Objective To assess the effect of specialist palliative care on quality of life and additional outcomes relevant to patients in those with advanced illness. Design Systematic review with meta-analysis. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and trial registers searched up to July 2016. Eligibility criteria for selecting studies Randomised controlled trials with adult inpatients or outpatients treated in hospital, hospice, or community settings with any advanced illness. Minimum requirements for specialist palliative care included the multiprofessional team approach. Two reviewers independently screened and extracted data, assessed the risk of bias (Cochrane risk of bias tool), and evaluated the quality of evidence (GRADE tool). Data synthesis Primary outcome was quality of life with Hedges’ g as standardised mean difference (SMD) and random effects model in meta-analysis. In addition, the pooled SMDs of the analyses of quality of life were re-expressed on the global health/QoL scale (item 29 and 30, respectively) of the European Organization for Research and Treatment of Cancer QLQ-C30 (0-100, high values=good quality of life, minimal clinically important difference 8.1). Results Of 3967 publications, 12 were included (10 randomised controlled trials with 2454 patients randomised, of whom 72% (n=1766) had cancer). In no trial was integration of specialist palliative care triggered according to patients’ needs as identified by screening. Overall, there was a small effect in favour of specialist palliative care (SMD 0.16, 95% confidence interval 0.01 to 0.31; QLQ-C30 global health/QoL 4.1, 0.3 to 8.2; n=1218, six trials). Sensitivity analysis showed an SMD of 0.57 (−0.02 to 1.15; global health/QoL 14.6, −0.5 to 29.4; n=1385, seven trials). The effect was marginally larger for patients with cancer (0.20, 0.01 to 0.38; global health/QoL 5.1, 0.3 to 9.7; n=828, five trials) and especially for those who received specialist palliative care early (0.33, 0.05 to 0.61, global health/QoL 8.5, 1.3 to 15.6; n=388, two trials). The results for pain and other secondary outcomes were inconclusive. Some methodological problems (such as lack of blinding) reduced the strength of the evidence. Conclusions Specialist palliative care was associated with a small effect on QoL and might have most pronounced effects for patients with cancer who received such care early. It could be most effective if it is provided early and if it identifies though screening those patients with unmet needs. Systematic review registration PROSPERO CRD42015020674.

Opioid-induced constipation (OIC) is a frequent symptom in patients treated with opioids and impacts the patients' quality of life. However, there is no generally accepted definition for OIC. The aims of this study were to identify definitions for OIC in clinical trials and Cochrane Reviews and to compile assessment tools and outcome measures that were used in clinical trials. In a systematic review, 5 databases (MEDLINE, PubMed, The Cochrane Library, Web of Science, and EMBASE) were searched to identify clinical trials assessing OIC in adult patients or healthy volunteers. Studies published between 1993 and August 2013 were included. A total of 1488 studies were retrieved and 47 publications were included in the analysis. A minority of the publications (n=16, 34%) provided a clear definition for OIC. The definitions were highly variable and the present or recent history of opioid therapy was frequently (n=6, 38%) not included in these definitions. Of 46 clinical trials, 17 (37%) relied exclusively on objective measures such as bowel movement frequency, whereas another 17 studies additionally included patient-reported outcome measures such as, "feeling of incomplete bowel evacuation." Few trials (n=7, 15%) assessed the patient-reported global burden of OIC. Standard definitions and outcome measures are necessary (i) for consistency in OIC diagnosis in clinical practice and clinical trials; and (ii) to assure comparability of trial findings (eg, in meta-analyses). An OIC definition and outcome measures are proposed.

Analysis 2.1. Comparison 2 Nalfurafine versus placebo, Outcome 1 A) Pruritus on VAS scale (0-10 cm) in UP participants; parallel-group design; Wikström b: Wikström a (week 2) + period 1 Wikström b.. .. .. .. .. . Analysis 2.2. Comparison 2 Nalfurafine versus placebo, Outcome 2 A) Sensitivity analysis: random-effects model; pruritus on VAS scale (0-10 cm) in UP participants; parallel-group design; Wikström b: Wikström a (week 2) + period 1

IntroductionOpioid-induced constipation (OIC) is a frequent adverse event that impairs patients’ quality of life. This article evaluates the objective plus subjective efficacy and the safety of methylnaltrexone (MNTX) in OIC patients.MethodsRandomized controlled trials from a recent systematic review were included. In addition, a PubMed search was conducted for January 2014 to December 21, 2015. We included randomized controlled trials with adult OIC patients, MNTX as study drug, and OIC as primary outcome. Results were categorized in three outcome types: objective outcome measures (eg, time to laxation), patient-reported outcomes (eg, straining), and global burden measures (eg, constipation distress). Dichotomous meta-analyses with risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3. Only comparisons between MNTX and placebo were made.ResultsWe included seven studies with 1,860 patients. A meta-analysis revealed that patients under MNTX had considerably more rescue-free bowel movement within 4 hours after the first dose (RR 3.74, 95% CI 2.87 to 4.86; five studies, n=938; I2=0). Results of the review indicated that patients under MNTX had a higher stool frequency and needed less time to laxation compared with placebo. Moreover, patients receiving MNTX tended to have better values in patient-reported outcomes and global burden measures. Meta-analyses on safety revealed that patients under MNTX experienced more abdominal pain (RR 2.38, 95% CI 1.75 to 3.23; six studies, n=1,412; I2=60%) but showed a nonsignificant tendency in nausea (RR 1.27, 95% CI 0.90 to 1.78; six studies, n=1,412; I2=12%) and diarrhea (RR 1.45, 95% CI 0.94 to 2.24; five studies, n=1,258; I2=45%). The incidence of MNTX-related serious adverse events was 0.2% (4/1,860).ConclusionMNTX has been shown to be effective and safe. Future randomized controlled trials should consequently incorporate objective outcome measures, patient-reported outcomes, and global burden measures, and research the efficacy of MNTX in other populations, for example, patients under opioids after surgical procedures.

Finding a consensus definition and inclusion criteria for OIC plus a rational balance between efficacy and AEs of drugs remain future challenges.