***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: Background Opioid-induced constipation ( OIC ) is one of the major symptoms in palliative care with a prevalence of 30 - 50 % . Methylnaltrexone for the treatment of OIC is significantly more effective than placebo , but only in about fifty percent of the patients regardless of dose increase . Dose increases cause increased toxicity without additional efficacy , and are therefore not recommended . While methylnaltrexone is a μ-receptor antagonist , only a few opioids are solely μ-receptor agonists . Therefore , the response to methylnaltrexone may be determined by the receptor-profile of a specific opioid . In addition , methylnaltrexone may also affect the immune system and angiogenesis as was found in pre- clinical studies . Primary aim of this study is to determine differences in the efficacy of methylnaltrexone prescribed to resolve opioid induced constipation between three commonly used opioid subtypes : morphine sulphate , oxycodone and fentanyl . Secondary aim is to explore potential immunomodulatory and antiangiogenic effects of methylnaltrexone . Methods In this multi-center , prospect i ve , parallel group trial we will evaluate the efficacy of methylnaltrexone in resolving OIC occurring as a side effect of the most common opioid subtypes : morphine , oxycodone and fentanyl . In total 195 patients with OIC despite prophylactic laxatives will receive methylnaltrexone every other day up to fourteen days . Patients will report its effect in a laxation diary . Group allocation is based on the opioid type the patient is using . At the start and end of the study period patients complete the Bowel Function Index question naire . A subgroup of the patients will donate blood for analysis of immunomodulatory- and anti-angiogenic effects of methylnaltrexone . Discussion In this study we aim to determine the efficacy of methylnaltrexone per opioid subtype to reduce constipation . We expect that the outcome of this study will improve the clinical use of methylnaltraxone . Trial registration This trial is registered at clinical trials.gov : NCT01955213 and in the Dutch trial register : NTR4272 The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . A dose-ranging study of the use of oral naloxone in opioid-related constipation in patients with far-advanced cancer is reported . Naloxone doses were calculated as a percentage of the morphine dose each patient was receiving . Seventeen patients entered the first phase of the study , which had a r and omised , double-blind design . Outcome measures were small bowel transit time ( SBTT ) measured by the lactulose/hydrogen breath test , pain scores and the occurrence of adverse events .  One subject was excluded before receiving naloxone . No significant difference between placebo and naloxone occurred in the 14 remaining patients receiving total daily doses of naloxone 10 % or less of the 24 h dose of morphine . Two further patients experienced a marked laxative effect with naloxone at 20 % of the 24 h dose of morphine . In one of these , SBTT was available and was unchanged from placebo . The other declined to continue with SBTT measurement . Phase two of the study had an open design , in which laxative effects were determined clinical ly . Naloxone at a maximum dose level of 20 % was given to seven patients , up to 40 % to two patients and up to 80 % to one patient . Four out of the seven patients in the 20 % dose level group , and all of the remainder , experienced laxative effects . Two patients experienced symptoms of opioid withdrawal , one of whom also had return of pain . It is concluded that oral naloxone at a daily dose of 20 % or more of the prevailing 24 h morphine dose is a potentially valuable therapy for opioid- related constipation . However , opioid withdrawal was observed and it is suggested that initial individual naloxone doses should not exceed 5 mg . Further research is needed into the oral absorption of naloxone , as well as further studies of clinical efficacy and dosing Methylnaltrexone , a peripherally-acting quaternary opioid antagonist , is an investigational treatment for  opioid-induced constipation in patients with advanced illness . This r and omized , parallel-group , repeated dose , dose-ranging trial included a double-blind phase for one week followed by an open-label phase for a maximum of three weeks . Opioid-treated patients with advanced illness who met criteria for opioid-induced constipation despite laxative therapy were potentially eligible . Double-blind treatment occurred on Days 1 , 3 , and 5 ; open-label therapy could be administered as often as every other day . The initial dose range of 1 mg , 5 mg , or 12.5 mg was extended by adding a 20 mg group during the study while still maintaining the double blind ; the initial open-label dose of 5 mg could be titrated . The primary outcome was a laxation response within four hours after the first dose . Thirty-three patients received at least one dose of methylnaltrexone . Only one of 10 patients ( 10 % ) who received the 1 mg dose experienced laxation within four hours of dosing . The median time to laxation was > 48 hours for the 1 mg dose group , compared to 1.26 hours for all patients receiving > or=5 mg ( P=0.0003 ) . There was no apparent dose-response above 5 mg . Most adverse events were related to the gastrointestinal system , were mild , and did not lead to discontinuation . In conclusion , methylnaltrexone relieved opioid-induced constipation at doses > or=5 mg in patients with advanced illness , and did not reduce analgesia or cause opioid withdrawal symptoms Methylnaltrexone , a peripheral mu-opioid receptor antagonist with restricted ability to cross the blood-brain barrier , may relieve  opioid-induced constipation ( OIC ) without reversing analgesia . A total of 154 patients with advanced illness and OIC enrolled in a double-blind , r and omized , placebo-controlled trial , with optional open-label phases ( up to 4 months ) in hospice and palliative care centers during 2003 - 2005 . They received a single subcutaneous injection of methylnaltrexone ( 0.15 mg/kg or 0.3 mg/kg ) or placebo . Laxation response within 4 hours was 62 % and 58 % for methylnaltrexone 0.15 mg/kg and 0.3 mg/kg , respectively , compared with 14 % for placebo ( P < 0.0001 ; each dose vs placebo ) . Approximately half of the methylnaltrexone responders defecated within 30 minutes of dosing . Open-label phase response rates mirrored those for methylnaltrexone during the double-blind phase . There was no change in pain scores or evidence of central opioid withdrawal . The most common adverse events ( AEs ) were abdominal pain and flatulence . Three patients had serious AEs attributed to methylnaltrexone . Subcutaneous methylnaltrexone was efficacious in rapidly inducing laxation and was generally well tolerated in patients with advanced illness and OIC Postoperative ileus ( POI ) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication . Ileus causes a variety of symptoms including bloating , pain , nausea , and vomiting , but particularly delays tolerance of oral diet and liquids . Thus POI is a primary determinant of hospital stay after surgery . ‘ Fast-track ’ recovery protocol s , opioid sparing analgesia , and laparoscopic surgery reduce but do not eliminate postoperative ileus . Alvimopan is a mu opioid receptor antagonist that blocks the effects of opioids on the intestine , while not interfering with their central ly mediated analgesic effect . Several large r and omized clinical trials have demonstrated that alvimopan accelerates the return of gastrointestinal function after surgery and subsequent hospital discharge by approximately 20 hours after elective open segmental colectomy . However , it has not been tested in patients undergoing laparoscopic surgery and is less effective in patients receiving nonsteroidal anti-inflammatory agents in a narcotic sparing postoperative pain control regimen . Safety concerns seen with chronic low dose administration of alvimopan for opioid bowel dysfunction have not been noted with its acute use for POI Objective : An examination of whether oxycodone/naloxone prolonged-release tablets ( OXN PR ) can improve constipation and maintain analgesia , compared with oxycodone prolonged-release tablets ( OxyPR ) in patients with moderate/severe cancer pain . Methods : R and omized , double-blind , active-controlled , double-dummy , parallel-group study in which 185 patients were r and omized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks . Efficacy assessment s included Bowel Function Index ( BFI ) , Brief Pain Inventory Short-Form ( BPI-SF ) , laxative and rescue medication use . Quality of life ( QoL ) and safety assessment s were conducted . Results : After 4 weeks , mean BFI score was significantly lower with OXN PR ; mean total laxative intake was 20 % lower with OXN PR . Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable . QoL assessment s were stable and comparable with greater improvements in constipation-specific QoL assessment s with OXN PR . Overall , rates of adverse drug reactions were similar . Conclusions : OXN PR provides superior bowel function in cancer pain patients , compared with OxyPR , without compromising analgesic efficacy or safety . This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients Abstract Background : Subcutaneous methylnaltrexone ( MNTX ) , dosed based on body weight , is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation ( OIC ) ; however , fixed-dose administration of MNTX may improve ease of administration . Objective : The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials . Methods : In a double-blind , r and omized , placebo-controlled trial ( RCT ) , patients with advanced illness and OIC received MNTX ( 8 mg or 12 mg by body weight [ 38 kg to < 62 kg or ≥62 kg , respectively ] ) or placebo every other day ( QOD ) for two weeks . Patients completing the RCT could enroll in an open-label extension ( OLE ) study with MNTX administered as needed ( PRN ) . The primary endpoint was percentage of patients with a rescue-free bowel movement ( RFBM ) within four hours after ≥2 of the first 4 doses in the first week . Results : In the RCT , 116 and 114 patients received MNTX and placebo , respectively , and 149 patients continued to the OLE study . The percentage of patients achieving primary endpoint was 62.9 % and 9.6 % for MNTX and placebo groups , respectively ( p<0.0001 ) . Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups , respectively ( p<0.0001 ) . Efficacy results during the OLE study were consistent with the RCT . MNTX demonstrated a favorable safety profile in the RCT and OLE study . Conclusion : Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness Background and objectives : Opioid-induced constipation can have a major negative impact on patients ’ quality of life . This r and omised clinical trial evaluated patient assessment of the efficacy and tolerability of oral prolonged-release ( PR ) oxycodone when co-administered with oral naloxone PR . Methods : Two hundred and two patients with chronic cancer- or non-cancer-related pain undergoing stable oxycodone PR therapy ( 40 , 60 or 80 mg/day ) were r and omised to one of four intervention groups : 10 , 20 or 40 mg/day naloxone PR or placebo . Following a 4-week maintenance phase , patients were followed-up for 2 weeks in which time they received oxycodone PR only . At the end of the maintenance phase , patients and investigators were asked to assess treatment efficacy and tolerability , as well as preference for the titration or maintenance phase . Results : Patient and investigator global assessment of efficacy and tolerability improved with increasing naloxone dose . Efficacy was ranked as ‘ good ’ or ‘ very good ’ by 50.0 % , 67.4 % and 72.5 % of patients in the 10 , 20 and 40 mg naloxone PR dose groups , respectively , compared with 43.5 % of patients in the placebo group . Patient assessment of tolerability was similar between treatment groups and placebo , being ranked as ‘ good ’ or ‘ very good ’ by 83.3 % , 79. 
    Output:
    
There was moderate- quality evidence that naldemedine had no effect on opiate withdrawal .
There was moderate- quality evidence that the rate of opioid withdrawal was not affected .
For early laxation , there was low- quality evidence of no clear difference between doses on analgesia and adverse events .
There is moderate- quality evidence to suggest that , taken orally , naldemedine  improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events .
The conclusions on naloxone and methylnaltrexone have not changed .
There is moderate- quality evidence that methylnaltrexone  improves bowel function in people receiving palliative care in the short term and over two weeks , and low- quality evidence that it does not increase adverse events .
None of the current trials evaluated effects in children