human
***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: Abstract — Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function . Recently , the biological clock was shown to be involved in autonomic cardiovascular regulation . Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension . We conducted a r and omized , double-blind , placebo-controlled , crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute ( single ) and repeated ( daily for 3 weeks ) oral melatonin ( 2.5 mg ) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality . Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg , respectively . The treatment did not affect heart rate . The day – night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15 % and 25 % , respectively . A single dose of melatonin had no effect on blood pressure . Repeated ( but not acute ) melatonin also improved sleep . Improvements in blood pressure and sleep were statistically unrelated . In patients with essential hypertension , repeated bedtime melatonin intake significantly reduced nocturnal blood pressure . Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake . The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus ( DM ) . The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient , and associated with oxidative stress induced by long-term hyperglycemia . The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs , e.g. metformin , which act through this pathway . This project was design ed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin .  A placebo-controlled , double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups . These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone : 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo , given at bedtime for 90 days . Fasting lipid profiles and microalbuminuria ( MAU ) were measured before initiating the treatments ( zero time ) and after 30 and 90 days of treatment . Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU ; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent . In conclusion , the combination of melatonin and zinc acetate , when used alone or in combination with metformin , improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients OBJECTIVES The aim of this study was to assess the relations between the circadian variations of blood pressure ( BP ) and the pattern of ischemia and autonomic activity in normotensive and hypertensive patients with coronary artery disease ( CAD ) . PATIENTS AND METHODS On the basis of the results of ambulatory BP monitoring , 115 patients with stable CAD were divided into Group 1 ( with arterial hypertension ) and Group 2 ( normotensives ) . Groups were subdivided into dippers and non-dippers . Holter monitoring was performed to assess the occurrence and circadian pattern of ischemic episodes . Time domain and frequency domain HRV analyses were performed to evaluate the autonomic activity . RESULTS The total number of ischemic episodes was similar in dippers and non-dippers . Non-dippers had a greater number of silent episodes and a different circadian pattern of ischemia with more night episodes . Among the time-domain HRV parameters , only SDNN was similar in dippers and non-dippers . Non-dippers had lower pNN50 and rMSSD-the parameters expressing parasympathetic activity . Differences between diurnal and nocturnal results of spectral HRV analysis were observed in dipper patients only . They presented an elevation of HF power and a decline of LF power at night . All differences between dippers and non-dippers were of similar significance in both hypertensives and normotensives . CONCLUSIONS A lack of a nocturnal fall in BP is present in normotensive and hypertensive patients with CAD . Non-dippers with CAD had silent and nighttime ischemia more often . They also had an abnormal pattern of autonomic activity with higher sympathetic and lower parasympathetic modulation PURPOSE Nocturnal hypertension is associated with a high risk of morbidity and mortality . A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients . We therefore studied the potency of melatonin to reduce nighttime blood pressure ( BP ) in treated hypertensive patients with nocturnal hypertension . PATIENTS AND METHODS Thirty-eight treated hypertensive patients ( 22 males , mean age 64+/-11 years ) with confirmed nocturnal hypertension ( mean nighttime systolic BP > 125 mm Hg ) , according to repeated 24-hour ambulatory blood pressure monitoring ( ABPM ) , were r and omized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks . A 24-hour ABPM was then performed . RESULTS Melatonin treatment reduced nocturnal systolic BP significantly from 136+/-9 to 130+/-10 mm Hg ( P=.011 ) , and diastolic BP from 72+/-11 to 69+/-9 mm Hg ( P=.002 ) , whereas placebo had no effect on nocturnal BP . The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo ( P=.01 ) , and was most prominent between 2:00 AM and 5:00 AM ( P=.002 ) . CONCLUSIONS Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension . Thus , an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension AIMS As melatonin has been found to play a role in the mechanisms of cardiovascular regulation , we design ed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy . METHODS Forty-seven mild to moderate essential hypertensive out patients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months , were given placebo or melatonin  5  mg at 22.30 h for 4 weeks according to a double-blind cross-over study . At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring  ( ABPM ) during usual working days ; sleeping period was scheduled to last from 23.00 to 07.00 h. RESULTS The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period ( DeltaSBP = + 6.5 mmHg , P < 0.001 ; DeltaDBP = + 4.9 mmHg , P < 0.01 ; DeltaHR = + 3.9 beats min-1 , P < 0.01 ) . The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours . CONCLUSIONS We hypothesize that competition between melatonin and nifedipine , is able to impair the antihypertensive efficacy of the calcium channel blocker . This suggests caution in uncontrolled use of melatonin in hypertensive patients . As the pineal hormone might interfere with calcium channel blocker therapy , it can not be considered simply a dietary supplement The aim of this study was to assess the effects of 5 mg melatonin before sleep in patients with coronary artery disease ( CAD ) and with an abnormal circadian pattern of blood pressure ( BP ) on changes in circadian BP profile and heart rate variability ( HRV ) . Sixty patients with CAD , nondippers aged 48–80 years ( male 75 % ) , were included . In addition to previous treatment , they were r and omly allocated to melatonin or placebo . After 90 days , a second 24-h BP monitoring was carried out . Each patient had two sessions ( before r and omization and at the end of study ) of 24-h ECG monitoring to assess the changes in HRV . Inclusion of melatonin led to BP pattern normalization in 35 % of patients in the melatonin group and in 15 % of controls ( P=0.609 ) . This effect was reached not only by a decrease in nighttime BP , but also by an increase in daytime BP ( significant in the melatonin group ) . A nonoptimal effect for BP profile was observed in 12.5 % of patients : extreme- or reverse dippers . In patients with conversion from nondippers to dippers ( responders ) , an increase in st and ard deviation of normal-to-normal intervals between initial and final HRV analyses was observed . Nonresponders represented an increase in the mean circadian heart rate . To avoid nonoptimal effects , the inclusion of melatonin in pharmacotherapy of patients with CAD should be based on monitoring of circadian BP profile , before and during treatment . As melatonin caused not only a nocturnal decrease in BP but also a daytime increase , it should not be recommended in patients with ‘ high normal ’ values of BP because of the danger of induction of arterial hypertension BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions  to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application In this study it was investigated whether the oral administration of melatonin ( 1 mg ) in comparison to placebo was able to reduce blood pressure , vascular reactivity , and catecholamines  in men , as previously reported in young women . The administration of melatonin significantly reduced blood pressure , the pulsatility index in the internal carotid artery , and catecholamines levels within 90 minutes . The effect of melatonin on the artery pulsatility index was related to baseline values , being greater in men with higher baseline values . The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implication AIMS The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation ( AF ) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF , among individuals with type 2 diabetes . METHODS AND RESULTS About 11 140 patients with type 2 diabetes ( 7.6 % of whom had AF at baseline ) were r and omized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . We compared total mortality and cardiovascular disease outcomes and effects of r and omized treatment for 4.3 years on such outcomes between patients with and without AF at baseline . After multiple adjustments , AF was associated with a 61 % ( 95 % confidence interval 31 - 96 , P < 0.0001 ) greater risk of all-cause mortality and comparable higher risks of cardiovascular death , stroke , and heart failure ( all P < 0.001 ) . Routine treatment with a fixed combination of perindopril and indapamide produced similar relative , but greater absolute , risk reductions for all-cause and cardiovascular mortalities in patients with AF , compared with those without AF . The number of patients needed to be treated with perindopril- 
    Output:
    
agent
In summary , the current meta- analysis demonstrated that melatonin supplementation  significantly decreased SBP and DBP in patients with metabolic disorders .
***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: Abstract — Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function . Recently , the biological clock was shown to be involved in autonomic cardiovascular regulation . Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension . We conducted a r and omized , double-blind , placebo-controlled , crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute ( single ) and repeated ( daily for 3 weeks ) oral melatonin ( 2.5 mg ) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality . Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg , respectively . The treatment did not affect heart rate . The day – night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15 % and 25 % , respectively . A single dose of melatonin had no effect on blood pressure . Repeated ( but not acute ) melatonin also improved sleep . Improvements in blood pressure and sleep were statistically unrelated . In patients with essential hypertension , repeated bedtime melatonin intake significantly reduced nocturnal blood pressure . Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake . The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus ( DM ) . The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient , and associated with oxidative stress induced by long-term hyperglycemia . The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs , e.g. metformin , which act through this pathway . This project was design ed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin .  A placebo-controlled , double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups . These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone : 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo , given at bedtime for 90 days . Fasting lipid profiles and microalbuminuria ( MAU ) were measured before initiating the treatments ( zero time ) and after 30 and 90 days of treatment . Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU ; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent . In conclusion , the combination of melatonin and zinc acetate , when used alone or in combination with metformin , improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients OBJECTIVES The aim of this study was to assess the relations between the circadian variations of blood pressure ( BP ) and the pattern of ischemia and autonomic activity in normotensive and hypertensive patients with coronary artery disease ( CAD ) . PATIENTS AND METHODS On the basis of the results of ambulatory BP monitoring , 115 patients with stable CAD were divided into Group 1 ( with arterial hypertension ) and Group 2 ( normotensives ) . Groups were subdivided into dippers and non-dippers . Holter monitoring was performed to assess the occurrence and circadian pattern of ischemic episodes . Time domain and frequency domain HRV analyses were performed to evaluate the autonomic activity . RESULTS The total number of ischemic episodes was similar in dippers and non-dippers . Non-dippers had a greater number of silent episodes and a different circadian pattern of ischemia with more night episodes . Among the time-domain HRV parameters , only SDNN was similar in dippers and non-dippers . Non-dippers had lower pNN50 and rMSSD-the parameters expressing parasympathetic activity . Differences between diurnal and nocturnal results of spectral HRV analysis were observed in dipper patients only . They presented an elevation of HF power and a decline of LF power at night . All differences between dippers and non-dippers were of similar significance in both hypertensives and normotensives . CONCLUSIONS A lack of a nocturnal fall in BP is present in normotensive and hypertensive patients with CAD . Non-dippers with CAD had silent and nighttime ischemia more often . They also had an abnormal pattern of autonomic activity with higher sympathetic and lower parasympathetic modulation PURPOSE Nocturnal hypertension is associated with a high risk of morbidity and mortality . A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients . We therefore studied the potency of melatonin to reduce nighttime blood pressure ( BP ) in treated hypertensive patients with nocturnal hypertension . PATIENTS AND METHODS Thirty-eight treated hypertensive patients ( 22 males , mean age 64+/-11 years ) with confirmed nocturnal hypertension ( mean nighttime systolic BP > 125 mm Hg ) , according to repeated 24-hour ambulatory blood pressure monitoring ( ABPM ) , were r and omized in a double-blind fashion to receive either controlled release (CR)-melatonin 2 mg or placebo 2 hours before bedtime for 4 weeks . A 24-hour ABPM was then performed . RESULTS Melatonin treatment reduced nocturnal systolic BP significantly from 136+/-9 to 130+/-10 mm Hg ( P=.011 ) , and diastolic BP from 72+/-11 to 69+/-9 mm Hg ( P=.002 ) , whereas placebo had no effect on nocturnal BP . The reduction in nocturnal systolic BP was significantly greater with melatonin than with placebo ( P=.01 ) , and was most prominent between 2:00 AM and 5:00 AM ( P=.002 ) . CONCLUSIONS Evening CR-melatonin 2 mg treatment for 4 weeks significantly reduced nocturnal systolic BP in patients with nocturnal hypertension . Thus , an addition of melatonin 2 mg at night to stable antihypertensive treatment may improve nocturnal BP control in treated patients with nocturnal hypertension AIMS As melatonin has been found to play a role in the mechanisms of cardiovascular regulation , we design ed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy . METHODS Forty-seven mild to moderate essential hypertensive out patients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months , were given placebo or melatonin  5  mg at 22.30 h for 4 weeks according to a double-blind cross-over study . At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring  ( ABPM ) during usual working days ; sleeping period was scheduled to last from 23.00 to 07.00 h. RESULTS The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period ( DeltaSBP = + 6.5 mmHg , P < 0.001 ; DeltaDBP = + 4.9 mmHg , P < 0.01 ; DeltaHR = + 3.9 beats min-1 , P < 0.01 ) . The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours . CONCLUSIONS We hypothesize that competition between melatonin and nifedipine , is able to impair the antihypertensive efficacy of the calcium channel blocker . This suggests caution in uncontrolled use of melatonin in hypertensive patients . As the pineal hormone might interfere with calcium channel blocker therapy , it can not be considered simply a dietary supplement The aim of this study was to assess the effects of 5 mg melatonin before sleep in patients with coronary artery disease ( CAD ) and with an abnormal circadian pattern of blood pressure ( BP ) on changes in circadian BP profile and heart rate variability ( HRV ) . Sixty patients with CAD , nondippers aged 48–80 years ( male 75 % ) , were included . In addition to previous treatment , they were r and omly allocated to melatonin or placebo . After 90 days , a second 24-h BP monitoring was carried out . Each patient had two sessions ( before r and omization and at the end of study ) of 24-h ECG monitoring to assess the changes in HRV . Inclusion of melatonin led to BP pattern normalization in 35 % of patients in the melatonin group and in 15 % of controls ( P=0.609 ) . This effect was reached not only by a decrease in nighttime BP , but also by an increase in daytime BP ( significant in the melatonin group ) . A nonoptimal effect for BP profile was observed in 12.5 % of patients : extreme- or reverse dippers . In patients with conversion from nondippers to dippers ( responders ) , an increase in st and ard deviation of normal-to-normal intervals between initial and final HRV analyses was observed . Nonresponders represented an increase in the mean circadian heart rate . To avoid nonoptimal effects , the inclusion of melatonin in pharmacotherapy of patients with CAD should be based on monitoring of circadian BP profile , before and during treatment . As melatonin caused not only a nocturnal decrease in BP but also a daytime increase , it should not be recommended in patients with ‘ high normal ’ values of BP because of the danger of induction of arterial hypertension BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions  to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application In this study it was investigated whether the oral administration of melatonin ( 1 mg ) in comparison to placebo was able to reduce blood pressure , vascular reactivity , and catecholamines  in men , as previously reported in young women . The administration of melatonin significantly reduced blood pressure , the pulsatility index in the internal carotid artery , and catecholamines levels within 90 minutes . The effect of melatonin on the artery pulsatility index was related to baseline values , being greater in men with higher baseline values . The present data indicate that melatonin may blunt the activity of the cardiovascular system and may have both physiopathologic and clinical implication AIMS The aim of this study was to investigate serious clinical outcomes associated with atrial fibrillation ( AF ) and the effects of routine blood pressure lowering on such outcomes in the presence or absence of AF , among individuals with type 2 diabetes . METHODS AND RESULTS About 11 140 patients with type 2 diabetes ( 7.6 % of whom had AF at baseline ) were r and omized to a fixed combination of perindopril and indapamide or placebo in the Action in Diabetes and Vascular Disease : preterAx and diamicroN-MR Controlled Evaluation ( ADVANCE ) study . We compared total mortality and cardiovascular disease outcomes and effects of r and omized treatment for 4.3 years on such outcomes between patients with and without AF at baseline . After multiple adjustments , AF was associated with a 61 % ( 95 % confidence interval 31 - 96 , P < 0.0001 ) greater risk of all-cause mortality and comparable higher risks of cardiovascular death , stroke , and heart failure ( all P < 0.001 ) . Routine treatment with a fixed combination of perindopril and indapamide produced similar relative , but greater absolute , risk reductions for all-cause and cardiovascular mortalities in patients with AF , compared with those without AF . The number of patients needed to be treated with perindopril- 
    Output:
    