***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 & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate  percentage  pain reduction  for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy BACKGROUND The long-term use of opioid analgesic drugs to treat chronic non-cancer pain ( CNCP ) is a major component of pain pharmacotherapy . The interpretation of the evidence concerning its efficacy and risks is currently debated . METHODS An interdisciplinary evidence - and consensus-based S3 guideline was up date d on the basis of a systematic literature search ( CENTRAL , Medline , and Scopus data bases , from October 2008 to October 2013 ) ; meta-analyses of r and omized controlled trials ( ≥ 4 weeks ) ; and a consensus procedure , as specified by the AWMF regulations , including 22 medical and psychological societies and 2 patient self-help organizations . RESULTS 119 publications were used to up date the guideline , and 6 systematic review s with meta-analyses were performed . A nominal group process was used to formulate recommendations concerning the indications and contraindications for the treatment of CNCP with opioid analgesics and the manner in which such treatments should be carried out . Opioid analgesics are an option for the short-term treatment ( 4 - 12 weeks ) of chronic pain due to osteoarthritis ( pain intensity , st and ardized mean difference [ SMD ] : -0.22 and -0.26 ) , diabetic polyneuropathy ( SMD -0.74 ) , post-herpetic neuralgia ( SMD -0.58 ) , and chronic low back pain ( SMD : -0.29 and -0.74 ) . Long-term opioid treatment ( ≥ 26 weeks ) for these diseases benefits only about 25 % of patients . For other conditions , either short- or long-term treatment with opioid analgesics should be considered an individual therapeutic trial . Opioid treatment for pain is contraindicated by primary headaches and by any functional or mental disorder of which pain is a leading manifestation . CONCLUSION To minimize the risks of opioid analgesic treatment , physicians must be aware of its contraindications and must regularly reassess its efficacy and side effects . Pharmacotherapy should be combined with other types of treatment OBJECTIVE This article describes the rationale and design of the  Oxycodone Users Registry ( OUR ) study and lessons learned during study development and data collection . DESIGN The OUR study used a prospect i ve registry design . SETTING Sixty-five academic and private medical practice s across the United States , including both specialists and primary care setting s. PARTICIPANTS A total of 814 patients with 1 ) injury or trauma of the head , neck , back , chest , or extremities ; 2 ) fibromyalgia ; 3 ) arthritis ; 4 ) neuropathic pain ; 5 ) other back or neck pain ; or 6 ) postoperative pain following outpatient orthopedic surgery . INTERVENTIONS Patients received immediate-release oxycodone either as monotherapy or as combination therapy , starting within 3 days following the baseline visit and continuing as needed for at least 5 days . MAIN OUTCOME MEASURES Patient demographics and disease information were recorded at baseline . Follow-up assessment s at days 3 , 7 , 14 , 21 , and 28 included pain intensity , pain relief , opioid-related symptoms , a sleep scale , the Brief Pain Inventory-Short Form , and the Work Limitations Question naire-Short Form . Adverse events , medical re source utilization , and changes to the oxycodone prescription were recorded during the study . At the end of study treatment , patients rated global treatment satisfaction , how bothersome side effects were , and the most important factor that would discourage them from future oxycodone therapy . RESULTS This report describes the study design , rationale , and lessons learned . CONCLUSIONS Underst and ing the rationale , design , and lessons learned from the conduct of the OUR study provides insight that can used in future registry studies Abstract Objective : The first oxycodone once daily ( OOD ) has been developed and after successful pharmacokinetic characterization , therapeutic efficacy and safety were compared to an established oxycodone twice daily ( OTD : Oxygesic/OxyContin , Mundipharma ) . Design and methods : A r and omized , double-blind , multicenter , cross-over , non-inferiority study was conducted in patients ( n = 68 ) with chronic malignant or non-malignant pain . The new OOD was compared to OTD at identical total daily doses ( TDD : 40–120 mg/day ) employing intensive , five times daily current pain ( 0–100 mm visual analog scale , VAS ) and twice daily 12 h recalled pain assessment s as well as safety parameters such as nausea and sedation ( VAS ) over 5 days for each treatment ( after a 5 day run-in phase ) . Results : There was no significant difference in analgesic potency detected between the two treatments based on 95 % CI for difference in the daily mean current pain ( −2.09 mm VAS ) over 5 days , determined as −5.09 to 0.91 mm VAS . A difference ≤12 mm VAS indicated non-inferiority of OOD , i.e. lack of clinical ly relevant difference in analgesia . Intake of rescue medication had no effect on study results as evaluated by ANCOVA . The difference in adverse events ( AEs ) between the two treatments did not reach significance , as 19.1 % and 23.5 % of patients experienced treatment-related AEs while on OOD and OTD , respectively . Advantages for OOD regarding consistency of analgesia ( i.e. use of rescue medication , current and recalled pain ) and sedation did not reach statistical significance in this limited study population . Conclusion : Despite the small number of patients and short study duration , the results support the conclusion that new OOD is ( at least ) equivalent to established OTD regarding safety and efficacy 
    Output:
    
There is no r and omised trial evidence to support or refute the suggestion that oxycodone , alone or in combination with naloxone , reduces pain in fibromyalgia