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: 1 . The objective of this study was to investigate the efficacy of home-medicated non-steroidal anti-inflammatory ( NSAID ) analgesics , using an electronic patient diary . Single doses of ketoprofen 25 mg and ketoprofen 50 mg were compared with ibuprofen 200 mg and placebo in the treatment of a single occasion of episodic tension-type headache , using a double-blind , r and omized , parallel group design . 2 . A total of 166 patients with headache compatible with episodic tension-type headache and no refractory headaches or contraindications to NSAIDs  were contacted by advertisements and selected by question naires . Patients performed the study at home , using an electronic diary for headache assessment , with a form to allow comments and corrections . Visual analogue scales ( VAS 10 cm ) of headache severity , five-item headache relief rating ( HRR ) scales , and time of intake of ' escape ' analgesics were scored regularly , for 4 h following intake of trial medication . 3 . VAS-scores ( n = 1407 ) and HRRs ( n = 452 ) were returned by 159 patients . Of these scores , 1.5 % were inadvertently omitted from the electronic diary or modified on the comment forms . 4 . Headache ( VAS and HRR ) improved more with all three NSAIDs than with placebo , although the effect of ibuprofen was significant for HRR only . After 2 and 4 h respectively , the reduction in VAS-ratios was 17 and 19 % with placebo , 18 and 53 % with ibuprofen 200 mg , 41 and 61 % with ketoprofen 25 mg , and 47 and 59 % with ketoprofen 50 mg . After 4 h , headache improved strongly ( highest HRR ) in 18 % of patients on placebo , 39 % on ibuprofen 200 mg , 62 % on ketoprofen 25 mg , and 55 % on ketoprofen 50 mg . Headache disappeared completely ( VAS-score = 0 ) in one patient ( 3 % ) with placebo ( after 180 min ) , 10 % with ibuprofen 200 mg ( average 211 min ) , 18 % with ketoprofen 25 mg ( 159 min ) , and 28 % with ketoprofen 50 mg ( 146 min ) . 5 . The effects of ketoprofen 50 mg were more pronounced than those of ibuprofen 200 mg , which seemed to start later . Ketoprofen 25 mg and 50 mg were very similar , suggesting a maximal effect of the lower dose . Mild to moderate adverse events were reported by 9 % of the patients , half of which occurred with ketoprofen 50 mg . Treatment of headache with ketoprofen can start with 25 mg , and possibly less . 6 . Although a direct comparative study would be necessary to determine the relative benefits of the novel electronic patient diaries over traditional paper- and -pencil methods , this study has shown the usefulness of this newer technique to detect differences in efficacy between low doses of analgesics under ambulant conditions , with very limited loss of data . Electronic patient diaries appear to be an important new attribute for the efficacy assessment of self-medicated drugs UNLABELLED Reactive measures ( measures that change the phenomenon assessed ) cause problems in interpreting any changes observed . This study examined whether electronic daily diary measures of pain , activity interference , mood , and pain beliefs were reactive in terms of both observable data and patient-reported effects . Patients with chronic temporom and ibular disorder pain ( N = 71 , 86 % female ) completed electronic diaries 3 times daily for approximately 2 weeks and subsequently reported perceived effects on symptom-related variables . Seventy-three percent of patients reported that the assessment affected their pain , whereas 51 % , 45 % , and 39 % thought that it affected their daily activities , mood , and beliefs , respectively . In contrast , there was little objective evidence of reactivity as observed in the electronic diary ratings ; changes over 14 days were small ( eg , predicted changes on 0 to 10 scales : positive mood , .1 ; pain , -.3 ; perceived control , -.5 ) and not statistically significant . Subjective reactivity was generally not significantly related to objective reactivity . The data suggest that patients view daily assessment as having positive and negative effects on pain-related variables , but pain-related measures do not show reactive effects . PERSPECTIVE Electronic daily diary assessment methods hold the potential to increase knowledge concerning patients ' experiences with pain and sequential relations between pain-related variables , but only if the measurement process is nonreactive . This study provides evidence that electronic diary assessment of pain-related variables is nonreactive Objective : This study was design ed to compare 3 commonly used method ologies for assessing clinical pain during trials involving patients diagnosed with fibromyalgia syndrome . Baseline characteristics , characteristics over time , and compliance were evaluated for each of the methods . Methods : Fourteen patients diagnosed with fibromyalgia syndrome were asked to monitor their symptoms of pain using 3 different strategies over a 12-week period : 1 ) real-time pain reports were collected on an electronic diary using r and omly-scheduled audible prompts ; 2 ) end-of-week reports asked patients to rate their mean pain over the past week on the electronic diary ; and 3 ) monthly in-clinic reports asked patients to rate their mean pain for the week using a traditional paper and pencil diary . Results : Significantly different baseline values were obtained for the 3 methods . Paper and pencil produced the highest values , and real-time pain reports produced the lowest baseline values . Pain ratings were more likely to reflect decreases in the 2 methods relying on recall than the real-time strategy . The average adherence with pain monitoring using the electronic diary was 85 % , which was superior to the adherence for the recall measures completed during the clinic visits . Conclusion : Pain assessment methods relying on recall might contribute to an apparent improvement in clinical trials in the absence of an intervention ; such an effect has been considered a “ placebo response . ” Future clinical trials might consider using a real-time approach to pain assessment  , which in this study appeared to mitigate against seeing improvement in the absence of an intervention and demonstrated higher levels of patient adherence In an open three-center pilot study , 17 patients suffering from chronic persistent pain syndrome , due to osteoarthritis of the hip and knee or spondylarthrosis , were treated orally with 1800 - 2400 mg Ibuprofen per day for 3 weeks . The chronic pain syndrome and joint status were assessed by the physician at the beginning , and after 7 , 14 and 21 days . Self- assessment s were made by the patients six times daily during the full study period by means of battery-driven electronic diaries ( E.D. ) . The data entered by the patients were stored in the E.D. and after online transfer , processed and evaluated in a PC using appropriate software programs . E.D. were returned by 16 of 17 patients for evaluation . The technical functioning of the instrument was perfect ; its use was accepted by patients and physicians . The closely-meshed real-time recording of pain course and other subjective data , such as adverse events or medication , etc . , enables the physician to calculate more exactly and reliably improvement rates , as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates . By comparing different kinds of data , each entered at the same time , plausibility checks are possible . The procedure presented here is considered to be a new valuable tool for review ing subjective data from clinical drug trials Background : Therapy processes are complex dynamical systems where several variables are constantly interacting with each other . In general , the underlying mechanisms are difficult to assess . Our approach is to identify the dependency structure of relevant variables within the therapy process using interaction graphs . These are instruments for multivariate time series which are based on the analysis of partial spectral coherences . We used interaction graphs in order to investigate the therapy process of a multimodal therapy concept for fibromyalgia patients . Our main hypothesis was that self-efficacy plays a central role in the therapy process . Methods : Patients kept an electronic diary for 13 weeks .  Pain intensity , depression , sleep quality , anxiety and self-efficacy were assessed via visual analogue scales . The result ing multivariate time series were aggregated over individuals , and partial spectral coherences between each pair of the variables were calculated . From the partial coherences , interaction graphs were plotted . Results : Within the result ing graphical model , self-efficacy was strongly related to pain intensity , depression and sleep quality . All other relations were substantially weaker . There was no direct relationship between pain intensity and sleep quality . Conclusions : The relations between two variables within the therapy process are mainly induced by self-efficacy . Interaction graphs can be used to pool time series data of several patients and thus to assess the common underlying dependency structure of a group of patients . The graphical representation is easily comprehensible and allows to distinguish between direct and indirect relationships A new type of electronic pain diary was vali date d in an open , r and omized , crossover study . The main target variables were the comparison of the correctly realized pain assessment entries as well as the recording of the number of adverse events . Selected for the study were 20 patients , who were either hospitalized , partially-hospitalized or treated on an out-patient basis , with painful spondylogenic spinal syndrome or osteoarthritis of the trunk-proximal large joints . The patients were r and omly-assigned to the two groups . The first group initially received the conventional diary and thereafter the electronic diary ; the sequence was reversed for the second group . The drug therapy consisted of the NSAID , Ibuprofen , at an individually-adjusted dosage . Additional therapeutic measures were carried out by all the patients . The electronic pain diary proved to be equivalent to the conventional diary with regard to adherence of the pain assessment entry times . At a defined equivalence range of + /- 20 % , the statistical comparison showed that the limits were never exceeded . The equivalence test of And erson-Hauck showed a significance level of p less than 0.0001 . The minimum equivalence range was + /- 2 % . It therefore follows , that the conventional method of data recording can indeed be fully replaced by the electronic method . Comparing the individual data of the 16 patients , from whom entries with both the electronic as well as the conventional pain diaries were su bmi tted , a clear tendency for increased entries on adverse events in the electronic diary ( C.D. 6.4 + /- 10.5/E.D. 36.4 + /- 44.1 ) was demonstrated . No significant difference , however , was shown for the number of patients making data entries on adverse events in the electronic pain diary compared to those patients , who made their entries on adverse events in the conventional diary . According to the data from the physicians and patients , the  Ibuprofen treatment results in an improvement in 90%/75 % of cases , respectively . Likewise , the functional impairment of the affected joints as well as the swelling decreased markedly . The advantages of the electronic data recording system , i.e. closely-meshed controls can be carried out , transcriptional errors are minimized , data can be processed on-line , no possibility to subsequently change an entry , st and in contrast to the feature that there is no possibility to make free-style entries . The employment of the electronic system in the recording of individual data and subjective data represents a substantial improvement with regard to the quantity and quality of the data OBJECTIVE A growing body of evidence suggests that real-time electronic assessment s of pain are preferable to traditional paper- and -pencil measures . We used electronic assessment data derived from a study of patients with fibromyalgia ( FM ) to examine variability of pain over time and to investigate the implication s of pain fluctuation in the context of a clinical trial . METHODS The study group comprised 125 patients with FM who were enrolled in a r and omized , placebo-controlled trial of milnacipran .  Pain intensity levels  were captured in real time by participants using electronic diaries .  Variability in pain was assessed as the st and ard deviation of pain entries over time ( pain variability index [ PVI ] ) . RESULTS Substantial between-subject differences in pain variability were observed ( mean + /- SD PVI 1.61 + /- 0.656 [ range 0.27 - 4.05 ] ) . The fluctuation in pain report was constant over time within individuals ( r = 0.664 , P < 0.001 ) . Individuals with greater variability were more likely to be classified as responders in a drug trial ( odds ratio 6.14 , P = 0.006 ) ; however , this association was primarily attributable to a greater change in pain scores in individuals receiving placebo ( r = 0.460 , P = 0.02 ) rather than active drug ( r = 0.09 , P > 0.10 ) . CONCLUSION Among individuals with FM , there were large between-subject differences in real-time pain reports . Pain variability was relatively constant over time within individuals . Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo . It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions & NA ; We used patient daily electronic ratings of outcome ( activity interference , pain intensity , jaw use limitations , negative mood ) and process ( pain‐related beliefs , catastrophizing , and coping ) variables to evaluate a brief cognitive‐behavioral ( CB ) treatment for chronic temporom and ibular disorder ( TMD ) pain . TMD clinic patients ( N=158 ) were assigned r and omly to four biweekly sessions of either CB pain management training ( PMT ) or an education/attention control condition [ self‐care management ( SCM ) ] and were asked to complete electronic interviews three times daily for the 8‐week treatment . We analyzed diary data from 126 participants who completed > 50 % of requested interviews for > 6 weeks . Multilevel regression analyses indicated no statist 
    Output:
    
agent
Compliance was generally high , and positively associated with shorter diaries , age , having a user 's manual , financial compensation and using an alarm .
***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: 1 . The objective of this study was to investigate the efficacy of home-medicated non-steroidal anti-inflammatory ( NSAID ) analgesics , using an electronic patient diary . Single doses of ketoprofen 25 mg and ketoprofen 50 mg were compared with ibuprofen 200 mg and placebo in the treatment of a single occasion of episodic tension-type headache , using a double-blind , r and omized , parallel group design . 2 . A total of 166 patients with headache compatible with episodic tension-type headache and no refractory headaches or contraindications to NSAIDs  were contacted by advertisements and selected by question naires . Patients performed the study at home , using an electronic diary for headache assessment , with a form to allow comments and corrections . Visual analogue scales ( VAS 10 cm ) of headache severity , five-item headache relief rating ( HRR ) scales , and time of intake of ' escape ' analgesics were scored regularly , for 4 h following intake of trial medication . 3 . VAS-scores ( n = 1407 ) and HRRs ( n = 452 ) were returned by 159 patients . Of these scores , 1.5 % were inadvertently omitted from the electronic diary or modified on the comment forms . 4 . Headache ( VAS and HRR ) improved more with all three NSAIDs than with placebo , although the effect of ibuprofen was significant for HRR only . After 2 and 4 h respectively , the reduction in VAS-ratios was 17 and 19 % with placebo , 18 and 53 % with ibuprofen 200 mg , 41 and 61 % with ketoprofen 25 mg , and 47 and 59 % with ketoprofen 50 mg . After 4 h , headache improved strongly ( highest HRR ) in 18 % of patients on placebo , 39 % on ibuprofen 200 mg , 62 % on ketoprofen 25 mg , and 55 % on ketoprofen 50 mg . Headache disappeared completely ( VAS-score = 0 ) in one patient ( 3 % ) with placebo ( after 180 min ) , 10 % with ibuprofen 200 mg ( average 211 min ) , 18 % with ketoprofen 25 mg ( 159 min ) , and 28 % with ketoprofen 50 mg ( 146 min ) . 5 . The effects of ketoprofen 50 mg were more pronounced than those of ibuprofen 200 mg , which seemed to start later . Ketoprofen 25 mg and 50 mg were very similar , suggesting a maximal effect of the lower dose . Mild to moderate adverse events were reported by 9 % of the patients , half of which occurred with ketoprofen 50 mg . Treatment of headache with ketoprofen can start with 25 mg , and possibly less . 6 . Although a direct comparative study would be necessary to determine the relative benefits of the novel electronic patient diaries over traditional paper- and -pencil methods , this study has shown the usefulness of this newer technique to detect differences in efficacy between low doses of analgesics under ambulant conditions , with very limited loss of data . Electronic patient diaries appear to be an important new attribute for the efficacy assessment of self-medicated drugs UNLABELLED Reactive measures ( measures that change the phenomenon assessed ) cause problems in interpreting any changes observed . This study examined whether electronic daily diary measures of pain , activity interference , mood , and pain beliefs were reactive in terms of both observable data and patient-reported effects . Patients with chronic temporom and ibular disorder pain ( N = 71 , 86 % female ) completed electronic diaries 3 times daily for approximately 2 weeks and subsequently reported perceived effects on symptom-related variables . Seventy-three percent of patients reported that the assessment affected their pain , whereas 51 % , 45 % , and 39 % thought that it affected their daily activities , mood , and beliefs , respectively . In contrast , there was little objective evidence of reactivity as observed in the electronic diary ratings ; changes over 14 days were small ( eg , predicted changes on 0 to 10 scales : positive mood , .1 ; pain , -.3 ; perceived control , -.5 ) and not statistically significant . Subjective reactivity was generally not significantly related to objective reactivity . The data suggest that patients view daily assessment as having positive and negative effects on pain-related variables , but pain-related measures do not show reactive effects . PERSPECTIVE Electronic daily diary assessment methods hold the potential to increase knowledge concerning patients ' experiences with pain and sequential relations between pain-related variables , but only if the measurement process is nonreactive . This study provides evidence that electronic diary assessment of pain-related variables is nonreactive Objective : This study was design ed to compare 3 commonly used method ologies for assessing clinical pain during trials involving patients diagnosed with fibromyalgia syndrome . Baseline characteristics , characteristics over time , and compliance were evaluated for each of the methods . Methods : Fourteen patients diagnosed with fibromyalgia syndrome were asked to monitor their symptoms of pain using 3 different strategies over a 12-week period : 1 ) real-time pain reports were collected on an electronic diary using r and omly-scheduled audible prompts ; 2 ) end-of-week reports asked patients to rate their mean pain over the past week on the electronic diary ; and 3 ) monthly in-clinic reports asked patients to rate their mean pain for the week using a traditional paper and pencil diary . Results : Significantly different baseline values were obtained for the 3 methods . Paper and pencil produced the highest values , and real-time pain reports produced the lowest baseline values . Pain ratings were more likely to reflect decreases in the 2 methods relying on recall than the real-time strategy . The average adherence with pain monitoring using the electronic diary was 85 % , which was superior to the adherence for the recall measures completed during the clinic visits . Conclusion : Pain assessment methods relying on recall might contribute to an apparent improvement in clinical trials in the absence of an intervention ; such an effect has been considered a “ placebo response . ” Future clinical trials might consider using a real-time approach to pain assessment  , which in this study appeared to mitigate against seeing improvement in the absence of an intervention and demonstrated higher levels of patient adherence In an open three-center pilot study , 17 patients suffering from chronic persistent pain syndrome , due to osteoarthritis of the hip and knee or spondylarthrosis , were treated orally with 1800 - 2400 mg Ibuprofen per day for 3 weeks . The chronic pain syndrome and joint status were assessed by the physician at the beginning , and after 7 , 14 and 21 days . Self- assessment s were made by the patients six times daily during the full study period by means of battery-driven electronic diaries ( E.D. ) . The data entered by the patients were stored in the E.D. and after online transfer , processed and evaluated in a PC using appropriate software programs . E.D. were returned by 16 of 17 patients for evaluation . The technical functioning of the instrument was perfect ; its use was accepted by patients and physicians . The closely-meshed real-time recording of pain course and other subjective data , such as adverse events or medication , etc . , enables the physician to calculate more exactly and reliably improvement rates , as well as to carry out prognostic trend analyses and individual benefit-risk-ratio estimates . By comparing different kinds of data , each entered at the same time , plausibility checks are possible . The procedure presented here is considered to be a new valuable tool for review ing subjective data from clinical drug trials Background : Therapy processes are complex dynamical systems where several variables are constantly interacting with each other . In general , the underlying mechanisms are difficult to assess . Our approach is to identify the dependency structure of relevant variables within the therapy process using interaction graphs . These are instruments for multivariate time series which are based on the analysis of partial spectral coherences . We used interaction graphs in order to investigate the therapy process of a multimodal therapy concept for fibromyalgia patients . Our main hypothesis was that self-efficacy plays a central role in the therapy process . Methods : Patients kept an electronic diary for 13 weeks .  Pain intensity , depression , sleep quality , anxiety and self-efficacy were assessed via visual analogue scales . The result ing multivariate time series were aggregated over individuals , and partial spectral coherences between each pair of the variables were calculated . From the partial coherences , interaction graphs were plotted . Results : Within the result ing graphical model , self-efficacy was strongly related to pain intensity , depression and sleep quality . All other relations were substantially weaker . There was no direct relationship between pain intensity and sleep quality . Conclusions : The relations between two variables within the therapy process are mainly induced by self-efficacy . Interaction graphs can be used to pool time series data of several patients and thus to assess the common underlying dependency structure of a group of patients . The graphical representation is easily comprehensible and allows to distinguish between direct and indirect relationships A new type of electronic pain diary was vali date d in an open , r and omized , crossover study . The main target variables were the comparison of the correctly realized pain assessment entries as well as the recording of the number of adverse events . Selected for the study were 20 patients , who were either hospitalized , partially-hospitalized or treated on an out-patient basis , with painful spondylogenic spinal syndrome or osteoarthritis of the trunk-proximal large joints . The patients were r and omly-assigned to the two groups . The first group initially received the conventional diary and thereafter the electronic diary ; the sequence was reversed for the second group . The drug therapy consisted of the NSAID , Ibuprofen , at an individually-adjusted dosage . Additional therapeutic measures were carried out by all the patients . The electronic pain diary proved to be equivalent to the conventional diary with regard to adherence of the pain assessment entry times . At a defined equivalence range of + /- 20 % , the statistical comparison showed that the limits were never exceeded . The equivalence test of And erson-Hauck showed a significance level of p less than 0.0001 . The minimum equivalence range was + /- 2 % . It therefore follows , that the conventional method of data recording can indeed be fully replaced by the electronic method . Comparing the individual data of the 16 patients , from whom entries with both the electronic as well as the conventional pain diaries were su bmi tted , a clear tendency for increased entries on adverse events in the electronic diary ( C.D. 6.4 + /- 10.5/E.D. 36.4 + /- 44.1 ) was demonstrated . No significant difference , however , was shown for the number of patients making data entries on adverse events in the electronic pain diary compared to those patients , who made their entries on adverse events in the conventional diary . According to the data from the physicians and patients , the  Ibuprofen treatment results in an improvement in 90%/75 % of cases , respectively . Likewise , the functional impairment of the affected joints as well as the swelling decreased markedly . The advantages of the electronic data recording system , i.e. closely-meshed controls can be carried out , transcriptional errors are minimized , data can be processed on-line , no possibility to subsequently change an entry , st and in contrast to the feature that there is no possibility to make free-style entries . The employment of the electronic system in the recording of individual data and subjective data represents a substantial improvement with regard to the quantity and quality of the data OBJECTIVE A growing body of evidence suggests that real-time electronic assessment s of pain are preferable to traditional paper- and -pencil measures . We used electronic assessment data derived from a study of patients with fibromyalgia ( FM ) to examine variability of pain over time and to investigate the implication s of pain fluctuation in the context of a clinical trial . METHODS The study group comprised 125 patients with FM who were enrolled in a r and omized , placebo-controlled trial of milnacipran .  Pain intensity levels  were captured in real time by participants using electronic diaries .  Variability in pain was assessed as the st and ard deviation of pain entries over time ( pain variability index [ PVI ] ) . RESULTS Substantial between-subject differences in pain variability were observed ( mean + /- SD PVI 1.61 + /- 0.656 [ range 0.27 - 4.05 ] ) . The fluctuation in pain report was constant over time within individuals ( r = 0.664 , P < 0.001 ) . Individuals with greater variability were more likely to be classified as responders in a drug trial ( odds ratio 6.14 , P = 0.006 ) ; however , this association was primarily attributable to a greater change in pain scores in individuals receiving placebo ( r = 0.460 , P = 0.02 ) rather than active drug ( r = 0.09 , P > 0.10 ) . CONCLUSION Among individuals with FM , there were large between-subject differences in real-time pain reports . Pain variability was relatively constant over time within individuals . Perhaps the most important finding is that individuals with larger pain fluctuations were more likely to respond to placebo . It is not clear whether these findings are applicable only to patients with FM or whether they may also be seen in patients with other chronic pain conditions & NA ; We used patient daily electronic ratings of outcome ( activity interference , pain intensity , jaw use limitations , negative mood ) and process ( pain‐related beliefs , catastrophizing , and coping ) variables to evaluate a brief cognitive‐behavioral ( CB ) treatment for chronic temporom and ibular disorder ( TMD ) pain . TMD clinic patients ( N=158 ) were assigned r and omly to four biweekly sessions of either CB pain management training ( PMT ) or an education/attention control condition [ self‐care management ( SCM ) ] and were asked to complete electronic interviews three times daily for the 8‐week treatment . We analyzed diary data from 126 participants who completed > 50 % of requested interviews for > 6 weeks . Multilevel regression analyses indicated no statist 
    Output:
    