***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: In a clinical trial of two antirheumatic agents  two methods of collection of side effects were used , one with and the other without a check list of possible symptoms . Findings suggested that the use of a check list interfered with the collection of side effects . Known side effects of aspirin — tinnitus , deafness , and gastrointestinal disturbance — were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used OBJECTIVE The authors sought to identify predictors of self-harm adverse events in treatment-resistant , depressed adolescents during the first 12 weeks of treatment . METHOD Depressed adolescents ( N=334 ) who had not responded to a previous trial with an SSRI antidepressant were r and omized to a switch to either another SSRI or venlafaxine , with or without cognitive behavior therapy .  Self-harm events , i.e. , suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants , and by systematic weekly assessment for the last 153 participants . RESULTS Higher rates of suicidal ( 20.8 % vs. 8.8 % ) and nonsuicidal self-injury ( 17.6 % vs. 2.2 % ) , but not serious adverse events ( 8.4 % vs. 7.3 % ) were detected with systematic monitoring . Median time to a suicidal event was 3 weeks , predicted by high baseline suicidal ideation , family conflict , and drug and alcohol use . Median time to nonsuicidal self-injury was 2 weeks , predicted by previous history of nonsuicidal self-injury . While there were no main effects of treatment , venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation . Adjunctive use of benzodiazepines , while in a small number of participants ( N=10 ) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events . CONCLUSIONS Since predictors of suicidal adverse events also predict poor response to treatment , and many of these events occurred early in treatment , improving the speed of response to depression , by targeting of family conflict , suicidal ideation , and drug use may help to reduce their incidence . The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution Summary The incidence of side-effects on administration of chloranolol ( Tobanum ® ) , a beta-adrenergic receptor blocking drug , to 2066 patients with hypertension , angina pectoris or arrhythmias was measured by three different methods . In 600 patients in an efficacy trial ( Group 1 ) both spontaneously reported complaints and objective signs were tabulated . A side effect — directed method , utilising a question naire containing a list of possible side-effects was also used , with the question naire being completed by the physician . 35 questions referred to anticipated and other side-effects . The trial was performed in two groups : in 537 patients a placebo was also given ( Group 2 ) , and in another set of 929 patients ( Group 3 ) the question naire inquiry was performed uncontrolled , without placebo .  All three groups were comparable in their distribution of sexes , ages and diagnoses , the mean daily dose of chloranolol its use alone or in combination , and in a similar duration of treatment . 55 % of all patients received chloranolol therapy for a period of more than 3 months . The ratio of in- and out patients was 1:5 . The side-effect incidence was independent of the age and sex of the patients and of the dose of chloranolol . The incidence was also unaffected whether chloranolol was used alone or in combination . The number of side-effects differed markedly between the three groups , their ratio was 1:10:24 in Groups 1 , 2 and 3 . Two-thirds of the side-effects subsided spontaneously within 1 month of their onset . The duration of the side-effects varied according to their character : cardiorespiratory side-effects were of the shortest duration and those affecting the central nervous system were the most enduring . The appreciable differences in incidence could be attributed to the methods of collection of the data . It has been stated that placebo controlled trials using a detailed question naire are the most suitable for estimating the incidence of side-effects ; recording side-effects spontaneously reported by patients are insufficiently sensitive , and uncontrolled trials using a question naire have been shown to be too sensitive . The revealed incidence of side effects leading to interruption of treatment is less affected by the method chosen . In 100 patients ( 4.8 % ) therapy had to be suspended because of the side-effects of chloranolol ( Group 1 : 1 % , Group 2 : 6.20 % , Group 3 : 6.6 % ) . Comparison of the incidence of cessation of therapy due to side-effects did not show an appreciable difference between the various beta-adrenergic receptor blocking agents , including chloranolol Introduction An increasing number of generic alendronate formulations have become available . Although expected to have the same tolerability and efficacy , head-to head comparison of generic and br and alendronate was never performed . Therefore , we compared the tolerability and efficacy of generic and br and alendronate . Methods In a r and omized double-blinded single centre cross-over study in 37 postmenopausal women ( mean age 65.4±6.4 years ) with osteoporosis were treated with generic and br and ed alendronate during 24 ( 2x12 ) weeks . Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale ( GSRS ) and self-reported side effects . Efficacy was assessed by serum bone turnover markers , carboxy terminal telopeptide ( CTX ) and procollagen type I N-terminal propeptide ( PINP ) . No wash out period was allowed ( ethical reasons ) . Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models . Results There were no significant differences in overall tolerance ( GSRS ) between treatment groups . However , for subscale abdominal pain , patients using generic had a significantly higher mean GSRS score at week 4 ( estimated mean difference ( B ) : 0.40 ; 95%CI : 0.05 to 0.74 , p = 0.024 ) . The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and br and ed alendronate ( p < 0.001 ) . Mean level of CTX was significantly lower with br and ed at week 4 ( B : 121.3 ; 95%CI : 52.0 to 190.5 ) , but not at week 12 ( B : 53.6 ; 95%CI:-3.7 to 110.9 ) . No significant differences were found for PINP at week 4 or 12 . Conclusions Bone turnover markers were significantly reduced with br and ed and generic alendronate . With br and ed , CTX was significantly lower at 4 weeks . Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment . Therefore , generic alendronate may not have the same tolerability and efficacy as br and ed alendronate in the first weeks after starting treatment in patients with a recent fracture . Trial Registration Dutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/ rct Background Historically , skin toxicity has been assessed in prospect i ve clinical trials using the clinician-reported National Cancer Institute Common Terminology Criteria for Adverse Events ( CTCAE ) . The patient-reported Skindex-16 measures symptoms and perceptions of toxicity . This study was design ed to compare information provided by these two measures . Methods Data were compiled from three placebo-controlled North Central Cancer Treatment Group studies ( N06C4 , N03CB , N05C4 ) having rash prevention as the primary objective . All used the Skindex-16 and CTCAE at baseline , weekly during treatment and during a minimum 2-week follow-up period . Statistical procedures , including Pearson correlations , were utilized to determine relationships between adverse event ( AE ) grade s and Skindex-16 scores . Results Four hundred and twelve individual patients provided data ( median age , 61 ; 134 male ) . Patients ' Skindex-16 score  results show a 0.9 overall mean ( range 0–6 with 6 being worse symptoms ) , a 0.4 baseline mean ( range , 0–4.3 ) and a 1.3 end-of-treatment mean ( range , 0–5.9 ) . Ninety-three , 142 and 177 patients experienced a grade 0 , 1 and 2 + CTCAE skin toxicity , respectively . Baseline Skindex-16 scores had relatively low correlation with CTCAE grade s. The correlation of rash grade with Skindex-16 scores ranged from r = 0.49 with the function subscale to r = 0.62 with the symptom subscale . The highest correlations of the maximum grade of any dermatological AE with the Skindex-16 were r = 0.48 for the total score and r = 0.55 for the symptom subscale . Conclusions The data reported support the decision to include both measures in a clinical trial to assess the patient experience , as each measure may specifically target varying symptoms and intensities Introduction Dose-limiting neurotoxicity is a major side effect of oxaliplatin treatment , producing initial acute neurotoxicity and chronic neuropathy with increasing exposure . The improvement in survival for patients with early-stage colorectal cancer treated with oxaliplatin  has highlighted the need for valid and reliable assessment of peripheral neuropathy . Objectives The objective of this paper was to explore neuropathic symptoms in oxaliplatin-treated patients as assessed using different methods . Methods Consecutive symptomatic patients reporting peripheral neuropathy after oxaliplatin chemotherapy for colorectal cancer were interviewed using a semi-structured clinical interview .  Neurotoxicity was also assessed using the  National Cancer Institute Common Toxicity Criteria scale ( clinician-rated ) , patient ‘ self-report ’ question naires ( PNQ ) , nerve conduction and clinical assessment . Results Twenty patients were assessed , 12.6 ± 2.8 months after treatment cessation ( mean cumulative oxaliplatin dose , 789 mg/m2 ) . In 40 % of patients , neurotoxicity necessitated early cessation of treatment . Only 10 % of patients were design ated by clinicians with severe neurotoxicity , whilst , in contrast , patient interviews and self-report question naires described significant physical limitations due to neuropathic symptoms in 60 % of patients . The majority ( 85 % ) of patients had objective evidence of sensory neuropathy with nerve conduction studies . Reports from clinical interviews were strongly correlated with patient self- assessment ( Pearson coefficient = 0.790 , p < 0.0005 ) . Conclusion Given the discrepancies in symptom prevalence highlighted by these findings , the monitoring of oxaliplatin-induced neurotoxicity would benefit from more informative clinical assessment , with inclusion of patient-reported outcome measures . Such an approach would be beneficial in a clinical trial setting to monitor the efficacy of interventions and in prospect i ve studies of survivorship to determine the true burden of peripheral neuropathy in oxaliplatin-treated patients Summary 251 patients from 23 primary health care centres were recruited to a clinical trial in which either felodipine or placebo was added to baseline metoprolol treatment . Three methods of symptom reporting were used in 191 patients , namely two previously documented self-administered question naires and an adverse event monitoring system ( spontaneous reports to treating physician).Higher frequencies of symptoms were seen with the question naires compared to spontaneous reporting . However , the overlap between the methods was moderate and they were found to complement one another . The question naires were completed twice during the study and the adverse event monitoring system was applied on five occasions . The rate of application had consequences for the ability of each method to detect transient , dose-related symptoms , e.g. headache and dizziness . Regardless of method , the possibility of detecting dose-related symptoms was enhanced when symptoms were measured not only during active treatment but also during a run-in or other baseline period , and both phases were considered in the analyses BACKGROUND A relative lack of extrapyramidal symptoms ( EPS , i.e. , the syndromes of dystonia , parkinsonism , akathisia , dyskinesia ) is one criterion used to determine whether an antipsychotic is " atypical . " The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospect i ve clinical trials . METHOD Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine ( 5 to 20 mg/day ) and 810 patients treated with haloperidol ( 5 to 20 mg/day ) for up to 6 weeks of therapy . Patients were monitored weekly by three methods of extrapyramidal symptom assessment : ( 1 ) detection of extrapyramidal adverse events ( signs and symptoms ) by casual observation , nonprobing inquiry , and spontaneous report ; ( 2 ) objective rating scale scores : and ( 3 ) use of concomitant anticholinergic medications . Emergence of EPS was assessed by ( 1 ) analysis of the incidence of extrapyramidal syndrome categories based on adverse events , ( 2 ) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores , ( 3 ) analysis of mean maximum change in rating scale scores , and ( 4 ) categorical analysis of antich 
    Output:
    
Despite different design s , population s and details of question ing methods , the narrative review showed that more specific question ing of participants led to more AEs detected compared to a more general enquiry .
This review supports concerns that methods to elicit participant-reported AEs influence the detection of these data .
There was a risk for under-detection of AEs in studies using a more general elicitation method compared to those using a comprehensive method .
These AEs may be important from a clinical perspective or for patients .
This under-detection could compromise ability to pool AE data .