policy to restrict antimicrobial usage since 2001. We aimed to assess the changes in the antibiotic consumption and the primary resistance of H. pylori after this policy and the impact of virulence factors on resistance.

Methods

The defined daily dose (DDD) of antibiotics was analyzed using the Taiwan National Health Insurance (NHI) research database. H. pylori strains isolated from treatment naïve (N=1395) and failure from prior eradication therapies (N=360) from 9 hospitals between 2000 and 2012 were used for analysis. The minimum inhibitory concentration was determined by agar dilution test. Genotyping for CagA and VacA was determined by PCR method.

Results

The DDD per 1000 persons per day of macrolides reduced from 1.12 in 1997 to 0.19 in 2008, whereas that of fluoroquinolones increased from 0.12 in 1997 to 0.35 in 2008. The primary resistance of amoxicillin, clarithromycin, metronidazole, and tetracycline remained as low as 2.2%, 7.9%, 23.7%, and 1.9% respectively. However, the primary levofloxacin resistance rose from 4.9% in 2000–2007 to 8.3% in 2008–2010 and 13.4% in 2011–2012 (p=0.001). The primary resistance of metronidazole was higher in females than males (33.1% vs. 18.8%, p<0.001), which was probably attributed to the higher consumption of nitroimidazole. Neither CagA nor VacA was associated with antibiotic resistance.

Conclusions

The low primary clarithromycin and metronidazole resistance of H. pylori in Taiwan might be attributed to the reduced consumption of macrolides and nitroimidazole after the national policy to restrict antimicrobial usage. Yet, further strategies are needed to restrict the consumption of fluoroquinolones in the face of rising levofloxacin resistance.     

Prevalence and Associations of Incomplete Posterior Vitreous Detachment in Adult Chinese: The Beijing Eye Study

Purpose

To determine prevalence and associations of incomplete posterior vitreous detachment (PVD).

Methods

The population-based cross-sectional Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT). Incomplete PVD was differentiated into type 1 (shallow PVD with circular perifoveal vitreous attachment), type 2 (PVD reaching fovea but not foveola), type 3 (shallow PVD with pinpoint vitreous attachment at the foveola), and type 4 (PVD completely detached from the macula, attached to the optic disc).

Results

An incomplete PVD was detected in 3948 eyes (prevalence: 60.5±0.6%; 95% Confidence Interval (CI): 59.3%,61.7%) of 2198 subjects (67.1±0.8%;95%CI: 65.6%,68.7%). Type 1 PVD was seen in 3090 (78.3%) eyes, type 2 PVD in 504 (12.8%) eyes, type 3 PVD in 70 (1.8%) eyes, and type 4 PVD in 284 (7.2%) eyes. Prevalence of incomplete PVD was associated with younger age (P<0.001;OR:0.91), male gender (P<0.001;OR:0.64), rural region of habitation (P<0.001;OR:0.49), larger corneal diameter (P = 0.04;OR:0.91), better best corrected visual acuity (P = 0.02;OR:0.41), and hyperopic refractive error (P<0.001;OR:1.15). The type of incomplete PVD was associated with higher age (P<0.001), urban region of habitation (P<0.001), myopic refractive error (P = 0.001), thinner cornea (P = 0.005), and better best corrected visual acuity (P = 0.056).

Conclusions

In adult Chinese in Greater Beijing, prevalence of an incomplete PVD (detected in 67.1% subjects) was associated with younger age, male gender, rural region of habitation, larger corneal diameter, better best corrected visual acuity and hyperopic refractive error.