***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  Variability  in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , UK ) in patients with severe chronic venous insufficiency . Patients with severe venous hypertension ( chronic venous insufficiency , ankle swelling ) and history of venous ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily ) for 8 weeks . A group of 21 patients was included in the treatment group and 18 equivalent patients were observed as controls ( no treatment during the observation period ) . All 21 patients ( age 53 years ; range , 42 - 60 years ; M : F=11:10 ) in the treatment group completed the 8-week study . Also the 18 controls completed the follow-up period . There were no drop-outs . The average ambulatory venous pressure was 59.3 ( SD 7.2 ; range 50 - 68 ) with a refilling time shorter than 10 seconds ( average 7.6 ; SD 3 ) . There were no differences in ambulatory venous pressure or refilling time between the treatment and control patients . The duration of the disease — from the first signs/symptoms — was on average 5.7 years ( SD 2.1 ) . At 4 and 8 weeks , in all Pycnogenol-treated subjects , microcirculatory and clinical evaluations indicated a progressive decrease in skin flux , indicating an improvement in the level of microangiopathy ; a significant decrease in capillary filtration ; a significant improvement in the symptomatic score ; and a reduction in edema . There were no visible effects in controls . In conclusion , this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy . The study indicates the significant clinical role of Pycnogenol in the management , treatment and control of this common clinical problem . The treatment may be also useful to prevent ulcerations by controlling the level of venous microangiopathy The purpose of this r and omized , double-blind and placebo controlled study was to test the effect of polyphenolic extract of pine bark Pycnogenol ® ( Pyc ) on the level of oxidized purines represented by 8-oxo-7,8-dihydroguanine ( 8-oxoG ) and on the total antioxidant status ( TAS ) in children with attention deficit/hyperactivity disorder ( ADHD ) . We have found significantly increased damage to DNA in ADHD children when compared to controls . 8-oxoG was significantly lower after 1 month of Pyc administration in comparison to the beginning state and to placebo  group . TAS in ADHD children was lower in comparison to controls . After Pyc  administration , TAS was elevated but statistically significant increase was recorded after 1 month of termination of Pyc application . Improvement of DNA damage and TAS after Pyc administration is associated with the improvement of attention in ADHD children . In conclusion , Pycnogenol ® administration reduces oxidative damage to DNA , normalizes TAS and improves attention of ADHD children . Explanation of mutual relation between oxidative damage to DNA , TAS and symptoms of ADHD and mechanism of Pyc 's action needs further investigations Melasma ( or chloasma ) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women . The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects . Pycnogenol is a st and ardized extract of the bark of the French maritime pine ( Pinus pinaster ) , a well-known , potent antioxidant . Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition , it recycles vitamin C , regenerates vitamin E and increases the endogenous antioxidant enzyme system . Pycnogenol protects against ultraviolet ( UV ) radiation . Therefore its efficacy in the treatment of melasma was investigated . Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily , i.e. 75 mg Pycnogenol per day . These patients were evaluated clinical ly by parameters such as the melasma area index , pigmentary intensity index and by routine blood and urine tests . After a 30-day treatment , the average melasma area of the patients decreased by 25.86 + /- 20.39 mm(2 ) ( p < 0.001 ) and the average pigmentary intensity decreased by 0.47 + /- 0.51 unit ( p < 0.001 ) . The general effective rate was 80 % . No side effect was observed . The results of the blood and urine test parameters at baseline and at day 30 were within the normal range . Moreover , several other associated symptoms such as fatigue , constipation , pains in the body and anxiety were also improved . To conclude , Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy The aim of this study was to compare the efficacy of Venostasin ( horse chestnut seed extract ) and Pycnogenol ( French maritime pine bark extract ) in the treatment of chronic venous insufficiency ( CVI ) . In an open , controlled comparative study 40 patients with diagnosed CVI were treated either with 600 mg chestnut seed extract per day or 360 mg Pycnogenol per day over a period of 4 weeks . The following parameters were investigated before the start of treatment and after 2 and 4 weeks of treatment : circumference of the lower legs and rating of subjective symptoms ( scores ) of pain , cramps , night-time swelling , feeling of " heaviness " , and reddening of the skin . In addition , blood levels of cholesterol LDL and HDL were determined before and at the end of treatment . Pycnogenol significantly reduced the circumference of the lower limbs and significantly improved subjective symptoms . Furthermore , Pycnogenol significantly decreased cholesterol and LDL values in the blood , whereas HDL remained unaffected . Venostasin only moderately but not significantly , reduced the circumference of the lower limbs and marginally improved symptoms .  Venostasin had no influence on the determined lipid values . Both medications were equally well tolerated . In conclusion , Pycnogenol was found to be more efficacious than Venostasin for the treatment of CVI The aim of this study was to investigate the clinical efficacy of oral Pycnogenol ® ( Horphag Research Ltd , United Kingdom ) in patients with diabetic microangiopathy . Patients without a history of diabetic ulcerations were treated with Pycnogenol . Patients received oral Pycnogenol ( 50 mg capsules , 3 times daily for a total of 150 mg daily for 4 weeks ) . A group of 30 patients was included ( severe microangiopathy ) ; 30 comparable patients were observed as controls ( no treatment during the observation period ) . All patients ( age , 59 years ; range , 55 - 68 years ; male : female = 18:12 ) included in the treatment group completed the 4-week study . Also , all controls completed the follow-up period . There were no drop-outs . All included subjects had signs and symptoms of diabetic microangiopathy . The duration of diabetes — from the first signs/symptoms — was on average 7.5 years ( SD = 3 ) . After 4 weeks , microcirculatory and clinical evaluations showed a progressive decrease in skin flux at rest in the foot ( indicating an improvement in the level of microangiopathy ) , a significant decrease in capillary filtration , and a significant improvement in the venoarteriolar response in all treated subjects . There were no visible effects in controls except a slight reduction in skin flux at rest in the foot . Treatment was well tolerated in both groups . In conclusion , this study confirms the clinical efficacy of Pycnogenol in patients with diabetic microangiopathy . The study indicates the clinical role of Pycnogenol in the management , treatment , and control of this common clinical problem . The treatment may be also useful to prevent diabetic ulcerations by controlling the level of microangiopathy OBJECTIVE The safe and efficacious use of Pycnogenol ( French maritime pine bark extract ) in other inflammatory diseases prompted this study of its antiinflammatory effects in patients with osteoarthritis ( OA ) . The aim of the study was to evaluate whether Pycnogenol reduces the symptoms of OA in a double-blind , placebo-controlled , r and omly allocated trial with patients suffering from knee osteoarthritis stages I and II . METHODS 100 patients were treated for 3 months either by 150 mg Pycnogenol per day at meals or by placebo . Patients had to report any change of use of previously prescribed antiinflammatory medication during the study period . Patients filled the Western Ontario and Mc Masters University ( WOMAC ) question naire for osteoarthritis every 2 weeks and evaluated weekly pain symptoms using a visual analogue scale for pain intensity . RESULTS Following treatment with Pycnogenol patients reported an improvement of WOMAC index ( p < 0.05 ) , and a significant alleviation of pain by visual analogue scale ( p < 0.04 ) , the placebo had no effect . The use of analgesics diminished in the verum group but increased under the placebo . Treatment with Pycnogenol was well tolerated . CONCLUSION Results show that Pycnogenol  in patients with mild to moderate OA improves symptoms and is able to spare NSAIDs Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease ( CVD ) . We investigated the clinical effectiveness of Pycnogenol , a flavonoid-rich dietary supplement , in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes . Forty-eight individuals were enrolled in a r and omized , double-blind , placebo-controlled trial with parallel-group design . Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme ( ACE ) inhibitors .  Subjects were r and omly assigned to receive either Pycnogenol pill ( 125 mg daily ) or matched placebo for 12 weeks . According to the values of blood pressure ( BP ) measured at 2-week intervals , the pretrial ACE inhibitor dosage was left unchanged , reduced by 50 % , or brought back to the pretrial dosage until a stable BP was obtained . Fasting plasma glucose , low-density lipoprote 
    Output:
    
Current evidence is insufficient to support Pycnogenol ( ® ) use for the treatment of any chronic disorder .