***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES The objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF . BACKGROUND Increased sympathetic and decreased parasympathetic activity contribute to heart failure ( HF ) symptoms and disease progression . Baroreflex activation therapy ( BAT ) results in central ly mediated reduction of sympathetic outflow and increased parasympathetic activity . METHODS Patients with New York Heart Association ( NYHA ) functional class III HF and ejection fractions ≤35 % on chronic stable guideline -directed medical therapy ( GDMT ) were enrolled at 45 centers in the United States , Canada , and Europe . They were r and omly assigned to receive ongoing GDMT alone ( control group ) or ongoing GDMT plus BAT ( treatment group ) for 6 months . The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events . The primary efficacy end points were changes in NYHA functional class , quality -of-life score , and 6-minute hall walk distance . RESULTS One hundred forty-six patients were r and omized , 70 to control and 76 to treatment . The major adverse neurological and cardiovascular event-free rate was 97.2 % ( lower 95 % confidence bound 91.4 % ) . Patients assigned to BAT , compared with control group patients , experienced improvements in the distance walked in 6 min ( 59.6 ± 14 m vs. 1.5 ± 13.2 m ; p = 0.004 ) , quality -of-life score ( -17.4 ± 2.8 points vs. 2.1 ± 3.1 points ; p < 0.001 ) , and NYHA functional class ranking ( p = 0.002 for change in distribution ) . BAT  significantly reduced N-terminal pro-brain natriuretic peptide ( p = 0.02 ) and was associated with a trend toward fewer days hospitalized for HF ( p = 0.08 ) . CONCLUSIONS BAT  is safe and improves functional status , quality of life , exercise capacity , N-terminal pro-brain natriuretic peptide , and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF . ( Barostim Neo System in the Treatment of Heart Failure ; NCT01471860 ; Barostim HOPE4HF [ Hope for Heart Failure ] Study ; NCT01720160 ) BACKGROUND Previous trials have demonstrated clinical ly significant and durable reductions in arterial pressure from baroreflex activation therapy ( BAT ) , result ing from electrical stimulation of the carotid sinus using a novel implantable device . A second-generation system for delivering BAT , the Barostim neo ™ system , has been design ed to deliver BAT with a simpler device and implant procedure . METHODS BAT , delivered with the advanced system , was evaluated in a single-arm , open-label study of patients with resistant hypertension , defined as resting systolic blood pressure ( SBP ) ≥140 mm Hg despite treatment with ≥3 medications , including ≥1 diuretic . Stable medical therapy was required for ≥4 weeks before establishing pretreatment baseline by averaging two SBP readings taken ≥24 hours apart . RESULTS Thirty patients enrolled from seven centers in Europe and Canada . From a baseline of 171.7 ± 20.2/99.5 ± 13.9 mm Hg , arterial pressure decreased by 26.0 ± 4.4/12.4 ± 2.5 mm Hg at 6 months . In a subset ( n = 6 ) of patients with prior renal nerve ablation  , arterial pressure decreased by 22.3 ± 9.8 mm Hg . Background medical therapy for hypertension was unchanged during follow-up . Three minor procedure-related complications occurred within 30 days of implant . All complications resolved without sequelae . CONCLUSION BAT delivered with the second-generation system significantly lowers blood pressure in resistant hypertension with stable , intensive background medical therapy , consistent with studies of the first-generation system for electrical activation of the baroreflex , and provides a safety profile comparable to a pacemaker The purpose of this publication is to describe the intraoperative experience along with long-term safety and efficacy of the second-generation baroreflex activation therapy ( BAT ) system in patients with heart failure ( HF ) and reduced ejection fraction HF ( HFrEF ) . In a r and omized trial of New York Heart Association Class III HFrEF , 140 patients were assigned 1:1 to receive BAT plus medical therapy or medical therapy alone . Procedural information along with safety and efficacy data were collected and analyzed over 12 months . Within the cohort of 71 patients r and omized to BAT  , implant procedure time decreased with experience , from 106 ± 37 minutes on the first case to 83 ± 32 minutes on the third case . The rate of freedom from system- and procedure-related complications was 86 % through 12 months , with the percentage of days alive without a complication related to system , procedure , or underlying cardiovascular condition identical to the control group . The complications that did occur were generally mild and short-lived . Overall , 12 months therapeutic benefit from BAT was consistent with previously reported efficacy through 6 months : there was a significant and sustained beneficial treatment effect on New York Heart Association functional Class , quality of life , 6-minute hall walk distance , plasma N-terminal pro-brain natriuretic peptide , and systolic blood pressure . This was true for the full trial cohort and a predefined subset not receiving cardiac resynchronization therapy . There is a rapid learning curve for the specialized procedures entailed in a BAT system implant . BAT system implantation is safe with the therapeutic benefits of BAT in patients with HFrEF being substantial and maintained for at least 1 year Aims : Baroreflex activation therapy ( BAT ) has recently been shown to reduce muscle sympathetic nerve activity and hospitalization rate while improving clinical variables through 6 months of therapy in patients with heart failure and reduced ejection fraction ( HFrEF ) . The objective of the present study is to extend the information on this patient cohort over a long-term follow-up . Methods and results : Eleven patients were enrolled in the study and presented with optimized , stable medical therapy , New York Heart Association Class III HFrEF with left ventricular ejection fraction 40 % or less , impaired functional capacity and no active cardiac resynchronization therapy . For the present report , muscle sympathetic nerve activity , baroreflex sensitivity data and hospitalization rate together with st and ard clinical data were collected at 12 and 21.5 ± 4.2 months following BAT activation . Two patients died during long-term follow-up . The remaining nine patients maintained the improvements observed at 6 months , including reduced sympathetic activity and rates of hospitalization . Conclusion : BAT provides long-term chronic reductions in sympathetic activity and utilization of hospital re sources in patients with HFrEF . General clinical presentation , quality of life and functional capacity are likewise improved and maintained . The temporal association of BAT with sympathetic drive diminution and improvement in objective clinical measures suggests a cause- and -effect relationship that will be verified in future r and omized controlled trials of outcome Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND In a r and omized trial , baroreflex activation therapy ( BAT ) improved exercise capacity , quality of life and NT-proBNP in patients with heart failure with reduced ejection fraction ( HFrEF ) . In view of different mechanisms underlying HFrEF , we performed a post-hoc subgroup analysis of efficacy and safety of BAT in patients with and without coronary artery disease ( CAD ) . METHODS AND RESULTS Patients with left ventricular ejection fraction < 35 % and NYHA Class III were r and omized 1:1 to guideline -directed medical and device therapy alone or plus BAT .  Patients with a history of CAD , prior myocardial infa rct ion or coronary artery bypass graft were assigned to the CAD group with all others assigned to the no-CAD group . Of 71 BAT treated patients , 52 had CAD and 19 had no CAD . In the control group , 49 of 69 patients had CAD and 20 had no CAD . The system- or procedure-related major adverse neurological or cardiovascular event rate was 3.8 % in the CAD group vs. 0 % in the no-CAD group ( p = 1.0 ) . In the whole cohort , NYHA Class , Minnesota Living with Heart Failure score , 6-minute hall walk distance and NTproBNP were improved in BAT treated patients compared with controls . Statistical analyses revealed no interaction between the presence of CAD and effect of BAT ( all p > 0.05 ) . CONCLUSION No major differences were found in  BAT efficacy or safety between patients with and without CAD , indicating that BAT improves exercise capacity , quality of life and NTproBNP in patients with ischemic and non-ischemic cardiomyopathy . CLINICAL TRIALS . GOV IDENTIFIER NCT01471860 and NCT01720160 Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation  to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies AIMS Increased sympathetic and decreased parasympathetic activity contribute to heart failure ( HF ) symptoms and disease progression . Carotid baroreceptor stimulation ( baroreflex activation therapy , BAT ) results in central ly mediated reduction of sympathetic and increase in parasympathetic activity . Because patients treated with cardiac resynchronization therapy ( CRT )  may have less sympathetic/parasympathetic imbalance , we hypothesized that there would be differences in the response to BAT in patients with CRT vs. those without CRT . METHODS AND RESULTS New York Heart Association ( NYHA ) Class III patients with an ejection fraction ( EF ) ≤35 % were r and omized ( 1 : 1 ) to ongoing guideline -directed medical and device therapy ( GDMT , control ) or ongoing GDMT plus BAT .  Safety endpoint was system-/procedure-related major adverse neurological and cardiovascular events ( MANCE ) . Efficacy endpoints were Minnesota Living with Heart Failure Quality of Life ( QoL ) , 6-min hall walk distance ( 6MHWD ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , left ventricular ejection fraction ( LVEF ) , and HF hospitalization rate . In this sample , 146 patients were r and omized ( 70 control ; 76 BAT ) and were 140 activated ( 45 with CRT and 95 without CRT ) . MANCE-free rate at 6 months was 100 % in CRT and 96 % in no-CRT group . At 6 months , in the no-CRT group , QoL score , 6MHWD , LVEF , NT-proBNP and HF hospitalizations were significantly improved in BAT patients compared with controls . Changes in efficacy endpoints in the CRT group favoured BAT ; however , the improvements were less than in the no-CRT group and were not statistically different from control . CONCLUSIONS BAT is safe and significantly improved QoL , exercise capacity , NTpro-BNP , EF , and rate of HF hospitalizations in GDMT-treated NYHA Class III HF patients . These effects were most pronounced in patients not treated with CRT 
    Output:
    
The procedure seems to be safe when performed by a well‐trained multi‐professional team .
Improvements in New York Heart Association class of heart failure , quality of life , 6 min walk test , and hospitalization rates , as well as in muscle sympathetic nerve activity .
BAT procedure seems to be safe if appropriate training is provided .
Improvements in clinical outcomes were described in all included studies .