A case‐control study and meta‐analysis reveal the association between COX‐2 G‐765C polymorphism and primary end‐stage hip and knee osteoarthritis

Background

Osteoarthritis (OA) is a popular arthrosis featured as pain, limited joint activity, and deformity. Cyclooxygenase‐2 (COX‐2) has been reported to be up‐regulated in arthritic tissues and is integral to the progression of osteoarthritis (OA). Previous studies showed the COX‐2 promoter G‐765C polymorphism could influence COX‐2 expression. However, the relationship between the variant and OA risk is contrasting.

Methods

We conducted a case‐control study with 196 primary end‐stage hip and knee OA cases and 196 controls in a Chinese Han population. Subsequently, we integrated this case‐control study in a meta‐analysis to acquire greater statistical power. The results from our case‐control study using MassARRAY genotyping technology and binary logistic regression statistical methods.

Results

The variant carriers in the Chinese Han population had a lower primary end‐stage hip and knee OA susceptibility (C vs G: OR = 0.350, 95%CI: 0.154‐0.797, P = .012; GC vs GG: adjusted OR = 0.282, 95%CI: 0.118‐0.676, P = .005). Stratification studies indicated that a higher GC frequency in women decreased not only knee OA susceptibility but also unilateral knee OA risk. The meta‐analysis showed that the variant exhibited a significantly decreased OA risk through comparisons involving allelic, homozygous, heterozygous, and dominant models.

Conclusion

Our findings suggest that the COX‐2 G‐765C polymorphism exerts a protective effect against primary end‐stage knee osteoarthritis in a female Chinese Han population.

     

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk,higher disease severity and elevated inflammation in patients with coronary artery disease

Background

This study aimed to investigate the associations of circulating long, non‐coding (lncRNA) IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 relative expressions with disease risk, severity and inflammatory cytokines levels in coronary artery disease (CAD) patients.

Methods

One hundred and ninety‐one patients suspected of CAD who underwent coronary angiography were consecutively enrolled in this casecontrol study, and divided into CAD patients (N = 102) and controls (N = 89) according to coronary angiographic results. Blood samples of all participants were collected. Plasma lncRNA IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 expressions were detected using quantitative polymerase chain reaction (qPCR). Serum tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17 were assessed using enzyme‐linked immunosorbent assay (ELISA). Gensini Score was used to evaluate the disease severity of CAD patients.

Results

LncRNA IFNG‐AS1 relative expression in CAD patients was upregulated compared with that in controls (P < .001), and the receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of lncRNA‐IFNG‐AS1 for predicting the risk of CAD was 0.755 (95% CI: 0.688‐0.821). lncRNA IFNG‐AS1 relative expression was remarkably associated with Gensini Score (r = .259, P = .009). Additionally, lncRNA IFNG‐AS1 relative expression was positively associated with high‐sensitivity C‐reactive protein (hs‐CRP) (r = .283, P = .004), TNF‐α (r = .269, P = .006), and IL‐6 levels (r = .425, P < .001), while it was negatively correlated with IL‐10 level (r = −.263, P = .008). lncRNA ANRIL or lncRNA ITSN1 was not correlated with CA D risk, Gensini Score, hs‐CRP, ESR, TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, or IL‐17 levels (all P > .05).

Conclusion

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in CAD patients.

     

Opposite impact of Methylene tetrahydrofolate reductase C677T and Methylene tetrahydrofolate reductase A1298C gene polymorphisms on systemic inflammation

Background

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been found to be related with many diseases. Systemic inflammation is now considered as a major predisposition factor for diseases including diabetes mellitus (DM), coronary arterial disease (CAD), stroke, and cancer. This study aimed to investigate whether systemic inflammation is a possible underlying pathogenesis for MTHFR gene polymorphism‐related disease.

Methods

A total of 292 patients were enrolled, and single nucleotide polymorphisms for MTHFR C667T and A1298C were genotyped. Systemic inflammation markers, neutrophil‐to‐lymphocyte ratio (NLR), and platelet‐to‐lymphocyte ratio (PLR) were collected.

Results

In our study population, MTHFR 677 variants had significant higher NLR level than MTHFR 677 wild type (3.77 ± 0.26 vs 3.06 ± 0.18, P = .028). Logistic regression analysis showed that MTHFR 677 variants were significantly associated with increased NLR level. MTHFR 1298 variants showed the opposite effects which tended to have lower level of NLR (3.21 ± 0.16 vs 3.79 ± 0.34, P = .087) and PLR (137.0 ± 4.8 vs 157.7 ± 9.4, P = .052) than MTHFR 1298 wild type. General linear model showed that there was no statistically significant interaction between MTHFR C667T and A1298C gene polymorphism on NLR or PLR.

Conclusions

This study indicates that MTHFR C677T and MTHFR A1298C gene polymorphisms have opposite effect on systemic inflammation, and systemic inflammation may contribute to the pathogenesis for diseases associated with MTHFR C667T gene polymorphism.

     

Evaluation of vitamin D receptor gene polymorphisms (Fok‐I and Bsm‐I) in T1DM Saudi children

Background

Vitamin D deficiency conferred strongest susceptibility to pathogenesis of type 1 diabetes mellitus (T1DM). Altered gene expression and function have strong effect on VDR gene polymorphism.

Objectives

We aimed to check for the association of two single nucleotide polymorphisms (SNPs) in VDR gene (Fok‐I and Bsm‐I) with T1DM in Saudi children.

Subjects and Methods

Cross‐sectional study included 100 T1DM Saudi children, plus 102 unrelated healthy subjects. PCR technique was used for detection of Fok‐I and Bsm‐I SNPs in VDR gene.

Results

Regarding the Fok‐I polymorphisms, T1DM cases showed a significant increased frequency of the heterozygous genotype (Ff) than controls (33% vs 21%, OR = 1.9, 95% CI = 1.006‐3.587, P = .04). In the meantime, they showed significantly lower frequency of the homozygous (ff) genotype (64% vs 79%, OR = 0.51, 95% CI = 0.28‐0.96, P = .03). Cases showed also a significantly lower frequency of the (f) allele than controls (80.5% vs 87.7%, OR = 0.57, 95% CI = 0.33‐0.995, P = .04). On the other hand, cases showed significantly higher frequency of the Bsm‐I homozygous (bb) and heterozygous (Bb) genotypes (25% vs 11.8%, P = .01, OR = 2.5, 95% CI = 1.18‐5.31) & (45% vs 27.5%, P = .0, OR = 2.1, 95 % CI = 1.20‐3.89, respectively). Cases showed also significantly higher frequency of (b) allele compared to control (47.5% vs 25.5%, P = .0, OR = 2.6, 95% CI = 1.74‐4.02). Haplotype analysis showed an increased risk with the fB and fb haplotypes.

Conclusion

This study emphasizes a positive association between SNPs (Fok‐I and Bsm‐I) and T1DM among Saudi children with increased risk with the Fok‐I F and Bsm‐I b alleles.

     

Impact of glucose and lipid markers on the correlation of calculated and enzymatic measured low‐density lipoprotein cholesterol in diabetic patients with coronary artery disease

Background and Aims

Low‐density lipoprotein cholesterol (LDL‐C) is widely estimated by Friedewald equation (FE) and Enzymatic test (ET), which are affected by several factors. The aim of this study was to observe the impact of diabetic lipid and glucose patterns on the correlation between FE LDL‐C (F‐LDL) and ET LDL‐C (E‐LDL) in patients with coronary artery disease (CAD).

Methods and Results

A total of 8155 CAD patients were consecutively enrolled and their lipid profiles were measured. The impacts of triglyceride (TG), glycosylated hemoglobin A1c (HbA1c), and high‐density lipoprotein cholesterol (HDL‐C) on the correlation of F‐LDL and E‐LDL were examined. The difference value (DV) between F‐LDL and E‐LDL was compared using ANOVA test. The CAD patients with DM were elder and had higher body mass index, plasma TG compared with those without DM (P < .05 separately). In the whole population, F‐LDL was lower than E‐LDL but showed a high correlation with E‐LDL (r = .970, P = .000). Moreover, as the TG concentrations increased, the DV increased accordingly but the correlation between F‐LDL and E‐LDL decreased (P < .01). The similar trend was also found in both DM and non‐DM patients comparing with different TG groups. However, in patients with DM, there was no significant difference of DV in different HbA1c groups or HDL‐C concentrations (P > .05).

Conclusion

Although F‐LDL might underestimate the value of LDL‐C, the correlation between F‐LDL and E‐LDL was clinically acceptable (r = .97), suggesting the LDL‐C values measured by two methods were similarly reliable in CAD patients with or without DM.

     

Serum paraoxonase‐1 activity is inversely related to free thyroxine in euthyroid subjects: The PREVEND Cohort Study

Background

Low‐normal thyroid function within the euthyroid range has been suggested to enhance atherosclerosis susceptibility. Paraoxonase‐1 (PON‐1) may protect against atherosclerotic cardiovascular disease development by attenuating oxidative stress. We evaluated relationships of PON‐1 with thyroid stimulating hormone (TSH), free T₄, free T₃, lipids and apolipoprotein (apo)A‐I in euthyroid subjects, and assessed whether such relationships are modified in the context of the metabolic syndrome (MetS).

Materials and methods

Serum PON‐1 activity (arylesterase activity), TSH, free T₄, free T₃, lipids and apoA‐I was measured in 2206 euthyroid subjects (aged 28‐75 years; 1138 men (age 49 ± 13 years) and 1068 women (age 46 ± 12 years), recruited from the general population (PREVEND cohort).

Results

In age‐ and sex‐adjusted analysis, PON‐1 activity (divided into tertiles) was positively related to TSH (β = ?0.045, P = .036) and inversely to free T₄ (β = ?0.042, P = .050) but not to free T₃ (β = ?0.027, P = .20). PON‐1 activity was positively related to total cholesterol, non‐HDL cholesterol and triglycerides, as well as to HDL cholesterol and apoA‐I (P < .01 to <.001). The inverse relationship of PON‐1 activity with free T₄ remained present after adjustment for lipids and other potential confounders (β = ?0.066, P = .002), but the positive relationship with TSH lost significance (β = 0.034, P = .11). The inverse relationship of PON‐1 activity with free T₄ was not different in subjects with vs without MetS (P = .94), nor modified by the presence of its individual components (P ≥ .22 for each).

Conclusions

Serum PON‐1 activity is inversely associated with free T₄ in euthyroid subjects, suggesting that low‐normal thyroid function may affect PON‐1 regulation.     

Rapid on‐site evaluation of routine biochemical parameters to predict right ventricular dysfunction in and the prognosis of patients with acute pulmonary embolism upon admission to the emergency room

Introduction

Patients with acute pulmonary embolism(APE)who present with right ventricular dysfunction (RVD) have a worse prognosis. This study aimed to evaluate the value of routine biochemical parameters in predicting RVD and 30‐day mortality in patients with APE.

Methods

We retrospectively collected the clinical data for 154 enrolled patients, including the neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), D‐dimer, cardiac troponin I (cTnI), and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We analyzed the correlation between RVD and the parameters and conducted a receiver operating characteristic (ROC) curve to confirm the cut‐off values for predicting RVD and 30‐day mortality. Formulas were built with relevant parameters to predict RVD and 30‐day mortality.

Results

Age, NLR, PLR, D‐dimer, the ratio of cTnI (+), and NT‐proBNP (+) were significantly higher in RVD (+) patients. The ratio of cTnI (+) and NT‐proBNP (+) in 30‐day mortality (+) patients was significantly higher than that in 30‐day mortality (−) patients. According to the logistic regression analysis, NLR, cTnI (+), and NT‐proBNP (+) correlated with RVD. The formula for the RVD risk score is 0.072 × NLR+1.460 × NT‐proBNP (+)+2.113 × cTnI (+), and the area under the curve (AUC) = 0.890 (95% CI: 0.839‐0.941, P = .001). The formula for the 30‐day mortality risk score is 0.115 × NLR + 2.046 × NT‐proBNP (+) + 1.946 × cTnI (+) −0.016 × PLR, and the AUC = 0.903 (95% CI: 0.829‐0.976, P = .001).

Conclusions

The rapid on‐site evaluation of routine biochemical parameters, including NLR, cTnI, and NT‐proBNP levels, and the formula developed using these parameters are valuable for predicting RVD and 30‐day mortality in patients with APE.

     

Red blood cell distribution width as a predictor of atrial fibrillation

Background

Current evidence suggests that a higher red blood cell distribution width (RDW) may be associated with increased risk of atrial fibrillation (AF) development. Given that some controversial results have been published, we conducted a systematic review of the current literature along with a comprehensive meta‐analysis to evaluate the association between RDW and AF development.

Methods

We performed a systematic search of the literature using electronic databases (PubMed, Ovid, Embase, and Web of Science) to identify studies reporting on the association between RDW and AF development published until June 2016. We used both fix‐effects and random‐effects models to calculate the overall effect estimate. An I² > 50% indicates at least moderate statistical heterogeneity. A sensitivity analysis and subgroup analysis were performed to find the origin of heterogeneity.

Results

A total of 12 studies involving 2721 participants were included in this meta‐analysis. The standardized mean difference in the RDW levels between patients with and those without AF development was 0.66 units (P < .05; 95% confidence interval 0.44‐0.88). A significant heterogeneity between the individual studies was observed (P < .05; I² = 80.4%). A significant association between the baseline RDW levels and AF occurrence or recurrence following cardiac procedure or surgery was evident (SMD: 0.61; 95% confidence interval 0.33‐0.88; P < .05) with significant heterogeneity across the studies (I² = 80.7%; P < .01).

Conclusions

Our comprehensive meta‐analysis suggests that higher levels of RDW are associated with an increased risk of AF in different populations.

     

High‐density lipoprotein from end‐stage renal disease patients exhibits superior cardioprotection and increase in sphingosine‐1‐phosphate

Background

Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high‐density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine‐1‐phosphate (S1P), HDL‐associated S1P (HDL‐S1P) and HDL‐mediated protection against oxidative stress between CKD and control patients.

Methods

High‐density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL‐S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin‐induced oxidative stress in vitro were measured.

Results

Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro‐inflammatory cytokines (TNF‐alpha and IL‐6). Unexpectedly, HDL‐S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL‐S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively.

Discussion

The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL‐mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL‐S1P.     

Changes in paced signals may predict in‐hospital cardiac arrest

1 Background

An increasing number of patients with chronic illnesses have implanted cardiac rhythm devices such as pacemakers and implantable cardioverter‐defibrillators (ICDs). This study was conducted to identify potentially useful predictors of in‐hospital cardiac arrest (I‐HCA) within paced electrocardiogram (ECG) signals from cardiovascular patients with implanted medical devices.

2 Methods

In this retrospective study of 17 subjects, full‐disclosure ECG traces prior to the time of documented I‐HCA were analyzed to determine R‐R intervals and QRS durations (QRSd).

3 Results

Ventricular paced QRSd prolongation was observed prior to I‐HCA in 10/16 (63%) subjects. QRSd was significantly greater immediately preceding cardiac arrest than during each of the 8 hours prior to cardiac arrest (P < 0.05). Heart rate changes (measured using standard deviation) within 15 minutes of cardiac arrest were significantly greater in subjects with pulseless electrical activity (PEA)/asystolic arrest compared to those with cardiac arrests due to ventricular tachycardia/ventricular fibrillation (VT/VF) (10.13 vs 3.31; P  =  0.024). Significant differences over the 8 hours preceding cardiac arrest in heart rate (74 vs 86 beats/min; P  =  0.002) and QRS duration (172 ms vs 137 ms; P < 0.001) were observed between subjects with initial rhythms of VT/VF and those with initial rhythms of PEA/asystole.

4 Conclusions

Patterns of diagnostic ECG features can be extracted from the telemetry data of patients with implanted medical devices prior to adverse events including I‐HCA. The detection of these significant changes might have an immediate prognostic impact on the timely treatment of some patients at risk of adverse events.     

Clinical effectiveness and cost‐effectiveness of nurse‐led care in Chinese patients with rheumatoid arthritis: A randomized trial comparing with rheumatologist‐led care

Background and aim

The concept of nurse‐led care (NLC) was not familiar in China. This study was designed to evaluate the clinical effectiveness and cost‐effectiveness of NLC versus rheumatologist‐led care (RLC) in Chinese patients with rheumatoid arthritis (RA).

Methods

Patients of either gender (aged ≥18 years) with RA were enrolled at Wenhai Central Hospital, China (January 2015 to December 2015). The participants were then randomized to NLC or RLC. Outcomes of both the groups were compared in terms of effectiveness by measuring the Disease Activity Score 28, visual analogue scores pertaining to pain and fatigue, and duration of morning stiffness. Costs associated with resource use for RA were assessed and compared between both groups.

Results

A total of 214 RA patients in 2 groups (n = 107 in each group) were enrolled and analysed. Improvements in clinical outcomes (disease activity, pain, fatigue, and morning stiffness) over 12 months were significantly greater in the NLC group compared to RLC (P < 0.001). Overall, costs associated with resource use were higher in the RLC group compared to the NLC group (P < 0.05).

Conclusions

Our preliminary finding suggested that RA patients managed by NLC compared to RLC may have better clinical outcomes and more cost‐effective care in China.     

Self‐management programmes for people living with chronic obstructive pulmonary disease: a call for a reconceptualisation

Aims and objectives

To synthesise findings from previously published studies on the effectiveness of self‐management programmes for people with chronic obstructive pulmonary disease.

Background

Self‐management is a widely valued concept to address contemporary issues of chronic health problems. Yet, findings of self‐management programmes for people with chronic obstructive pulmonary disease are indecisive.

Design

Literature review of (1) previously published systematic reviews and (2) an integrative literature review.

Method

Synthesis of findings from previously published systematic reviews (n = 4) of the effectiveness of self‐management programmes for people with chronic obstructive pulmonary disease and an integrated review that was performed on papers published between January 2007–June 2012 (n = 9).

Results

Findings demonstrate that there are few studies on the effectiveness of self‐management programmes on people with chronic obstructive pulmonary disease despite more than a decade of research activities. Outcomes of the studies reveal some increase in health‐related quality of life and reduction in use of healthcare resources. The methodological approaches vary, and the sample size is primarily small. Families are not acknowledged. Features of patient‐centredness exist in self‐management programmes, particularly in the more recent articles.

Conclusions

The effectiveness of self‐management programmes for people with chronic obstructive pulmonary disease remains indecisive.

Relevance to clinical practice

A reconceptualisation of self‐management programmes is called for with attention to a family‐centred, holistic and relational care focusing on living with and minimising the handicapping consequences of the health problems in their entirety.     

Polypoidal choroidal vasculopathy treatment options: A meta‐analysis

Background

Combined treatment with intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) and verteporfin photodynamic therapy (PDT) is widely used for patients with polypoidal choroidal vasculopathy (PCV), although clinical evidence regarding the therapeutic efficacy and safety of such treatment remains lacking.

Design/Methods

We performed a meta‐analysis of previously reported studies comparing combination treatment, PDT monotherapy, and anti‐VEGF monotherapy. Primary outcome measures included changes in best‐corrected visual acuity (BCVA) and central retinal thickness (CRT). The proportion of patients with polyp regression was regarded as the secondary outcome measure.

Results

Twenty studies (three RCTs and 19 retrospective studies) involving 1,178 patients with PCV were selected. Significant differences in the proportion of patients with polyps were observed between the PDT and anti‐VEGF monotherapy groups at 3 and ≥6 months (P < .00001; and P = .0001, respectively). Significantly greater reductions in CRT were observed in the anti‐VEGF than in the PDT group at the 3‐month follow‐up (P = .04). Significantly greater improvements in BCVA were observed in the combined therapy group than in the PDT monotherapy group at 3, 6, 12, and 24 months (P = .03; P = .005; P = .02; and P < .00001, respectively). Combined treatment also resulted in significantly greater improvements in BCVA than monotherapy with anti‐VEGF at 6 and 24 months (P = .001; P < .00001, respectively), and significantly greater polyp regression than that observed following anti‐VEGF treatment at 3 and ≥6 months (P < .00001; P < .0001, respectively).

Conclusions

Combined therapy involving anti‐VEGF agents and PDT may be more effective in improving long‐term outcomes for patients with PCV than monotherapy.     

Adenosine‐sensitive Wolff‐Parkinson‐White: Longer time across the atrioventricular groove

1 Background

Successful ablation sites in Wolff‐Parkinson‐White syndrome (WPW) are characterized by short atrioventricular (AV) intervals. Approximately 15% of patients with WPW have adenosine‐sensitive accessory pathways (APs). We sought to determine if local AV intervals of adenosine‐sensitive APs are different from those of adenosine‐insensitive APs in patients with WPW.

2 Methods

Patients ≤21 years with WPW and adenosine‐sensitive APs who underwent successful ablation over a 9‐year period were included. Patients with WPW and adenosine‐insensitive APs were matched by age and weight in a 1:2 case‐control design. AP location, antegrade and retrograde conduction properties, supraventricular tachycardia (SVT) inducibility, local AV interval, interval from delta wave onset to local ventricular activation (del‐V), and time to loss of preexcitation were reviewed.

3 Results

Fourteen patients with adenosine‐sensitive APs and 28 with adenosine‐insensitive APs were included. Patients with adenosine‐sensitive APs had minimum 1:1 antegrade AP conduction at a longer median paced cycle length (380, interquartile range [IQR] 295 to 585 ms vs 290, IQR 250 to 330 ms, P = 0.046), were less likely to have inducible SVT (35.7% vs 75.0%, P = 0.035), and had a longer median local AV interval (40.5, IQR 30.8 to 58.3 ms vs 32.0, IQR 29.3 to 37.8 ms, P = 0.029) when compared to those with adenosine‐insensitive APs.

4 Conclusion

Patients with WPW and adenosine‐sensitive APs have 1:1 antegrade AP conduction at longer cycle lengths, lower likelihood of SVT induction, and longer local AV intervals when compared to those with adenosine‐insensitive APs. In patients with WPW, it may be important to consider adenosine response when selecting appropriate ablation targets.     

Transient elevation of neutrophil proteinases in induced sputum during COPD exacerbation

Objective. Patients with chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations associated with increased morbidity and mortality. One potential group of enzymes causing tissue destruction in this disease includes neutrophil proteinase elastase (NE), collagenase‐2 (matrix metalloproteinase‐8 (MMP‐8)) and gelatinase B (MMP‐9). We investigated the activity of NE and the levels of MMP‐8 and MMP‐9 in a longitudinal setting at and after COPD exacerbation using a non‐invasive technique, i.e. induced sputum, to ascertain whether these proteinases play a role in COPD exacerbation. Material and methods. The study included healthy non‐smokers (n = 32), healthy smokers (n = 28), patients with stable COPD (n = 15), COPD patients with acute exacerbations (exa) (n = 10) and their recovery (n = 8) after 4 weeks. NE activity by synthetic peptide substrate and spectrophotometry, MMP‐8 levels by immunofluorometry and MMP‐9 levels by ELISA were analysed from induced sputum supernatants. Results. NE activity and the level of MMP‐8 increased highly significantly in patients with COPD exacerbation compared to stable COPD and controls (NE: p = 0.001 and p<0.0001; MMP‐8: p<0.001 and p<0.0001). Paired samples showed a decrease of these proteinases during the recovery period after exacerbation (p = 0.03, p = 0.04). The proteinase levels correlated not only with the percentage and number of neutrophils but also with the lung function parameters (FEV1/FVC and diffusion capacity). Conclusions. COPD exacerbations are associated with neutrophil recruitment into the airways but also transient activation and/or elevation of tissue destruction proteinases, such as NE and MMP‐8, which can be detected from the induced sputum supernatants of these COPD patients.     

Effects of a music‐creation programme on the anxiety,self‐esteem,and quality of life of people with severe mental illness: A quasi‐experimental design

Many studies have shown that music therapy improves patients' symptoms. However, interventions using music creation as their core await further development for patients with severe mental illness (SMI). The current study investigated the effect of a music‐creation programme on the anxiety, self‐esteem, and quality of life of patients with SMI. A quasi‐experimental design using convenience sampling was adopted to recruit patients with SMI from a psychiatric day care centre. Participants were grouped based on their willingness to undergo an intervention (26 patients in the experimental group and 23 patients in the control group). The control groups participated in conventional mental rehabilitation therapy activities. The experimental group participated in a music‐creation session for 90 min every week over a 32‐week period. The outcome indicators before and after the intervention were assessed using the Hamilton Anxiety Rating Scale (HAM‐A), Rosenberg Self‐Esteem Scale (RSES), and World Health Organization Quality of Life‐BREF (WHOQOL‐BREF). Finally, the intervention effect was determined using generalized estimating equations (GEEs). After 32 weeks of intervention activities, the experimental group showed significant improvements in their HAM‐A total scores (P < 0.001) and RSES total scores (P = 0.005). Regarding quality of life, the improvements of the experimental group in terms of the psychological (P = 0.016) and social relationship domains (P = 0.033) were superior to those of the control group. Music‐creation programmes are recommended for inclusion in the routine rehabilitation activities of patients with SMI.     

Reference intervals of carbohydrate antigen 19‐9 in the apparently healthy adult population

Background

To establish reference intervals of carbohydrate antigen 19‐9(CA 19‐9) according to the CLSI CA28‐A3 guideline and to evaluate age‐ and gender‐related variations.

Methods

Serum CA 19‐9 values of 10 149 healthy subjects (from 20 years old to 60 years old) were measured from location health checkups. The relationship between CA 19‐9 and age was analyzed using Spearman's approach. The reference intervals of CA19‐9 were established using Q_2.5 and Q_97.5, and the 90% confidence intervals of upper limits were calculated.

Results

The reference intervals of CA 19‐9 were 1.98‐25.12 U/mL for males (1.97‐25.06 U/mL for 20‐50 years old and 2.31‐26.13 U/mL for 50‐60 years old) and 2.36‐29.29 U/mL for adult (20‐60 years old) females. The upper limit of reference intervals for all individuals was 26.45 U/mL; the level of CA 19‐9 is higher in females than males. Carbohydrate antigen (CA) 19‐9 is significantly associated with aging in adult males(r = .0930, P < .0001), but not in females (P = .4734).

Conclusions

Establishing reference intervals for CA19‐9 and giving age‐related reference intervals of CA19‐9 using a big data of healthy adult, we first discovered that CA19‐9 tends to increase with age in adult males but not in females.

     

Distinct impacts of heart rate and right atrial‐pacing on left atrial mechanical activation and optimal AV delay in CRT

1 Background

Controversy exists regarding how atrial activation mode and heart rate affect optimal atrioventricular (AV) delay in cardiac resynchronization therapy. We studied these questions using high‐reproducibility hemodynamic and echocardiographic measurements.

2 Methods

Twenty patients were hemodynamically optimized using noninvasive beat‐to‐beat blood pressure at rest (62 ± 11 beats/min), during exercise (80 ± 6 beats/min), and at three atrially paced rates: 5, 25, and 45 beats/min above rest, denoted as A_paced,r+5, A_paced,r+25, and A_paced,r+45, respectively. Left atrial myocardial motion and transmitral flow were timed echocardiographically.

3 Results

During atrial sensing, raising heart rate shortened optimal AV delay by 25 ± 6 ms (P < 0.001). During atrial pacing, raising heart rate from A_paced,r+5 to A_paced,r+25 shortened it by 16 ± 6 ms; A_paced,r+45 shortened it 17 ± 6 ms further (P < 0.001). In comparison to atrial‐sensed activation, atrial pacing lengthened optimal AV delay by 76 ± 6 ms (P < 0.0001) at rest, and at ～20 beats/min faster, by 85 ± 7 ms (P < 0.0001), 9 ± 4 ms more (P  =  0.017). Mechanically, atrial pacing delayed left atrial contraction by 63 ± 5 ms at rest and by 73 ± 5 ms (i.e., by 10 ± 5 ms more, P < 0.05) at ～20 beats/min faster. Raising atrial rate by exercise advanced left atrial contraction by 7 ± 2 ms (P  =  0.001). Raising it by atrial pacing did not (P  =  0.2).

4 Conclusions

Hemodynamic optimal AV delay shortens with elevation of heart rate. It lengthens on switching from atrial‐sensed to atrial‐paced at the same rate, and echocardiography shows this sensed‐paced difference in optima results from a sensed‐paced difference in atrial electromechanical delay. The reason for the widening of the sensed‐paced difference in AV optimum may be physiological stimuli (e.g., adrenergic drive) advancing left atrial contraction during exercise but not with fast atrial pacing.