Proprotein Convertase Subtilisin/Kexin Type 9 Gene Variants in Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis

Proprotein Convertase Subtilisin Kexin type 9 (PCSK9), comprises 12 exons, encoded for an enzyme which plays a critical role in the regulation of circulating low density lipoprotein. The gain-of-function (GOF) mutations aggravate the degradation of LDL receptors, resulting in familial hypercholesterolemia (FH), while loss-of-function (LOF) mutations lead to higher levels of the LDL receptors, lower the levels of LDL cholesterol, and preventing from cardiovascular diseases. It is noted that, previous publications related to the mutations of PCSK9 were not always unification. Therefore, this study aims to present the spectrum and distribution of PCSK9 gene mutations by a meta-analysis. A systematic literature analysis was conducted based on previous studies published by using different keywords. The weighted average frequency of PCSK9 mutation was calculated and accessed by MedCalc®. A total of 32 cohort studies, that included 19,725 familial hypercholesterolemia blood samples, were enrolled in the current study. The analysis results indicated that, based on the random-effect model, the weighted prevalence of PCSK9 mutation was 5.67% (95%CI = 3.68–8.05, p < 0.0001). The prevalence of PCSK9 GOF mutations was 3.57% (95%CI = 1.76–5.97, p < 0.0001) and PCSK9 LOF mutations was 6.05% (95%CI = 3.35–9.47, p < 0.0001). Additionally, the first and the second exon were identified as the hot spot of mutation occurred in PCSK9. Both GOF and LOF mutations have a higher proportion in Asia and Africa compared with other regions. The GOF PCSK9 p.(Glu32Lys) and LOF PCSK9 p.(Leu21dup/tri) were dominant in the Asia region with the proportion as 6.58% (95%CI = 5.77–7.47, p = 0.62) and 16.20% (95%CI = 6.91–28.44, p = 0.0022), respectively. This systematic analysis provided scientific evidence to suggest the mutation of PCSK9 was related to the metabolism of lipoprotein and atherosclerotic cardiovascular disease.

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Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.758956 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiahui Liu ◽

Fangfang Fan ◽

Xingyu Luo ◽

Wenjun Ji ◽

Yaokun Liu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Positive Association ◽

Systemic Review ◽

Proprotein Convertase ◽

Pcsk9 Inhibitors ◽

Clinical Role ◽

Increased Risk

Background: A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). However, whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear.Methods: We conducted a meta-analysis to investigate the ability of PCSK9 concentrations to predict future CV events in patients with established CVD. A comprehensive search of electronic databases was conducted in June 2021. We included relative risk (RR) estimates with 95% CI or events of interest.Results: Eleven cohort studies including 8,471 patients with CVD were enrolled. The pooled RR of CV events for the increase in the circulating baseline PCSK9 concentrations by 1 SD showed a positive association in a random-effect model (RR 1.226, 95% CI: 1.055–1.423, P = 0.008). Similarly, the risk of the total CV events increased by 52% in the patients in the highest tertile compared with those in the lowest tertile of circulating PCSK9 concentrations (RR 1.523, 95% CI: 1.098–2.112, P = 0.012). The association between PCSK9 and CV events was stronger in stable patients with CVD, patients treated with statins, and Asian patients.Conclusions: High PCSK9 concentrations are significantly related to the increased risk of future CV events. These results enrich the knowledge of PCSK9 function and suggest the further possible clinical role of PCSK9 inhibitors.

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Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: a systematic review and meta-analysis

Heart ◽

10.1136/heartjnl-2019-314763 ◽

2019 ◽

pp. heartjnl-2019-314763 ◽

Cited By ~ 4

Author(s):

Heyue Du ◽

Xiaodan Li ◽

Na Su ◽

Ling Li ◽

Xiaoting Hao ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Baseline Risk ◽

Major Adverse Cardiovascular Events ◽

Control Group ◽

Proprotein Convertase ◽

Pcsk9 Inhibitors ◽

Quality Evidence

BackgroundTo evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE).MethodsOur systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence.ResultsWe included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence.ConclusionsThis study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke.Trial registrationPROSPERO; CRD42017073904.

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Spatial Evolution and Critical Factors of Urban Innovation: Evidence from Shanghai, China

Sustainability ◽

10.3390/su12030938 ◽

2020 ◽

Vol 12 (3) ◽

pp. 938

Author(s):

Lingyue Li ◽

Xiaohu Zhang

Keyword(s):

Hot Spot ◽

Critical Role ◽

Random Effect ◽

Random Effect Model ◽

Urban China ◽

Spatial Evolution ◽

Critical Factors ◽

Methodological Innovation ◽

Strong Concentration ◽

Innovation Activities

The critical role of urban innovation in sustaining urban economic resilience has been widely acknowledged by scholars. Yet there is far from a full spectrum of understanding about how innovation performs, despite China’s innovation outputs having far outweighed most countries’. The perennial concern regarding the spatial patterns of innovation has been biased towards the macroscale, and long-standing efforts to explore the determinants of innovative vitality are focused on internal factors (e.g., research and development activities, and firm size). Considering these inadequacies, this research investigates how innovative activities are spatially distributed and how the pattern evolves in cities at the microscale, and examines influencing factors of the external environment. The patent data from 2000 to 2015 in Shanghai are geocoded and mapped into 1 km2 hexagon grids to identify local clustering. Gini coefficient is computed to show the high concentration of innovation activities across space. The hot spot analysis based on the Getis–Ord (Gi*) statistic shows that innovation exhibits a strong concentration propensity at the microscale and gradually moves toward a polycentric pattern. However, the extent of concentration decreases over the study period. Firms dictate innovation activities, and individuals and universities also play a role in downtown innovation growth. The regression using random effect model shows heterogeneous effects on different innovation actors. The overall urban innovation output, dominated by firms, is significantly influenced by public budget expenditures and green space areas. The science and technology grant has a positive impact on authorities but not university and research institutes. This research not only contributes to a methodological innovation for measuring and visualizing an innovation pattern but also enriches our understanding of spatial evolution and critical factors of innovation activities in urban China.

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Prevalence and risk factors for antibiotic utilization in Chinese children

BMC Pediatrics ◽

10.1186/s12887-021-02706-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shasha Guo ◽

Qiang Sun ◽

Xinyang Zhao ◽

Liyan Shen ◽

Xuemei Zhen

Keyword(s):

Risk Factors ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Healthcare Research ◽

Chinese Children ◽

Rural Setting ◽

Antibiotic Prescribing ◽

Antibiotic Utilization ◽

At Home

Abstract Background Antibiotic resistance poses a significant threat to public health globally. Irrational utilization of antibiotics being one of the main reasons of antibiotic resistant. Children as a special group, there's more chance of getting infected. Although most of the infection is viral in etiology, antibiotics still are the most frequently prescribed medications for children. Therefore, high use of antibiotics among children raises concern about the appropriateness of antibiotic prescribing. This systematic review aims to measuring prevalence and risk factors for antibiotic utilization in children in China. Methods English and Chinese databases were searched to identify relevant studies evaluating the prevalence and risk factors for antibiotic utilization in Chinese children (0-18 years), which were published between 2010 and July 2020. A Meta-analysis of prevalence was performed using random effect model. The Agency for Healthcare Research and Quality (AHRQ) and modified Jadad score was used to assess risk of bias of studies. In addition, we explored the risk factors of antibiotic utilization in Chinese children using qualitative analysis. Results Of 10,075 studies identified, 98 eligible studies were included after excluded duplicated studies. A total of 79 studies reported prevalence and 42 studies reported risk factors for antibiotic utilization in children. The overall prevalence of antibiotic utilization among outpatients and inpatients were 63.8% (35 studies, 95% confidence interval (CI): 55.1-72.4%), and 81.3% (41 studies, 95% CI: 77.3-85.2%), respectively. In addition, the overall prevalence of caregiver’s self-medicating of antibiotics for children at home was 37.8% (4 studies, 95% CI: 7.9-67.6%). The high prevalence of antibiotics was associated with multiple factors, while lacking of skills and knowledge in both physicians and caregivers was the most recognized risk factor, caregivers put pressure on physicians to get antibiotics and self-medicating with antibiotics at home for children also were the main factors attributed to this issue. Conclusion The prevalence of antibiotic utilization in Chinese children is heavy both in hospitals and home. It is important for government to develop more effective strategies to improve the irrational use of antibiotic, especially in rural setting.

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A meta-analysis comparing short-term weight and cardiometabolic changes between olanzapine/samidorphan and olanzapine

Scientific Reports ◽

10.1038/s41598-021-87285-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Manit Srisurapanont ◽

Sirijit Suttajit ◽

Surinporn Likhitsathian ◽

Benchalak Maneeton ◽

Narong Maneeton

Keyword(s):

Weight Gain ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Dropout Rates ◽

Lower Percentage ◽

Current Evidence ◽

Weight Changes ◽

Short Term ◽

Short Term Treatment

AbstractThis study compared weight and cardiometabolic changes after short-term treatment of olanzapine/samidorphan and olanzapine. Eligible criteria for an included trial were ≤ 24 weeks, randomized controlled trials (RCTs) that compared olanzapine/samidorphan and olanzapine treatments in patients/healthy volunteers and reported weight or cardiometabolic outcomes. Three databases were searched on October 31, 2020. Primary outcomes included weight changes and all-cause dropout rates. Standardized mean differences (SMDs) and risk ratios (RRs) were computed and pooled using a random-effect model. This meta-analysis included four RCTs (n = 1195). The heterogeneous data revealed that weight changes were not significantly different between olanzapine/samidorphan and olanzapine groups (4 RCTs, SDM = − 0.19, 95% CI − 0.45 to 0.07, I2 = 75%). The whole-sample, pooled RR of all-cause dropout rates (4 RCTs, RR = 1.02, 95% CI 0.84 to 1.23, I2 = 0%) was not significant different between olanzapine/samidorphan and olanzapine groups. A lower percentage of males and a lower initial body mass index were associated with the greater effect of samidorphan in preventing olanzapine-induced weight gain. Current evidence is insufficient to support the use of samidorphan to prevent olanzapine-induced weight gain and olanzapine-induced cardiometabolic abnormalities. Samidorphan is well accepted by olanzapine-treated patients.

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Low versus high level of physical resemblance in simulation for the acquisition of basic surgical skill: a meta-analysis

BMJ Simulation and Technology Enhanced Learning ◽

10.1136/bmjstel-2020-000797 ◽

2021 ◽

pp. bmjstel-2020-000797

Author(s):

Fabrizio Consorti ◽

Gianmarco Panzera

Keyword(s):

Undergraduate Students ◽

Scoring System ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Surgical Skill ◽

Undergraduate Medical Students ◽

Study Selection ◽

High Level ◽

Physical Resemblance

BackgroundMany studies explored the use of simulation in basic surgical education, with a variety of devices, contexts and outcomes, with sometimes contradictory results.ObjectivesThe objectives of this meta-analysis were to focus the effect that the level of physical resemblance in a simulation has on the development of basic surgical skill in undergraduate medical students and to provide a foundation for the design and implementation of a simulation, with respect to its effectiveness and alignment with the learning outcomes.Study selectionWe searched PubMed and Scopus database for comparative randomised studies between simulations with a different level of resemblance. The result was synthesised as the standardised mean difference, under a random effect model.FindingsWe selected 12 out of 2091 retrieved studies, reporting on 373 undergraduate students (mean of subjects 15.54±6.89). The outcomes were the performance of simple skills and the time to complete a task. Two studies reported a scoring system; seven studies reported time for a task; and three studies reported both. The total number of measures included in the meta-analysis was 456 for score and 504 for time. The pooled effect size did not show any significant advantage in a simulation of a high level of physical resemblance over a lower level, both for the scoring system (−0.19, 95% CI −0.44 to 0.06) and for time (−0.14, 95% CI −0.54 to 0.27).ConclusionSimulations with a low level of physical resemblance showed the same effect as the simulation using a higher level of resemblance on the development of basic surgical skills in undergraduate students.

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Alteration of Postural Balance in Patients with Fibromyalgia Syndrome—A Systematic Review and Meta-Analysis

Diagnostics ◽

10.3390/diagnostics11010127 ◽

2021 ◽

Vol 11 (1) ◽

pp. 127

Author(s):

David Núñez-Fuentes ◽

Esteban Obrero-Gaitán ◽

Noelia Zagalaz-Anula ◽

Alfonso Javier Ibáñez-Vera ◽

Alexander Achalandabaso-Ochoa ◽

...

Keyword(s):

Systematic Review ◽

Postural Balance ◽

Fibromyalgia Syndrome ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Healthy Controls ◽

Functional Balance ◽

Sensory Organization ◽

Effect Model

Balance problems are one of the most frequent symptoms in patients with Fibromyalgia Syndrome (FMS). However, the extent and nature of this balance disorder are not known. The objective of this work was to determine the best evidence for the alteration of postural balance in patients with FMS and analyze differences with healthy controls. To meet this objective, a systematic review with meta-analysis was performed. A bibliographical search was carried out in PubMed Medline, Scopus, Web of Science, CINAHL and SciELO. Observational studies that assessed postural balance in patients with FMS compared to healthy subjects in baseline conditions, were selected. In a random-effect model, the pooled effect was calculated with the Standardized Mean Difference (SMD) and its 95% confidence interval (CI). Nineteen studies reporting data of 2347 participants (95% female) were included. FMS patients showed poor balance with a large effect on static (SMD = 1.578; 95% CI = 1.164, 1.992), dynamic (SMD = 0.946; 95% CI = 0.598, 1.294), functional balance (SMD = 1.138; 95% CI = 0.689, 1.588) and on balance confidence (SMD = 1.194; 95% CI = 0.914, 1.473). Analysis of the Sensory Organization Test showed large alteration of vestibular (SMD = 1.631; 95% CI = 0.467, 2.795) and visual scores (SMD = 1.317; 95% CI = 0.153, 2.481) compared to healthy controls. Patients with FMS showed worse scores for different measures of postural balance compared to healthy controls. Concretely, FMS patients appear to have poor vestibular and visual scores with a possible somatosensory dependence.

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The Prevalence of Mild Cognitive Impairment among Chinese People: A Meta-Analysis

Neuroepidemiology ◽

10.1159/000512597 ◽

2021 ◽

Vol 55 (2) ◽

pp. 79-91

Author(s):

Yan Deng ◽

Siqi Zhao ◽

Guangwen Cheng ◽

Jiajia Yang ◽

Benchao Li ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diagnostic Criteria ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Internal Validity ◽

Screening Tools ◽

Chinese Elderly ◽

Pooled Prevalence

Background: Mild cognitive impairment (MCI) induced the majority number of dementia patients. The prevalence of MCI in China varied across studies with different screening tools and diagnostic criteria. Objective: A systematic review and meta-analysis was conducted to estimate the pooled MCI prevalence among the population aged 55 years and older in China. Methods: PubMed, EMBASE, CNKI, Wanfang, CQVIP, and CBMdisc were searched for studies on prevalence of MCI among Chinese elderly between January 1, 1980, and February 10, 2020. The quality assessment was conducted via external validity, internal validity, and informativity, the pooled prevalence was calculated through the random-effect model, and the homogeneity was evaluated by Cochran’s Q test and I2. Results: Fifty-three studies with 123,766 subjects were included. The pooled prevalence of MCI among Chinese elderly was 15.4% (95% CI: 13.5–17.4%). Subgroup analyses indicated that the prevalence calculated with different screening tools was 20.2% (95% CI: 15.1–25.9%) for Montreal Cognitive Assessment (MoCA) and 13.0% (95% CI: 10.7–15.5%) for Mini-Mental State Examination (MMSE). According to different diagnostic criteria, the prevalence was 14.8% (95% CI: 12.2–17.6%) for Petersen criteria, 15.0% (95% CI: 12.7–17.5%) for DSM-IV, and 21.2% (95% CI: 17.5–25.2%) for Chinese Expert Consensus on Cognitive Impairment (CECCI). Besides, women, older adults, illiterate people, rural residents, and those who lived with unhealthy lifestyles and morbidity showed higher prevalence. Conclusions: The prevalence of MCI in China was 15.4%, which varied by demographics, lifestyles, morbidity, screening tools, and diagnostic criteria. In further studies, screening tools and diagnosis criteria should be considered when estimating MCI prevalence.

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Magnitude and determinants of neural tube defect in Africa: a systematic review and meta-analysis

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-03848-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Daniel Atlaw ◽

Yohannes Tekalegn ◽

Biniyam Sahiledengle ◽

Kenbon Seyoum ◽

Damtew Solomon ◽

...

Keyword(s):

Systematic Review ◽

Neural Tube ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Folic Acid Supplementation ◽

Maternal Exposure ◽

X Ray ◽

Effect Model ◽

Pooled Prevalence

Abstract Background Neural tube defects (NTDs) are a group of disorders that arise from the failure of the neural tube close between 21 and 28 days after conception. About 90% of neural tube defects and 95% of death due to these defects occurs in low-income countries. Since these NTDs cause considerable morbidity and mortality, this study aimed to determine the prevalence and associated factors of NTDs in Africa. Methods The protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO number: CRD42020149356). All major databases such as PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, African Journals Online (AJOL), and Google Scholar search engine were systematically searched. A random-effect model was used to estimate the pooled prevalence of NTDs in Africa, and Cochran’s Q-statistics and I2 tests were used to assess heterogeneity between included studies. Publication bias was assessed using Begg ’s tests, and the association between determinant factors and NTDs was estimated using a random-effect model. Results Of the total 2679 articles, 37 articles fulfilled the inclusion criteria and were included in this systematic review and meta-analysis. The pooled prevalence of NTDs in Africa was 50.71 per 10,000 births (95% CI: 48.03, 53.44). Folic acid supplementation (AOR: 0.40; 95% CI: 0.19–0.85), maternal exposure to pesticide (AOR: 3.29; 95% CI: 1.04–10.39), mothers with a previous history of stillbirth (AOR: 3.35, 95% CI: 1.99–5.65) and maternal exposure to x-ray radiation (AOR 2.34; 95% CI: 1.27–4.31) were found to be determinants of NTDs. Conclusions The pooled prevalence of NTDs in Africa was found to be high. Maternal exposure to pesticides and x-ray radiation were significantly associated with NTDs. Folic acid supplementation before and within the first month of pregnancy was found to be a protective factor for NTDs.

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Efficacy of interventions to increase physical activity for people with heart failure: a meta-analysis

Open Heart ◽

10.1136/openhrt-2021-001687 ◽

2021 ◽

Vol 8 (1) ◽

pp. e001687

Author(s):

Aliya Amirova ◽

Theodora Fteropoulli ◽

Paul Williams ◽

Mark Haddad

Keyword(s):

Physical Activity ◽

Heart Failure ◽

Meta Analysis ◽

Behavioural Change ◽

Mode Of Delivery ◽

Random Effect ◽

Random Effect Model ◽

Action Planning ◽

Exercise Programme ◽

Effect Model

ObjectivesThis meta-analysis aims to (1) evaluate the efficacy of physical activity interventions in heart failure and (2) to identify intervention characteristics significantly associated with the interventions’ efficacy.MethodsRandomised controlled trials reporting intervention effects on physical activity in heart failure were combined in a meta-analysis using a random-effect model. Exploratory meta-analysis was performed by specifying the general approach (eg, cardiac rehabilitation), strategies used (eg, action planning), setting (eg, centre based), mode of delivery (eg, face to face or online), facilitator (eg, nurse), contact time and behavioural change theory use as predictors in the random-effect model.ResultsInterventions (n=21) had a significant overall effect (SMD=0.54, 95% CI (0.13 to 0.95), p<0.0005). Combining an exercise programme with behavioural change intervention was found efficacious (SMD=1.26, 95% CI (0.26 to 2.26), p<0.05). Centre-based (SMD=0.98, 95% CI (0.35 to 1.62), and group-based (SMD=0.89, 95% CI (0.29 to 1.50),) delivery by a physiotherapist (SMD=0.84, 95% CI (0.03 to 1.65),) were significantly associated with efficacy. The following strategies were identified efficacious: prompts/cues (SMD=3.29, 95% CI (1.97 to 4.62)), credible source (standardised mean difference, SMD=2.08, 95% CI (0.95;3.22)), adding objects to the environment (SMD=1.47, 95% CI (0.41 to 2.53)), generalisation of the target behaviour SMD=1.32, 95% CI (0.22 to 2.41)), monitoring of behaviour by others without feedback (SMD=1.02, 95% CI (0.05 to 1.98)), self-monitoring of outcome(s) of behaviour (SMD=0.79, 95% CI (0.06 to 1.52), graded tasks (SMD=0.73, 95% CI (0.22 to 1.24)), behavioural practice/rehearsal (SMD=0.72, 95% CI (0.26 to 1.18)), action planning (SMD=0.62, 95% CI (0.03 to 1.21)) and goal setting (behaviour) (SMD=0.56, 95% CI (0.03 to 1.08)).ConclusionThe meta-analysis suggests intervention characteristics that may be suitable for promoting physical activity in heart failure. There is moderate evidence in support of an exercise programme combined with a behavioural change intervention delivered by a physiotherapist in a group-based and centre-based settings.PROSPERO registerationCRD42015015280.

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