You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Sex and the risk of restless legs syndrome in the general population.
Abstract 1:
BACKGROUND Restless legs syndrome ( RLS ) is characterized by the desire to move the limbs associated with paresthesias of the legs , a motor restlessness , an intensification of symptoms at rest with relief by activity , and a worsening of symptoms in the evening or at night . Population -based studies are rare , and risk factors in the general population are not known . METHODS Cross-sectional survey with face-to-face interviews and physical examination among 4310 participants in the Study of Health in Pomerania in northeastern Germany . Participants were aged 20 to 79 years and were r and omly selected from population registers .  Restless legs syndrome was assessed with st and ardized , vali date d questions addressing the 4 minimal criteria for RLS as defined by the International Restless Legs Syndrome Study Group . RESULTS The overall prevalence of RLS was 10.6 % , increasing with age , and women were twice as often affected as men . While nulliparous women had prevalences similar to those among men up to age 64 years , the risk of RLS increased gradually for women with 1 child ( odds ratio , 1.98 ; 95 % confidence interval , 1.25 - 3.13 ) , 2 children ( odds ratio , 3.04 ; 95 % confidence interval , 2.11 - 4.40 ) , and 3 or more children ( odds ratio , 3.57 ; 95 % confidence interval , 2.30 - 5.55 ) . Subjects with RLS had significantly lower quality -of-life scores than those without the syndrome . CONCLUSIONS Restless legs syndrome is a common disease in the general population , affecting women more often than men . It is associated with reduced quality of life in cross-sectional analysis . Parity is a major factor in explaining the sex difference and may guide further clarification of the etiology of the disease


Title 2:
Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States.
Abstract 2:
This r and omized , double-blinded , placebo-controlled trial ( NCT00135993 ) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome ( RLS ) over a 6-month maintenance period . A total of 505 eligible participants with moderate to severe RLS ( IRLS sum score > or= 15 ) were r and omly assigned to five groups to receive either placebo or rotigotine ( 0.5 , 1 , 2 , or 3 mg/24 hr ) delivered by once-daily transdermal patch ( fixed-dose regimen ) . The two co- primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions ( CGI-1 ) score . On both primary measures , 2 and 3 mg/24 hr rotigotine was superior to placebo ( P < 0.001 ) . Adjusted treatment differences to placebo for the IRLS sum score were -4.5 ( 95 % CI : -6.9 , -2.2 ) for 2 mg/24 hr rotigotine , -5.2 ( 95 % CI : -7.5 , -2.9 ) for 3 mg/24 hr rotigotine , and for CGI item 1 -0.65 ( 95 % CI : -1.0 , -0.3 ) and -0.9 ( 95 % CI : -1.3 , -0.5 ) for the 2 and 3 mg/24 hr doses , respectively . Skin reactions ( 27 % ) and known dopaminergic side effects such as nausea ( 18.1 % ) and headache ( 11.6 % ) were mostly mild or moderate in rotigotine subjects . Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms . Treatment efficacy was maintained throughout the 6-month double-blind period


Title 3:
[Successful clonidine treatment of restless leg syndrome in chronic kidney insufficiency].
Abstract 3:
Restless legs syndrome is a common and sometimes incapacitating disorder in chronic uraemic patients . While therapeutic concepts have so far been disappointing , there have been recent reports on the favourable effect of clonidine in non-uraemic patients with symptoms of restless legs syndrome . Therefore , a double-blind study was conducted in 20 patients with chronic renal failure ( 11 conservatively treated , 9 on RDT ) and symptoms of restless legs . 10 patients were treated with 0.075 mg clonidine twice daily and 10 received placebo . The patients were investigated 3 days after starting therapy . - In the clonidine-treated group complete relief of symptoms was noted in 8 out of 10 patients , a striking alleviation in one , while in one further patient the symptoms remained unchanged . In contrast , only one of 10 patients in the placebo group had a mild alleviation of symptoms . Blood pressure did not differ significantly in the two groups . The data show that low-dose clonidine administration is a very effective approach in the treatment of the restless legs syndrome in chronic uraemic patients


Title 4:
The nature of placebo response in clinical studies of major depressive disorder.
Abstract 4:
OBJECTIVE To review factors influencing placebo response and clinical trial outcome in depression , and suggest ways to optimize trial success in mood disorders . DATA SOURCES PubMed search es were conducted by cross-referencing the terms depression , depressive with placebo , clinical trial , and clinical trials for studies published in English between 1970 and September 2013 . STUDY SELECTION Relevant abstract s were identified in PubMed , including clinical trials , quantitative studies , and qualitative research . We obtained and review ed relevant articles and utilized their information to synthesize the present review . DATA EXTRACTION Included articles were grouped in the following areas of relevance : ( 1 ) biological validity of illness , ( 2 ) baseline severity of illness , ( 3 ) chronicity of the index episode of depression , ( 4 ) age of participants , ( 5 ) medical and psychiatric comorbidity , ( 6 ) probability of receiving placebo , ( 7 ) use of prospect i ve treatment phases ( lead-in ) ( 8) dosing schedule , ( 9 ) trial duration , ( 10 ) frequency of follow-up assessment s , and ( 11 ) study outcome measure . RESULTS Several key elements emerge as critical to the ultimate success of a clinical trial , including the probability of receiving placebo , study duration , dosing schedule , visit frequency , the use of blinded lead-in phases , the use of central ized raters , illness severity and duration , and comorbid anxiety . CONCLUSIONS Our increasing underst and ing of the placebo response in clinical trials of major depressive disorder lends to a , gradually , more predictable phenomenon and , hopefully , to one that becomes lesser in magnitude and variability . Several elements have emerged that seem to play a critical role in trial success , gradually reshaping the design of clinical , translational , as well as mechanistic studies in depression


Title 5:
Placebo-associated improvements in motor function: comparison of subjective and objective sections of the UPDRS in early Parkinson's disease.
Abstract 5:
The Unified Parkinson 's Disease Rating Scale ( UPDRS ) is primarily composed of an investigator-derived objective rating of motor function and a patient-derived assessment of activities of daily living ( ADL ) . Using a stringent definition of placebo effect , we examined the frequency , temporal development , and stability of improvements during placebo treatment over 6 months in a large placebo-controlled trial of deprenyl and tocopherol in early Parkinson 's disease ( DATA TOP ) . One hundred ninety-nine subjects received placebo treatment in the r and omized , multicenter , placebo-controlled DATA TOP study . We compared the baseline UPDRS motor section scores with follow-up scores at 4 , 13 , and 26 weeks . Placebo-associated improvement was defined as an improvement over baseline score in motor UPDRS of at least 50 % or a change in at least two motor items at any one visit by two or more points . Seventeen percent of the 185 subjects who qualified for analysis met the placebo response criteria . The group prevalence of response was steady ( 7 % to 10 % ) at any one visit without a marked predominance of an early study effect . Older subjects with more motor impairment at baseline were most likely to show a placebo-associated improvement . ADL scores were low throughout the study , and ADL improvements did not identify the subjects with objective ly defined placebo-associated improvement . Prominent improvements in investigator-derived objective measures of Parkinson 's disease motor impairment occur during clinical trials , including one that was not aim ed at showing improved short-term efficacy . Although the notion of placebo effect often implies patient-based perceptions , we found subjective changes to be infrequent in placebo-treated patients , suggesting that either : ( 1 ) the placebo effect was rater-driven ; ( 2 ) the ADL question naire is insensitive to transient but objective ly demonstrable motor changes ; or ( 3 ) that the objective changes , albeit major , are within the realm of natural variation in the UPDRS motor scale from visit to visit


Title 6:
Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial
Abstract 6:
BACKGROUND Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome . Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome . METHODS In this r and omised , double-blind , placebo-controlled trial , 458 patients with moderate-to-severe idiopathic restless legs syndrome ( average baseline International Restless Legs Syndrome Study Group severity rating scale [ IRLS ] sum score of 28.1 ) were r and omly assigned to receive transdermal rotigotine 1 mg over 24 h ( n=115 ) , 2 mg over 24 h ( n=112 ) , or 3 mg over 24 h ( n=114 ) , or to receive placebo ( n=117 ) . Study medication was delivered via patches , applied once a day for 6 months . R and omisation was done with a computer-generated r and omisation list , stratified by centre . Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions ( CGI ) item 1 score , assessed by analysis of covariance in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00136045 . FINDINGS Efficacy analyses were done on 112 patients in the 1 mg group , 109 in the 2 mg group , 112 in the 3 mg group , and 114 in the placebo group . Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 ( SE 0.9 ) in the 1 mg group , -16.2 ( 0.9 ) in the 2 mg group , -16.8 ( 0.9 ) in the 3 mg group , and -8.6 ( 0.9 ) in the placebo group ( p<0.0001 for treatment difference vs placebo with each dose ) . Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 ( 0.14 ) in the 1 mg group , -2.41 ( 0.14 ) in the 2 mg group , -2.55 ( 0.14 ) in the 3 mg group , and -1.34 ( 0.14 ) in the placebo group ( p<0.0001 for treatment difference vs placebo with each dose ) . Skin reactions , mostly mild or moderate , were seen in 145 ( 43 % ) of 341 patients who received rotigotine and in two ( 2 % ) of 117 who received placebo .  Ten patients had serious adverse event that were deemed to be related to rotigotine :  elevation of liver enzymes ( one patient ) , worsening of tinnitus ( one patient ) , non-response to anticoagulation ( one patient ) , electrocardiogram changes ( one patient ) , and application-site reactions ( six patients ) . No admissions to hospital were needed for the application-site reactions , and they all resolved within a short time of patch removal without any other therapeutic intervention . The rate of typical dopaminergic side-effects in patients who received rotigotine was low ; no signs of augmentation were noted . INTERPRETATION 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome . FUNDING Schwarz Biosciences


Title 7:
[Treatment of idiopathic and uremic restless legs syndrome with L-dopa--a double-blind cross-over study].
Abstract 7:
In a r and omized , controlled and double-blind cross-over trial with L-Dopa and placebo we evaluated the effects of a single bedtime dose of L-Dopa 100 to 200 mg on sleep quality and frequency of periodic leg movements ( PLM ) in 17 patients with idiopathic and in 11 patients with uremic restless legs syndrome ( RLS ) by polysomnography , actigraphy , and subjective ratings . Treatment with L-Dopa showed significant reduction of the number of periodic leg movements and the PLM-index most pronounced during the first 4 hours of bedtime . Subjective evaluation confirmed improvement of sleep quality .  L-Dopa proved to be effective in idiopathic and uremic RLS without any severe side effects
The placebo and nocebo responses were greater in trials with longer duration , evaluating pharmacologic interventions and idiopathic RLS , and in industry-funded and unpublished studies .
The placebo response was considerably smaller in objective as compared to subjective outcomes .
In addition , the nocebo response increases proportionally with the placebo response , and has the same predictors .
Conclusions : The magnitude of the placebo response in RLS is above the threshold of minimal clinical important difference , and the frequency of adverse events is also considerable .