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Annals of Palliative Medicine Oct 2022Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of blosozumab versus placebo in perimenopausal and postmenopausal women.
METHODS
This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "blosozumab" to retrieve studies on the relationship between blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC).
RESULTS
Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P<0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis.
CONCLUSIONS
The results suggested that blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.
Topics: Female; Humans; Middle Aged; Bone Density Conservation Agents; Osteocalcin; Osteoporosis; Osteoporosis, Postmenopausal; Postmenopause; Randomized Controlled Trials as Topic
PubMed: 36367007
DOI: 10.21037/apm-22-998 -
Frontiers in Medicine 2022Hepatic fibrosis is a health challenge due to the absence of satisfactory therapy, especially at the cirrhosis stage. Dahuang Zhechong pill (DHZCP)-based therapy is...
BACKGROUND
Hepatic fibrosis is a health challenge due to the absence of satisfactory therapy, especially at the cirrhosis stage. Dahuang Zhechong pill (DHZCP)-based therapy is reportedly a successful treatment for hepatic fibrosis and is even beneficial for the treatment of cirrhosis. Hence, a systematic review and clinical evidence assessment of DHZCP-based therapy should be performed, and clinical recommendations based on its efficacy for the treatment of hepatic fibrosis should be generated. With respect to potential indicators, the comparative value of the hepatic function, spleen thickness, and portal vein internal diameter should be evaluated.
MATERIALS AND METHODS
PubMed, the Excerpta Medica Database, the Cochrane Library, the Web of Science, the WanFang Database, the Chinese Scientific Journal Database, and the Chinese National Knowledge Infrastructure database were searched to identify clinical trials. Three subgroup analyses were performed based on the stage of disease, medication use, and the course of treatment. Statistical analyses were performed using Review Manager 5.4.
RESULTS
A total of 18 studies including 1,494 patients were evaluated. The DHZCP-based therapy was effective in reducing the plasma levels of hyaluronic acid, and laminin, procollagen III, and IV collagen were also reduced irrespective of the hepatitis stage or the presence of hepatic cirrhosis. Abnormalities in alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin were reversed. A 6-month course of treatment was the most beneficial DHZCP-based therapy regimen. Alanine aminotransferase improvement was more obvious in patients with cirrhosis, and alanine aminotransferase was reduced significantly in patients with hepatic cirrhosis. With respect to pharmacological mechanisms, DHZCP-based therapy could inhibit hepatic stellate cell growth and activation, reduce inflammation, and prevent extracellular matrix formation. Hepatic portal hypertension and splenomegaly were ameliorated significantly in the DHZCP-based therapy group.
CONCLUSION
Dahuang Zhechong pill-based therapy has demonstrated efficacy as a treatment for hepatic fibrosis and cirrhosis. A 6-month course of treatment is the recommended option for DHZCP-based therapy in clinical practice. The combination of DHZCP-based therapy and entecavir is a favorable treatment for hepatic cirrhosis.
PubMed: 36314011
DOI: 10.3389/fmed.2022.920062 -
Journal of Clinical Medicine Jun 2019This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis... (Review)
Review
This study seeks to evaluate the long-term effects of pharmacologic therapy on the bone markers and bone mineral density of transgender patients and to provide a basis for understanding its potential implications on therapies involving implant procedures. Following the referred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and well-defined PICOT (Problem/Patient/Population, Intervention, Comparison, Outcome, Time) questionnaires, a literature search was completed for articles in English language, with more than a 3 year follow-up reporting the long-term effects of the cross-sex pharmacotherapy on the bones of adult transgender patients. Transgender demographics, time under treatment, and treatment received were recorded. In addition, bone marker levels (calcium, phosphate, alkaline phosphatase, and osteocalcin), bone mineral density (BMD), and bone turnover markers (Serum Procollagen type I N-Terminal pro-peptide (PINP), and Serum Collagen type I crosslinked C-telopeptide (CTX)) before and after the treatment were also recorded. The considerable variability between studies did not allow a meta-analysis. All the studies were completed in European countries. Transwomen (921 men to female) were more frequent than transmen (719 female to male). Transwomen's treatments were based in antiandrogens, estrogens, new drugs, and sex reassignment surgery, meanwhile transmen's surgeries were based in the administration of several forms of testosterone and sex reassignment. Calcium, phosphate, alkaline phosphatase, and osteocalcin levels remained stable. PINP increased in transwomen and transmen meanwhile, CTX showed contradictory values in transwomen and transmen. Finally, reduced BMD was observed in transwomen patients receiving long-term cross-sex pharmacotherapy. Considering the limitations of this systematic review, it was concluded that long-term cross-sex pharmacotherapy for transwomen and transmen transgender patients does not alter the calcium, phosphate, alkaline phosphatase, and osteocalcin levels, and will slightly increase the bone formation in both transwomen and transmen patients. Furthermore, long-term pharmacotherapy reduces the BMD in transwomen patients.
PubMed: 31159456
DOI: 10.3390/jcm8060784 -
Bone Feb 2021Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs).... (Review)
Review
BACKGROUND
Bone turnover is the cellular machinery responsible for bone integrity and strength and, in the clinical setting, it is assessed using bone turnover markers (BTMs). Acute exercise can induce mechanical stress on bone which is needed for bone remodelling, but to date, there are conflicting results in regards to the effects of varying mechanical stimuli on BTMs.
OBJECTIVES
This systematic review examines the effects of acute aerobic, resistance and impact exercises on BTMs in middle and older-aged adults and examines whether the responses are determined by the exercise mode, intensity, age and sex.
METHODS
We searched PubMed, SCOPUS, Web of Science and EMBASE up to 22nd April 2020. Eligibility criteria included randomised controlled trials (RCTs) and single-arm studies that included middle-aged (50 to 65 years) and older adults (>65 years) and, a single-bout, acute-exercise (aerobic, resistance, impact) intervention with measurement of BTMs. PROSPERO registration number CRD42020145359.
RESULTS
Thirteen studies were included; 8 in middle-aged (n = 275, 212 women/63 men, mean age = 57.9 ± 1.5 years) and 5 in older adults (n = 93, 50 women/43 men, mean age = 68.2 ± 2.2 years). Eleven studies included aerobic exercise (AE, 7 middle-aged/4 older adults), and two included resistance exercise (RE, both middle-aged). AE significantly increased C-terminal telopeptide (CTX), alkaline phosphatase (ALP) and bone-ALP in middle-aged and older adults. AE also significantly increased total osteocalcin (tOC) in middle-aged men and Procollagen I Carboxyterminal Propeptide and Cross-Linked Carboxyterminal Telopeptide of Type I Collagen in older women. RE alone decreased ALP in older adults. In middle-aged adults, RE with impact had no effect on tOC or BALP, but significantly decreased CTX. Impact (jumping) exercise alone increased Procollagen Type 1 N Propeptide and tOC in middle-aged women.
CONCLUSION
Acute exercise is an effective tool to modify BTMs, however, the response appears to be exercise modality-, intensity-, age- and sex-specific. There is further need for higher quality and larger RCTs in this area.
Topics: Aged; Alkaline Phosphatase; Biomarkers; Bone Density; Bone Remodeling; Collagen Type I; Exercise; Female; Humans; Male; Middle Aged; Peptide Fragments; Procollagen
PubMed: 33227507
DOI: 10.1016/j.bone.2020.115766 -
BMC Musculoskeletal Disorders Nov 2022Both denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both denosumab and bisphosphonates have been demonstrated effective for glucocorticoid-induced osteoporosis. However, evidence-based medicine is still lacking to prove the clinical results between denosumab and bisphosphonates. This meta-analysis aims to compare the efficacy and safety between denosumab and oral bisphosphonates for the treatment of glucocorticoid-induced osteoporosis through evidence-based medicine.
METHODS
MEDLINE, EMBASE, and the Cochrane library databases were searched up to June 2022 for randomized controlled trials that compared denosumab and oral bisphosphonates in the treatment of glucocorticoid-induced osteoporosis. The following outcomes were extracted for comparison: percentage change in bone mineral density from baseline at the lumbar spine, total hip, femoral neck, and ultra-distal radius; percentage change from baseline in serum concentration of bone turnover markers; and incidence of treatment-emergent adverse events.
RESULTS
Four randomized controlled trials involving 714 patients were included. The pooled results showed that denosumab was superior to bisphosphonates in improving bone mineral density in lumbar spine (mean difference (MD) 1.70; 95% confidence interval (CI) 1.11-2.30; P < 0.001) and ultra-distal radius (MD 0.87; 95% CI 0.29-1.45; P = 0.003), and in suppressing C-terminal telopeptide of type 1 collagen (MD -34.83; 95% CI -67.37--2.28; P = 0.04) and procollagen type 1 N-terminal propeptide (MD -14.29; 95% CI -23.65- -4.94; P = 0.003) at 12 months. No significant differences were found in percentage change in total hip or femoral neck bone mineral density at 12 months, or in the incidence of treatment-emergent adverse events or osteoporosis-related fracture.
CONCLUSIONS
Compared with bisphosphonates, denosumab is superior in improving bone mineral density in lumbar spine and ultra-distal radius for glucocorticoid-induced osteoporosis. Further studies are needed to prove the efficacy of denosumab.
Topics: Humans; Bone Density; Denosumab; Diphosphonates; Glucocorticoids; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic
PubMed: 36447169
DOI: 10.1186/s12891-022-05997-0 -
Frontiers in Medicine 2023Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the...
Treatment of liver fibrosis in hepatolenticular degeneration with traditional Chinese medicine: systematic review of meta-analysis, network pharmacology and molecular dynamics simulation.
BACKGROUND
Traditional Chinese medicine (TCM) is widely used in the clinical treatment of hepatolenticular degeneration (HLD) and liver fibrosis (LF). In the present study, the curative effect was assessed using meta-analysis. The possible mechanism of TCM against LF in HLD was investigated using network pharmacology and molecular dynamics simulation.
METHODS
For literature collection, we searched several databases, including PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI), VIP Database for Chinese Technical Periodicals (VIP) and Wan Fang database until February 2023, and the Review Manager 5.3 was used to analyze the data. Network pharmacology and molecular dynamics simulation were used to explore the mechanism of TCM in treating LF in HLD.
RESULTS
The results of the meta-analysis revealed that the addition of Chinese herbal medicine (CHM) in treating HLD resulted in a higher total clinical effective rate than western medicine alone [RR 1.25, 95% CI (1.09, 1.44), = 0.002]. It not only has a better effect on liver protection [Alanine aminotransferase: SMD = -1.20, 95% CI (-1.70, -0.70), < 0.00001; Aspartate aminotransferase: SMD = -1.41, 95% CI (-2.34, -0.49), = 0.003; Total bilirubin: SMD = -1.70, 95% CI (-3.36, -0.03), = 0.05] but also had an excellent therapeutic effect on LF through four indexes [Hyaluronic acid: SMD = -1.15, 95% CI (-1.76, -0.53), = 0.0003; Procollagen peptide III: SMD = -0.72, 95% CI (-1.29, -0.15), = 0.01; Collagen IV: SMD = -0.69, 95% CI (-1.21, -0.18), = 0.008; Laminin: SMD = -0.47, 95% CI (-0.95, 0.01), = 0.06]. Concurrently, the liver stiffness measurement decreased significantly [SMD = -1.06, 95% CI (-1.77, -0.36), = 0.003]. The results of network pharmacological experiments and molecular dynamics simulation indicate that the three high-frequency TCMs (Rhei Radix Et Rhizoma-Coptidis Rhizoma-Curcumae Longae Rhizoma, DH-HL-JH) primarily act on the core targets (AKT1, SRC, and JUN) via the core components (rhein, quercetin, stigmasterol, and curcumin), regulate the signal pathway (PI3K-Akt, MAPK, EGFR, and VEGF signaling pathways), and play a role of anti-LF.
CONCLUSION
Meta-analysis indicates that TCM is beneficial in treating HLD patients and improving LF. The present study successfully predicts the effective components and potential targets and pathways involved in treating LF for the three high-frequency CHMs of DH-HL-JH. The findings of the present study are hoped to provide some evidence support for clinical treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022302374.
PubMed: 37250630
DOI: 10.3389/fmed.2023.1193132 -
European Journal of Clinical... Oct 2023The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised... (Meta-Analysis)
Meta-Analysis Review
AIM
The effects of vitamin D administration on bone turnover markers (BTMs) in adults are controversial. Thus, we carried out a meta-analysis of available randomised controlled trials (RCTs) to examine the impact of vitamin D supplementation on BTMs.
METHODS
To identify relevant RCTs, we searched the PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library and Embase databases for manuscripts published up to July 2022. The present study was conducted in agreement with the PRISMA guidelines. Weighed mean difference (WMD) and 95% confidence intervals (CI) were used to calculate the magnitude of the effect of the intervention.
RESULTS
A total of 42 RCTs were included in the meta-analysis. The age of the participants enrolled in the RCTs ranged from 19.4 to 84 years. The pooled results depicted a decrease in deoxypyridinoline (DPD) concentrations (WMD: -1.58 nmol/mmol, 95% CI: -2.55, -.61, p = .001) following vitamin D supplementation. In addition, subgroup analyses demonstrated that vitamin D administration notably reduced procollagen type I N-terminal propeptide (PINP) levels in individuals aged >50 years and led to a pronounced decrease in alkaline phosphatase (ALP) values when the intervention lasted >12 weeks. No significant effect was observed on other BTMs, for example, collagen type 1 cross-linked C-telopeptide (CTX) and osteocalcin (OC) levels.
CONCLUSION
Vitamin D administration decreases DPD, PINP and ALP levels, indicating a reduced bone turnover following the intervention. Other BTMs, for example, CTX or OC values, were not affected by vitamin D prescription. Vitamin D supplementation may exert a positive effect on some important BTMs.
Topics: Adult; Humans; Vitamin D; Collagen Type I; Bone Remodeling; Alkaline Phosphatase; Biomarkers; Osteocalcin; Dietary Supplements; Randomized Controlled Trials as Topic
PubMed: 37314058
DOI: 10.1111/eci.14038 -
Journal of Traditional Chinese Medicine... Jun 2023To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease: a systematic review and Meta-analysis.
OBJECTIVE
To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine (TCM) for managing renal fibrosis (RF) in patients with chronic kidney disease (CKD).
METHODS
We searched randomized controlled trials (RCTs) from eight databases.
RESULTS
Sixteen eligible studies with 1,356 participants were included in this study. Compared to treatment with Western Medicine (WM) alone, the combined treatment with activating blood circulation and removing blood stasis in terms of TCM (ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen (CⅣ) (: 2.17, 95% : 3.01 to 1.34), type Ⅲ procollagen (PCⅢ) (: 1.08, 95% : 1.64 to 0.53), laminin (LN) (: 1.28, 95% : 1.65 to 0.90), transforming growth factor β 1 (TGFβ1) (: 0.65, 95% : 1.18 to 0.12), serum creatinine (Scr) (: 1.36, 95% : 1.85 to 0.87), blood urea nitrogen (BUN) (: 1.51, 95% : 2.59 to 0.43), and 24 h urine protein (24hUpro) (: 1.23; 95% : 1.96 to 0.50). The level of hyaluronic acid (HA) was similar in both types of treatment (: 0.74, 95% : 1.91 to 0.44). The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ, PC-Ⅲ, and LN (<0.05). The effectiveness of the longer duration to C-Ⅳ, PC-Ⅲ, and LN was not certain. However, the result should be interpreted in care. The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects. The results of the Metaanalysis were not stable enough. There was publication bias for the reports on Scr ( 0.001), C-Ⅳ ( 0.001), PC-Ⅲ ( 0.026), and LN ( 0.030) and no publication bias for the reports on BUN ( 0.293). The quality of evidence varied from low to very low.
CONCLUSIONS
The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone. Highquality RCTs need to be conducted for the strong support.
Topics: Humans; Medicine, Chinese Traditional; Drugs, Chinese Herbal; Renal Insufficiency, Chronic; Phytotherapy; Fibrosis
PubMed: 37147744
DOI: 10.19852/j.cnki.jtcm.20230308.003 -
Endocrine Jan 2018In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH... (Meta-Analysis)
Meta-Analysis Review
Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis.
PURPOSE
In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear.
METHODS
We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible.
RESULTS
We included eight studies. Seven randomized 272 post-menopausal women, 61-69 years, to GH or control, for 6-24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = -0.01 [-0.04, 0.02]), total hip (WMD = 0 [-0.05, 0.06]) or femoral neck (WMD = 0 [-0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention.
CONCLUSION
GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.
Topics: Aged; Bone Density; Female; Fractures, Bone; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hypopituitarism; Middle Aged; Osteoporosis; Osteoporotic Fractures; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 29030774
DOI: 10.1007/s12020-017-1440-0 -
Journal of the American Heart... Oct 2015There has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF).... (Meta-Analysis)
Meta-Analysis Review
Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta-Analysis and Systematic Review.
BACKGROUND
There has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta-analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF.
METHODS & RESULTS
Randomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e', a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy-terminal peptide of procollagen type I [PICP] and amino-terminal peptide of pro-collagen type-II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e' (weighted mean difference [WMD] [95% confidence interval {CI}]: -1.68 [-2.03 to -1.33]; P<0.0001) and deceleration time (WMD [95% CI]: -12.0 ms [-23.3 to -0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions.
CONCLUSION
MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.
Topics: Chi-Square Distribution; Diastole; Fibrosis; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Recovery of Function; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling
PubMed: 26459931
DOI: 10.1161/JAHA.115.002137