***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: Objective : To evaluate the feasibility , safety , and tolerability of noninvasive vagus nerve stimulation ( nVNS ) for the prevention of  chronic migraine ( CM ) attacks . Methods : In this first prospect i ve , multicenter , double-blind , sham-controlled pilot study of nVNS in CM prophylaxis , adults with CM ( ≥15 headache d/mo ) entered the baseline phase ( 1 month ) and were subsequently r and omized to nVNS or sham treatment  ( 2 months ) before receiving open-label nVNS treatment ( 6 months ) . The primary endpoints were safety and tolerability . Efficacy endpoints in the intent-to-treat population included change in the number of headache days per 28 days and acute medication use . Results : Fifty-nine participants ( mean age , 39.2 years ; mean headache frequency , 21.5 d/mo ) were enrolled . During the r and omized phase , tolerability was similar for nVNS ( n = 30 ) and sham treatment ( n = 29 ) . Most adverse events were mild/moderate and transient . Mean changes in the number of headache days were −1.4 ( nVNS ) and −0.2 ( sham ) ( Δ = 1.2 ; p = 0.56 ) . Twenty-seven participants completed the open-label phase . For the 15 completers initially assigned to nVNS , the mean change from baseline in headache days after 8 months of treatment was −7.9 ( 95 % confidence interval −11.9 to −3.8 ; p < 0.01 ) . Conclusions : Therapy with nVNS was well-tolerated with no safety issues . Persistent prophylactic use may reduce the number of headache days in CM ; larger sham-controlled studies are needed . Clinical Trials.gov identifier : NCT01667250 . Classification of evidence : This study provides Class II evidence that for patients with CM  , nVNS  is safe , is well-tolerated , and did not significantly change the number of headache days . This pilot study lacked the precision to exclude important safety issues or benefits of nVNS Objective To evaluate the efficacy and tolerability of single pulse transcranial magnetic stimulation ( sTMS ) for the preventive treatment of migraine . Background sTMS was originally developed for the acute treatment of migraine with aura . Open label experience has suggested a preventive benefit . The objective of this trial was to evaluate the efficacy and tolerability of sTMS for migraine prevention . Methods The e Neura S pringTMS P ost-Market O bservational U .S. S tudy of Migrain e ( ESPOUSE ) Study was a multicenter , prospect i ve , open label , observational study . From December 2014 to March 2016 , patients with migraine ( n = 263 ) were consented to complete a 1-month baseline headache diary followed by 3 months of treatment . The treatment protocol consisted of preventive ( four pulses twice daily ) and acute ( three pulses repeated up to three times for each attack ) treatment . Patients reported daily headache status , medication use , and device use with a monthly headache diary . The primary endpoint , mean reduction of headache days compared to baseline , was measured over the 28-day period during weeks 9 to 12 . The primary endpoint was compared to a statistically-derived placebo estimate ( performance goal ) . Secondary endpoints included : 50 % responder rate , acute headache medication consumption , HIT-6 , and mean reduction in total headache days from baseline of any intensity . Results Of a total of 263 consented subjects , 229 completed a baseline diary , and 220 were found to be eligible based on the number of headache days . The device was assigned to 217 subjects ( Safety Data Set ) and 132 were included in the intention to treat Full Analysis Set . For the primary endpoint , there was a −2.75 ± 0.40 mean reduction of headache days from baseline ( 9.06 days ) compared to the performance goal ( −0.63 days ) ( p < 0.0001 ) . The 50 % responder rate of 46 % ( 95 % CI 37 % , 56 % ) was also significantly higher ( p < 0.0001 ) than the performance goal ( 20 % ) . There was a reduction of −2.93 ( 5.24 ) days of acute medication use , headache impact measured by HIT-6 , −3.1 ( 6.4 ) ( p < 0.0001 ) , and total headache days of any intensity −3.16 days ( 5.21 ) compared to the performance goal ( −0.63 days ) ( p < 0.0001 ) . The most common adverse events were lightheadedness ( 3.7 % ) , tingling ( 3.2 % ) , and tinnitus ( 3.2 % ) . There were no serious adverse events . Conclusions This open label study suggests that sTMS may be an effective , well-tolerated treatment option for migraine prevention . Trial registration number Background Clinical observations and results from recent studies support the use of non-invasive vagus nerve stimulation ( nVNS ) for treating  cluster headache ( CH ) attacks .  This study compared nVNS with a sham device for acute treatment in patients with episodic or chronic CH ( eCH , cCH ) . Methods After completing a 1-week run-in period , subjects were r and omly assigned ( 1:1 ) to receive nVNS or sham therapy during a 2-week double-blind period . The primary efficacy endpoint was the proportion of all treated attacks that achieved pain-free status within 15 minutes after treatment initiation , without rescue treatment . Results The Full Analysis Set comprised 48 nVNS-treated ( 14 eCH , 34 cCH ) and 44 sham-treated ( 13 eCH , 31 cCH ) subjects . For the primary endpoint , nVNS ( 14 % ) and sham ( 12 % ) treatments were not significantly different for the total cohort . In the eCH subgroup , nVNS ( 48 % ) was superior to sham ( 6 % ; p < 0.01 ) . No significant differences between nVNS ( 5 % ) and sham ( 13 % ) were seen in the cCH subgroup . Conclusions Combing both eCH and cCH patients , nVNS was no different to sham . For the treatment of CH attacks , nVNS was superior to sham therapy in eCH but not in cCH . These results confirm and extend previous findings regarding the efficacy , safety , and tolerability of  nVNS  for the acute treatment of eCH Objective To evaluate non‐invasive vagus nerve stimulation ( nVNS ) as an acute cluster headache ( CH ) treatment . Background Many patients with CH experience excruciating attacks at a frequency that is not sufficiently addressed by current symptomatic treatments . Methods One hundred fifty subjects were enrolled and r and omized ( 1:1 ) to receive  nVNS or sham treatment  for ≤1 month during a double‐blind phase ; completers could enter a 3‐month nVNS open‐label phase . The primary end point was response rate , defined as the proportion of subjects who achieved pain relief ( pain intensity of 0 or 1 ) at 15 minutes after treatment initiation for the first CH attack without rescue medication use through 60 minutes . Secondary end points included the sustained response rate ( 15‐60 minutes ) . Subanalyses of episodic cluster headache ( eCH ) and chronic cluster headache ( cCH ) cohorts were prespecified . Results The intent‐to‐treat population comprised 133 subjects : 60 nVNS‐treated ( eCH , n = 38 ; cCH , n = 22 ) and 73 sham‐treated ( eCH , n = 47 ; cCH , n = 26 ) . A response was achieved in 26.7 % of nVNS‐treated subjects and 15.1 % of sham‐treated subjects ( P = .1 ) . Response rates were significantly higher with nVNS than with sham for the eCH cohort ( nVNS , 34.2 % ; sham , 10.6 % ; P = .008 ) but not the cCH cohort ( nVNS , 13.6 % ; sham , 23.1 % ; P = .48 ) . Sustained response rates were significantly higher with nVNS for the eCH cohort ( P = .008 ) and total population ( P = .04 ) . Adverse device effects ( ADEs ) were reported by 35/150 ( nVNS , 11 ; sham , 24 ) subjects in the double‐blind phase and 18/128 subjects in the open‐label phase . No serious ADEs occurred . Conclusions In one of the largest r and omized sham‐controlled studies for acute CH treatment , the response rate was not significantly different ( vs sham ) for the total population ; nVNS provided significant , clinical ly meaningful , rapid , and sustained benefits for eCH but not for cCH , which affected results in the total population . This safe and well‐tolerated treatment represents a novel and promising option for eCH . Clinical Trials.gov identifier : NCT01792817 BACKGROUND Preliminary work suggests that single-pulse transcranial magnetic stimulation ( sTMS ) could be effective as a treatment for migraine . We aim ed to assess the efficacy and safety of a new portable sTMS device for acute treatment of migraine with aura . METHODS We undertook a r and omised , double-blind , parallel-group , two-phase , sham-controlled study at 18 centres in the USA . 267 adults aged 18 - 68 years were enrolled into phase one . All individuals had to meet international criteria for migraine with aura , with visual aura preceding at least 30 % of migraines followed by moderate or severe headache in more than 90 % of those attacks . 66 patients dropped out during phase one . In phase two , 201 individuals were r and omly allocated by computer to either sham stimulation ( n=99 ) or sTMS ( n=102 ) . We instructed participants to treat up to three attacks over 3 months while experiencing aura . The primary outcome was pain-free response 2 h after the first attack , and co- primary outcomes were non-inferiority at 2 h for nausea , photophobia , and phonophobia . Analyses were modified intention to treat and per protocol . This trial is registered with Clinical Trials.gov , number NCT00449540 . FINDINGS 37 patients did not treat a migraine attack and were excluded from outcome analyses . 164 patients treated at least one attack with sTMS ( n=82 ) or sham stimulation ( n=82 ; modified intention-to-treat analysis set ) . Pain-free response rates after 2 h were significantly higher with sTMS ( 32/82 [ 39 % ] ) than with sham stimulation ( 18/82 [ 22 % ] ) , for a therapeutic gain of 17 % ( 95 % CI 3 - 31 % ; p=0.0179 ) . Sustained pain-free response rates significantly favoured sTMS at 24 h and 48 h post-treatment . Non-inferiority was shown for nausea , photophobia , and phonophobia . No device-related serious adverse events were recorded , and incidence and severity of adverse events were similar between sTMS and sham groups . INTERPRETATION Early treatment of migraine with aura by sTMS result ed in increased freedom from pain at 2 h compared with sham stimulation , and absence of pain was sustained 24 h and 48 h after treatment . sTMS could be a promising acute treatment for some patients with migraine with aura . FUNDING Neuralieve Objective To evaluate the efficacy , safety , and tolerability of noninvasive vagus nerve stimulation ( nVNS ; gammaCore ; electroCore , LLC , Basking Ridge , NJ ) for the acute treatment of migraine in a multicenter , double-blind , r and omized , sham-controlled trial . Methods A total of 248 participants with episodic migraine with/without aura were r and omized to receive nVNS or sham within 20 minutes from pain onset . Participants were to repeat treatment if pain had not improved in 15 minutes . Results nVNS ( n = 120 ) was superior to sham ( n = 123 ) for pain freedom at 30 minutes ( 12.7 % vs 4.2 % ; p = 0.012 ) and 60 minutes ( 21.0 % vs 10.0 % ; p = 0.023 ) but not at 120 minutes ( 30.4 % vs 19.7 % ; p = 0.067 ; primary endpoint ; logistic regression ) after the first treated attack . A post hoc repeated- measures test provided further insight into the therapeutic benefit of nVNS through 30 , 60 , and 120 minutes ( odds ratio 2.3 ; 95 % confidence interval 1.2 , 4.4 ; p = 0.012 ) . nVNS demonstrated benefits across other endpoints including pain relief at 120 minutes and was safe and well-tolerated . Conclusion This r and omized sham-controlled trial supports the abortive efficacy of nVNS as early as 30 minutes and up to 60 minutes after an attack . Findings also suggest effective pain relief , tolerability , and practicality of nVNS for the acute treatment of episodic migraine . Clinical Trials.gov identifier NCT02686034 . Classification of evidence This study provides Class I evidence that for patients with an episodic migraine , nVNS significantly increases the probability of having mild pain or being pain-free 2 hours poststimulation ( absolute difference 13.2 % ) Objective To assess the safety and efficacy of external trigeminal nerve stimulation for acute pain relief during mig 
    Output:
    
Non-invasive vagus nerve stimulation ( nVNS ) , single-transcranial magnetic stimulation and external trigeminal nerve stimulation ( all with regulatory clearance ) were well studied compared with the other devices , for which studies frequently lacked proper blinding , sham controls and sufficient population sizes .
nVNS studies demonstrated the most consistent adherence to available guidelines .