Is Treatment with Trimetazidine Beneficial in Patients with Chronic Heart Failure?

Background

Whether additional benefit can be achieved with the use of trimetazidine (TMZ) in patients with chronic heart failure (CHF) remains controversial. We therefore performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of TMZ treatment in CHF patients.

Methods

We searched PubMed, EMBASE, and Cochrane databases through October 2013 and included 19 RCTs involving 994 CHF patients who underwent TMZ or placebo treatment. Risk ratio (RR) and weighted mean differences (WMD) were calculated using fixed or random effects models.

Results

TMZ therapy was associated with considerable improvement in left ventricular ejection fraction (WMD: 7.29%, 95% CI: 6.49 to 8.09, p<0.01) and New York Heart Association classification (WMD: −0.55, 95% CI: −0.81 to −0.28, p<0.01). Moreover, treatment with TMZ also resulted in significant decrease in left ventricular end-systolic volume (WMD: −17.09 ml, 95% CI: −20.15 to −14.04, p<0.01), left ventricular end-diastolic volume (WMD: −11.24 ml, 95% CI: −14.06 to −8.42, p<0.01), hospitalization for cardiac causes (RR: 0.43, 95% CI: 0.21 to 0.91, p = 0.03), B-type natriuretic peptide (BNP; WMD: −157.08 pg/ml, 95% CI: −176.55 to −137.62, p<0.01) and C-reactive protein (CRP; WMD: −1.86 mg/l, 95% CI: −2.81 to −0.90, p<0.01). However, there were no significant differences in exercise duration and all-cause mortality between patients treated with TMZ and placebo.

Conclusions

TMZ treatment in CHF patients may improve clinical symptoms and cardiac function, reduce hospitalization for cardiac causes, and decrease serum levels of BNP and CRP.     

Impact of Untreated Obstructive Sleep Apnea on Left and Right Ventricular Myocardial Function and Effects of CPAP Therapy

Background

Obstructive sleep apnea (OSA) has deteriorating effect on LV function, whereas its impact on RV function is controversial. We aimed to determine the effect of OSA and continuous positive airway pressure (CPAP) treatment on left and right ventricular (LV, RV) function using transthoracic echocardiography (TTE) and 2 dimensional speckle tracking (2D ST) analysis of RV deformation capability.

Methods and Results

82 patients with OSA and need for CPAP therapy were prospectively enrolled and underwent TTE at study inclusion and after 6 months of follow up (FU). Multivariate regression analysis revealed an independent association between baseline apical right ventricular longitudinal strain (RV-Sl), BMI and the severity of OSA (apical RV-Sl: P = 0.0002, BMI: P = 0.02). After CPAP therapy, LV functional parameters (LVEF: P<0.0001, LV performance index: P = 0.03, stroke volume: P = 0.042), and apical RV-Sl (P = 0.001) improved significantly. The effect of CPAP therapy was related to severity of OSA (LVEF: AHI 5–14, 66.4±8.8%, 68.5±10.6% [P = ns]; AHI 15–30∶59.8±7.7%, 68.6±9.3% [P = 0.002]; AHI>30∶54.1±12.4%, 68.2±13.6%[P<0.0001]; apical RV-Sl: AHI 5–14: −17.3±8.7%, −16.0±10.8% [P = ns], AHI 15–30: −9.8±6.0%, −15.4±10.9% [P = 0.028], AHI>30: −6.3±5.7%, −17.9±11.2% [P<0.0001]).

Conclusions

OSA seems to have deteriorating effect on LV and RV function. We found a beneficial effect of CPAP on LV and RV functional parameters predominately in patients with severe OSA. 2D speckle tracking might be of value to determine early changes in global and regional right ventricular function.     

The Differences in Homocysteine Level between Obstructive Sleep Apnea Patients and Controls: A Meta-Analysis

Background

Studies have reported inconsistent findings regarding the relationship between obstructive sleep apnea (OSA) and homocysteine (HCY) level. This study aimed to assess the difference in plasma HCY level between OSA patients and controls by conducting a meta-analysis of published studies.

Methods

Database of PubMed, SCI, and China National Knowledge Internet (CNKI) were comprehensively searched. Eligible studies regarding plasma HCY level in OSA patients were identified by two independent reviewers. RevMan (version 5.2) and STATA (version 12.0) were employed for data synthesis.

Results

A total of 10 studies involving 432 subjects were included. Meta-analysis showed that plasma HCY levels in OSA group were 3.11 µmol/l higher than that in control group (95% confidence interval: 2.08 to 4.15, P<0.01). Subgroup analysis revealed a more significant differences between OSA patients and controls when average body mass index ≥30 (the total weighted mean difference (WMD) was 3.64), average age<50 (the total WMD was 3.96) and average apnea hypopnea index ≥35 (the total WMD was 4.54).

Conclusions

In this meta-analysis, plasma HCY levels were found to be higher in OSA patients compared to control subjects.     

Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

Background

Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC.

Methods

A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors.

Results

Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043).

Conclusions

Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC.     

Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

Purpose

Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer.

Methods

Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS.

Results

Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively.

Conclusions

This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer.     

Genetic Analysis of the Relationship between Bone Mineral Density and Low-Density Lipoprotein Receptor-Related Protein 5 Gene Polymorphisms

Background

A number of studies have examined the association between the polymorphisms of the low-density lipoprotein receptor-related protein 5 gene (LRP5), but previous results have been inconclusive. Thus we performed a meta-analysis of studies on the association between the LRP5 polymorphisms and bone mineral density (BMD) to assess their pooled effects.

Methods

Published literature from PubMed, EMBASE and ISI web of science were searched for eligible publications. Weighted mean difference (WMD) and 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

A total of 19 studies with 25773 subjects were considered in this meta-analysis. Of them, 17 examined the association between the A1330V polymorphism and BMD, 8 were focused on the V667M polymorphism, and 2 analyzed the Q89R polymorphism. Individuals with the A1330V AA genotype showed significantly higher BMD than those with the AV/VV genotypes [at lumbar spine (LS): WMD = 0.02g/cm², 95% CI = 0.01-0.03, P < 10^-4; at femur neck (FN): WMD = 0.01g/cm², 95% CI = 0.00-0.02, P = 0.01] or VV genotype (at LS: WMD = 0.02g/cm², 95% CI = 0.01-0.04, P = 0.01). Significant associations were also detected in the analysis for V667M (VV vs. VM/MM: WMD at LS = 0.02g/cm², 95% CI = 0.02-0.03, P < 10^-5; WMD at FN = 0.01g/cm², 95% CI = 0.01-0.02, P = 0.0002). As for Q89R, subjects with the QQ genotype tended to have higher BMD than those with the QR/RR genotypes at FN (WMD = 0.03g/cm², 95% CI = 0.01-0.05, P = 0.005).

Conclusion

This meta-analysis demonstrated that the LRP5 polymorphisms may be modestly associated with BMD of LS and FN.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30–98] vs 170 [69–204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13–74] vs 277 [235–288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58–4.69] vs 614 [5.61–7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12–7.58] vs 7.24 [6.22–9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.     

Trans-Lamina Cribrosa Pressure Difference and Open-Angle Glaucoma. The Central India Eye and Medical Study

Purpose

To assess associations of the trans-lamina cribrosa pressure difference (TLCPD) with glaucomatous optic neuropathy.

Methods

The population-based Central India Eye and Medical Study included 4711 subjects. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44 Body Mass Index[kg/m2]+0.16 Diastolic Blood Pressure[mmHg]−0.18×Age[Years] −1.91. TLCPD was IOP–CSFP.

Results

Mean TLCPD was 3.64±4.25 mm Hg in the non-glaucomatous population and 9.65±8.17 mmHg in the glaucomatous group. In multivariate analysis, TLCPD was associated with older age (P<0.001; standardized coefficient beta:0.53; regression coefficient B:0.18; 95% confidence interval (CI):0.17, 0.18), lower body mass index (P<0.001; beta: −0.28; B: −0.36; 95%CI: −0.38, −0.31), lower diastolic blood pressure (P<0.001; beta: −0.31; B: −0.12; 95%CI: −0.13, −0.11), higher pulse (P<0.001; beta:0.05; B:0.02; 95%CI:0.01,0.2), lower body height (P = 0.02; beta: −0.02; B: −0.01; 95%CI: −0.02,0.00), higher educational level (P<0.001; beta:0.04; B:0.15; 95%CI:0.09,0.22), higher cholesterol blood concentrations (P<0.001; beta:0.04; B:0.01; 95%CI:0.01,0.01), longer axial length (P = 0.006; beta:0.03; B:0.14; 95%CI:0.04,0.24), thicker central cornea (P<0.001; beta:0.15; B:0.02; 95%CI:0.02,0.02), higher corneal refractive power (P<0.001; beta:0.07; B:0.18; 95%CI:0.13,0.23) and presence of glaucomatous optic neuropathy (P<0.001; beta:0.11; B:3.43; 95%CI:2.96,3.99). Differences between glaucomatous subjects and non-glaucomatous subjects in CSFP were more pronounced for open-angle glaucoma (OAG) than for angle-closure glaucoma (ACG) (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for ACG than for OAG (8.5 mmHg versus 3.0 mmHg). Presence of OAG was significantly associated with TLCPD (P<0.001; OR:1.24; 95%CI:1.19,1.29) but not with IOP (P = 0.08; OR:0.96; 95%CI:0.91,1.00). Prevalence of ACG was significantly associated with IOP (P = 0.04; OR:1.19; 95%CI:1.01,1.40) but not with TLCPD (P = 0.92).

Conclusions

In OAG, but not in ACG, calculated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. It supports the notion of a potential role of low CSFP in the pathogenesis of open-angle glaucoma.     

Effects of Thiazolidinedione Therapy on Inflammatory Markers of Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials

Background

Inflammation is a common feature in patients with type 2 diabetes mellitus (T₂DM). This meta-analysis aimed to assess the influence of thiazolidinedione (TZD) therapy on the circulating levels of inflammatory markers in patients with T₂DM.

Methods and Results

We searched the databases Medline, Embase, ScienceDirect, Web of Science, SpringerLink, and the Cochrane Library for randomized controlled trials (RCTs) that examined the effects of thiazolidinedione vs. a placebo on patients with T₂DM. The main outcomes were absolute changes in levels of circulating inflammatory markers. Twenty-seven RCTs were included and data were analyzed using a fixed-effect model or a random-effect model based on heterogeneity. Pooled results indicated that circulating levels of high-sensitivity C reactive protein (hsCRP; SMD = –0.65, 95% CI = –0.98 to –0.32, p < 0.01), monocyte chemoattractant protein-1 (MCP-1; WMD = –54.19, 95% CI = –73.86 to –34.52, p < 0.01), von Willebrand factor% (vWF%; WMD = –8.18, 95% CI = –13.54 to –2.81, p 0.01), fibrinogen (SMD = –0.26, 95% CI = –0.41 to –0.11, p < 0.01) and E-selectin(WMD = –3.57, 95% CI = –5.59 to -1.54, p <0.01) were significantly decreased after TZD therapy. However, interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble CD40 ligand, plasminogen activator inhibitor 1 (PAI-1) and intercellular adhesion molecule (ICAM-1) were not significantly affected. Subgroup analyses of PAI-1, vWF% and fibrinogen in terms of trial drugs showed significant reductions for rosiglitazone (all p valuses< 0.05), but not pioglitazone treatment. Conversely, the E-selectin (p < 0.01) lowering effect only existed in the pioglitazone group. Further, rosiglitazone and pioglitazone treatment reduced serum hsCRP and MCP-1 but had no marked effects on MMP-9, IL-6 and ICAM-1.

Conclusions

Limited evidence suggested that TZD therapy had anti-inflammatory property that might contribute to its beneficial effect on inflammatory state in patients with type 2 diabetes.     

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials

BackgroundThe risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.Methods and findingsWe searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available.From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I² 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267).Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I² 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I² 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results.Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I² 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I² 55%).A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.ConclusionsIn this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks.Study Registration: PROSPERO CRD42020163174

Mårten Alkmark and co-workers report on a meta-analysis of randomized trials of labour induction at 41 weeks'' gestation as compared with expectant management until 42 weeks.     

Importance of attributes and willingness to pay for oral anticoagulant therapy in patients with atrial fibrillation in China: A discrete choice experiment

BackgroundAdherence to oral anticoagulant therapy in patients with atrial fibrillation (AF) in China is low. Patient preference, one of the main reasons for discontinuation of oral anticoagulant therapy, is an unfamiliar concept in China.Methods and findingsA discrete choice experiment (DCE) was conducted to quantify patient preference on 7 attributes of oral anticoagulant therapy: antidote (yes/no), food–drug interaction (yes/no), frequency of blood monitoring (no need, every 6/3/1 month[s]), risk of nonfatal major bleeding (0.7/3.1/5.5/7.8[%]), risk of nonfatal stroke (ischemic/hemorrhagic) or systemic embolism (0.6/3.2/5.8/8.4[%]), risk of nonfatal acute myocardial infarction (AMI) (0.2/1.0/1.8/2.5[%]), and monthly out-of-pocket cost (0/120/240/360 RMB) (0 to 56 USD). A total of 16 scenarios were generated by using D-Efficient design and were randomly divided into 2 blocks. Eligible patients were recruited and interviewed from outpatient and inpatient settings of 2 public hospitals in Beijing and Shenzhen, respectively. Patients were presented with 8 scenarios and asked to select 1 of 3 options: 2 unlabeled hypothetical treatments and 1 opt-out option. Mixed logit regression model was used for estimating patients’ preferences of attributes of oral anticoagulants and willingness to pay (WTP) with adjustments for age, sex, education level, income level, city, self-evaluated health score, histories of cardiovascular disease/other vascular disease/any stroke/any bleeding, and use of anticoagulant/antiplatelet therapy. A total of 506 patients were recruited between May 2018 and December 2019 (mean age 70.3 years, 42.1% women). Patients were mainly concerned about the risks of AMI (β: −1.03; 95% CI: −1.31, −0.75; p < 0.001), stroke or systemic embolism (β: −0.81; 95% CI: −0.90, −0.73; p < 0.001), and major bleeding (β: −0.69; 95% CI: −0.78, −0.60; p < 0.001) and were willing to pay more, from up to 798 RMB to 536 RMB (124 to 83 USD) monthly. The least concerning attribute was frequency of blood monitoring (β: −0.31; 95% CI: −0.39, −0.24; p < 0.001). Patients had more concerns about food–drug interactions even exceeding preferences on the 3 risks, if they had a history of stroke or bleeding (β: −2.47; 95% CI: −3.92, −1.02; p < 0.001), recruited from Beijing (β: −1.82; 95% CI: −2.56, −1.07; p < 0.001), or men (β: −0.96; 95% CI: −1.36, −0.56; p < 0.001). Patients with lower educational attainment or lower income weighted all attributes lower, and their WTP for incremental efficacy and safety was minimal. Since the patients were recruited from 2 major hospitals from developed cities in China, further studies with better representative samples would be needed.ConclusionsPatients with AF in China were mainly concerned about the safety and effectiveness of oral anticoagulant therapy. The preference weighting on food–drug interaction varied widely. Patients with lower educational attainment or income levels and less experience of bleeding or stroke had more reservations about paying for oral anticoagulant therapies with superior efficacy, safety, and convenience of use.

In a discrete choice experiment, Jiaxi Zhao and colleagues investigate the importance of attributes of oral anticoagulant therapy and willingness-to-pay in patients with atrial fibrillation in China.     

Effects of APOA5 ?1131T>C (rs662799) on Fasting Plasma Lipids and Risk of Metabolic Syndrome: Evidence from a Case-Control Study in China and a Meta-Analysis

The apolipoprotein A5 (APOA5) gene −1131T>C (rs662799) has been suggested to be involved in the pathway of lipid homeostasis and the development of metabolic syndrome (MetS). However, the findings are not consistent. To systematically evaluate the associations between −1131T>C polymorphism and fasting lipid parameters and the risk of MetS, we conducted a case-control study in a Chinese population and a meta-analysis. The findings from 1840 Chinese participants indicated that the C allele carriers had significantly higher fasting total cholesterol (TC), triglycerides (TG) and lower HDL-cholesterol (HDL-C) than the TT homozygotes carriers. The −1131C allele was also found to be significantly associated with increased risk of MetS (OR  =  1.40, 95% confidence interval (CI)  =  1.15, 1.69) compared to the TT homozygotes. In the meta-analysis of 51,868 participants from 46 East Asian studies, 26 European studies and 19 studies of other ethnic groups, the −1131C allele was associated with higher fasting TC (weighted mean difference (WMD)  =  0.08 mmol/L, 95% CI  =  0.05, 0.10, P = 1.74×10⁻⁹), TG (WMD  =  0.30 mmol/L, 95% CI  =  0.26, 0.33, P =  1.87×10⁻⁵⁵), LDL-cholesterol (LDL-C) (WMD  =  0.04 mmol/L, 95% CI  =  0.02, 0.07, P = 0.002), and lower HDL-C (WMD  =  −0.05 mmol/L, 95% CI  =  −0.06,−0.04, P = 1.88×10⁻²¹), respectively. Based on 12 studies with 5,573 MetS cases and 8,290 controls from 5 East Asian studies, 5 European studies and 2 studies of other ethnic groups, the −1131C allele was associated with increased risk of MetS with an OR (95% CI)  =  1.33 (1.16, 1.53) in the overall population, 1.43 (1.29, 1.58) in East Asian and 1.30 (0.94, 1.78) in European populations. In conclusion, the −1131C allele may be associated with elevated levels of fasting TG, TC, LDL-C and decreased HDL-C, and increased risk of MetS, especially in East Asians.     

Therapeutic benefit of balneotherapy and hydrotherapy in the management of fibromyalgia syndrome: a qualitative systematic review and meta-analysis of randomized controlled trials

Introduction

In the present systematic review and meta-analysis, we assessed the effectiveness of different forms of balneotherapy (BT) and hydrotherapy (HT) in the management of fibromyalgia syndrome (FMS).

Methods

A systematic literature search was conducted through April 2013 (Medline via Pubmed, Cochrane Central Register of Controlled Trials, EMBASE, and CAMBASE). Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results

Meta-analysis showed moderate-to-strong evidence for a small reduction in pain (SMD −0.42; 95% CI [−0.61, −0.24]; P < 0.00001; I² = 0%) with regard to HT (8 studies, 462 participants; 3 low-risk studies, 223 participants), and moderate-to-strong evidence for a small improvement in health-related quality of life (HRQOL; 7 studies, 398 participants; 3 low-risk studies, 223 participants) at the end of treatment (SMD −0.40; 95% CI [−0.62, −0.18]; P = 0.0004; I² = 15%). No effect was seen at the end of treatment for depressive symptoms and tender point count (TPC).BT in mineral/thermal water (5 studies, 177 participants; 3 high-risk and 2 unclear risk studies) showed moderate evidence for a medium-to-large size reduction in pain and TPC at the end of treatment: SMD −0.84; 95% CI [−1.36, −0.31]; P = 0.002; I² = 63% and SMD −0.83; 95% CI [−1.42, −0.24]; P = 0.006; I² = 71%. After sensitivity analysis, and excluding one study, the effect size for pain decreased: SMD −0.58; 95% CI [−0.91, −0.26], P = 0.0004; I² = 0. Moderate evidence is given for a medium improvement of HRQOL (SMD −0.78; 95% CI [−1.13, −0.43]; P < 0.0001; I² = 0%). A significant effect on depressive symptoms was not found. The improvements for pain could be maintained at follow-up with smaller effects.

Conclusions

High-quality studies with larger sample sizes are needed to confirm the therapeutic benefit of BT and HT, with focus on long-term results and maintenance of the beneficial effects.     

ABCG5/G8 polymorphisms and markers of cholesterol metabolism: systematic review and meta-analysis

Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 ± 10.5 years; BMI, 23.9 ± 3.5 kg/m²). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant [n = 614; −0.11 mmol/l (95% CI, range: −0.20 to −0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best.     

Epidemiology of soil-transmitted helminth infections in Semarang,Central Java,Indonesia

Soil-transmitted helminth (STH) infections are endemic in Indonesia. However, prevalence data for many parts of the country are incomplete. The aim of this study was to determine human STH prevalence and knowledge and practices relating to STH risk behaviour, to provide a current view of the status of STH infection in rural communities in Central Java. A cross-sectional survey of 16 villages was conducted in Semarang, Central Java in 2015. Demographic and household data together with information about knowledge and practices relating to STH and hygiene were elicited through face-to-face interviews. Stool samples were collected and examined using the flotation method. Children (aged 2–12 years) also had their haemoglobin (Hb) levels, height and weight data collected, and BMI estimated. Data were analysed using univariate logistic regression analysis. A total of 6,466 individuals with a mean age of 33.5 years (range: 2–93) from 2,195 households were interviewed. The overall prevalence of STH was 33.8% with Ascaris lumbricoides (roundworm) the predominant nematode identified (prevalence = 26.0%). Hookworm and Trichuris trichiura (whipworm) were found in 7.9% and 1.8% of participants, respectively. Females were at increased odds of infection with A. lumbricoides (adjusted OR 1.14, 95% CI [1.02–1.29], p = 0.02). Adults in age groups 51–60 and over 60 years had the highest odds of being infected with hookworm (adjusted OR 3.01, 95% CI [1.84–4.91], p<0.001 and adjusted OR 3.79, 95% CI [2.30–6.26], p<0.001, respectively) compared to 6–12 year olds. Farmers also had higher odds of being infected with hookworm (adjusted OR 2.36, 95% CI [1.17–4.76], p = 0.02) compared to other occupation categories. Poverty (OR 2.14, 95% CI [1.77–2.58], p<0.001), overcrowding (OR 1.35, 95% CI [1.27–1.44], p<0.001), goat ownership (OR 1.61, 95% CI [1.10–2.41], p = 0.02) and the presence of dry floor space in the home (OR 0.73, 95% CI [0.58–0.91], p = 0.01) were all household factors significantly associated with an increased odds of infection. Infection with STH was not significantly associated with the gastrointestinal illness (p>0.05), BMI or Hb levels; however, one third of all 2–12 year olds surveyed were found to be anaemic (i.e. Hb concentrations below 110g/l or 115g/l for children under 5 and 5 years or older, respectively), with a greater proportion of school-age children at risk. Knowledge and behaviour related to hygiene and gastrointestinal diseases varied widely and were generally not associated with STH infection. The study revealed that STH infection remains endemic in Central Java despite ongoing deworming programs. Current control efforts would benefit from being re-evaluated to determine a more effective way forward.     

Diabetic Retinopathy and Estimated Cerebrospinal Fluid Pressure. The Beijing Eye Study 2011

Purpose

The cerebrospinal fluid pressure (CSFP) is a major determinant of central retinal vein pressure and thus of retinal capillary pressure. We tested the hypothesis whether prevalence and severity of diabetic retinopathy are associated with CSFP.

Methods

The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. A detailed ophthalmic examination was performed including fundus photography for the assessment of diabetic retinopathy according. Based on a previous study with lumbar cerebrospinal fluid pressure (CSFP) measurements, CSFP was calculated as CSFP[mmHg] = 0.44xBody Mass Index[kg/m²]+0.16 Diastolic Blood Pressure[mmHg]–0.18xAge[Years]−1.91.

Results

In binary regression analysis, presence of diabetic retinopathy was significantly associated with higher levels of HbA1c (P<0.001; regression coefficient B:0.25; odds ratio (OR):1.28; 95% confidence interval (CI):1.15,1.43), higher blood concentration of glucose (P<0.001; B:0.40;OR:1.49;95%CI:1.36,1.63), longer known duration of diabetes mellitus (P<0.001; B:0.14;OR:1.15; 95%CI:1.11,1.19), higher systolic blood pressure (P<0.001; B:0.03;OR:1.03;95%CI:1.02,1.04), lower diastolic blood pressure (P<0.001; B:−0.06;OR:0.94;95%CI:0.91,0.97), and higher CSFP (P = 0.002; B:0.13;OR:1.14;95%CI:1.05,1.24). Severity of diabetic retinopathy was significantly associated with higher HbA1c value (P<0.001; standardized coefficient beta: 0.19; correlation coefficient B: 0.07;95%CI:0.05,0.08), higher blood concentration of glucose (P<0.001; beta:0.18;B:0.04;95%CI:0.04,0.05), longer known duration of diabetes mellitus (P<0.001; beta:0.20;B:0.03;95%CI:0.02,0.03), lower level of education (P = 0.001; beta:−0.05;B:−0.02;95%CI:−0.03,−0.01), lower diastolic blood pressure (P = 0.002; beta:−0.08;B:−0.001;95%CI:−0.004,−0.001), higher systolic blood pressure (P = 0.006; beta:0.06;B:0.001;95%CI:0.000,0.001), and higher CSFP (P = 0.006; beta:0.06;B:0.006;95%CI:0.002,0.010).

Conclusions

Higher prevalence and severity of diabetic retinopathy were associated with higher estimated CSFP after adjusting for systemic parameters. Higher CSFP through a higher retinal vein pressure may lead to more marked retinal venous congestion and vascular leakage in diabetic retinae.     

The Mpumalanga Men's Study (MPMS): Results of a Baseline Biological and Behavioral HIV Surveillance Survey in Two MSM Communities in South Africa

The Mpumalanga Men''s Study (MPMS) is the assessment of the Project Boithato HIV prevention intervention for South African MSM. Boithato aims to increase consistent condom use, regular testing for HIV-negative MSM, and linkage to care for HIV-positive MSM. The MPMS baseline examined HIV prevalence and associated risk behaviors, and testing, care, and treatment behaviors among MSM in Gert Sibande and Ehlanzeni districts in Mpumalanga province, South Africa in order to effectively target intervention activities. We recruited 307 MSM in Gert Sibande and 298 in Ehlanzeni through respondent-driven sampling (RDS) between September 2012-March 2013. RDS-adjusted HIV prevalence estimates are 28.3% (95% CI 21.1%–35.3%) in Gert Sibande, and 13.7% (95% CI 9.1%–19.6%) in Ehlanzeni. Prevalence is significantly higher among MSM over age 25 [57.8% (95% CI 43.1%–72.9%) vs. 17.9% (95% CI 10.6%–23.9%), P<0.001 in Gert Sibande; 34.5% (95%CI 20.5%–56.0%) vs. 9.1% (95% CI 4.6%–13.9%), P<0.001 in Ehlanzeni]. In Gert Sibande, prevalence is higher among self-identified gay and transgender MSM vs. other MSM [39.3% (95%CI, 28.3%–47.9%), P<0.01], inconsistent condom users [38.1% (18.1%–64.2%), P<0.05], those with a current regular male partner [35.0% (27.1%–46.4%), P<0.05], and those with lifetime experience of intimate partner violence with men [40.4%, (95%CI 28.9%–50.9%), P<0.05]. Prevalence of previous HIV testing was 65.8% (95%CI 58.8%–74.0%) in Gert Sibande, and 69.3% (95%CI 61.9%–76.8%) in Ehlanzeni. Regular HIV testing was uncommon [(34.6%, (95%CI 27.9%–41.4%) in Gert Sibande; 31.0% (95%CI 24.9%–37.8%) in Ehlanzeni]. Among HIV-positive participants, few knew their status (28.1% in Gert Sibande and 14.5% in Ehlanzeni), or were appropriately linked to care (18.2% and 11.3%, respectively), or taking antiretroviral therapy (13.6% and 9.6% respectively). MPMS results demonstrate the importance of implementing interventions for MSM to increase consistent condom use, regular HIV testing, and linkage and engagement in care for HIV-infected MSM.     

Five-Year Change in Intraocular Pressure Associated with Changes in Arterial Blood Pressure and Body Mass Index. The Beijing Eye Study

Purpose

To examine a potential association between longitudinal changes in intraocular pressure (IOP), arterial blood pressure and body mass index (BMI) in a population-based setting.

Methods

The longitudinal population-based Beijing Eye Study included 2355 subjects with an age of 45+ years who were examined in 2006 and in 2011. The participants underwent a detailed ophthalmic examination including tonometry and measurement of arterial blood pressure and BMI.

Results

Data on IOP, arterial blood pressure and BMI measured in 2006 and in 2011 were available for 2257 (95.8%) subjects with a mean age of 59.5±9.7 years. The mean change in IOP was −1.25±2.26 mm Hg, mean change in mean blood pressure −7.4±12.1 mmHg, and mean change in BMI was 0.01±2.04 kg/m². In multivariate analysis, the 5-year change in IOP was significantly associated with a higher change in mean blood pressure (P<0.001; standardized regression coefficient Beta:0.11; regression coefficient B:0.02; 95% confidence interval (CI):0.01,0.03) after adjusting for younger age (P<0.001;Beta:−0.18;B:−0.04;95% CI:−0.05,−0.03), shorter body stature (P = 0.002;Beta:−0.06;B:−0.06;95% CI:−0.03,−0.01), thicker central corneal thickness (P<0.001;Beta:0.19;B:0.02;95% CI:0.01,0.02), deeper anterior chamber depth (P = 0.01;Beta:0.05;B:0.33;95% CI:0.07,0.60), and lower intraocular pressure at baseline (P<0.001;Beta:−0.56;B:−0.42;95% CI:−0.45,−0.39). If the analysis included only longitudinal parameters, the change in IOP was significantly associated with a higher change in mean arterial blood pressure (P<0.001;Beta:0.10;B:0.02;95% CI:0.01,0.03) and a higher change in body mass index (P<0.04;Beta:0.04;B:0.04;95% CI:0.01,0.09).

Conclusions

In the 5-year follow-up of our population-based sample, a change in IOP was associated with a corresponding change in arterial blood pressure and with a corresponding change in body mass index. These longitudinal data support the notion of a physiological relationship between arterial blood pressure, intraocular pressure and body mass index. These findings may be of interest for the discussion of the pathogenesis of glaucomatous optic neuropathy.     

Aliskiren and Amlodipine in the Management of Essential Hypertension: Meta-Analysis of Randomized Controlled Trials

Background

Aliskiren is a novel renin-angiotensin aldosterone system (RAAS) inhibitor, the combination therapy of aliskiren and amlodipine for blood pressure control have been reported recently. The primary objective of this analysis is to review recently reported randomized controlled trials (RCTs) to compare antihypertensive effects and adverse events between mono (amlodipine or aliskiren alone) and combination therapy of both medicines.

Methods

Databases for the search included Pubmed, Embase and the Cochrane Central Register of Controlled Trials. Revman v5.0 statistical program was used to analyze the data. Weighted mean differences (WMD) with a 95% confidence interval (CI) were used for the calculation of continuous data, and relative risk (RR) with a 95% CI was used for dichotomous data.

Results

We analyzed the data from 7 RCTs for a total of 6074 participants in this meta-analysis. We found that the aliskiren/amlodipine combination therapy had a stronger effect in lowering blood pressure as compared with the monotherapy using aliskiren (SBP: WMD = −10.42, 95% CI −13.03∼−7.82, P<0.00001; DBP: WMD = −6.60, 95% CI −7.22∼−5.97, P<0.00001) or amlodipine (SBP: WMD = −4.85, 95% CI −6.88∼−2.81, P<0.00001; DBP: WMD = −2.91, 95% CI −3.85∼−1.97, P<0.00001). No differences were found in terms of adverse events between combination therapy and monotherapy, except for the rates of peripheral edema and hypokalaemia which were significantly lower in the combination therapy than in the amlodipine monotherapy (RR = 0.78, 0.66∼0.92, P = 0.004; RR = 0.51, 0.27∼0.97, P = 0.04). Similar antihypertensive effects were found in both obese (body mass index > = 30 kg/m²) hypertensive and non-obese (body mass index <30 kg/m²) hypertensive patients. Moreover, there was no difference with the blood pressure lowering or adverse effects with regards to the combination therapy in both subgroups.

Conclusion

We found that aliskiren/amlodipine combination therapy provided a more effective blood pressure reduction than monotherapy with either drug without increase in the occurrence of adverse events.