Pharmacological prevention and treatment of opioid-induced constipation in cancer patients: A systematic review and meta-analysis.

BACKGROUND: Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients. METHODS: A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed. RESULTS: Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I2 = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I2 = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I2 = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I2 = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates. CONCLUSIONS: Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.

The (cost-)effectiveness of combined lifestyle interventions for people with persistent low-back pain who are overweight or obese: A systematic review.

INTRODUCTION: Lifestyle factors are expected to contribute to the persistence and burden of low-back pain (LBP). However, there are no systematic reviews on the (cost-)effectiveness of combined lifestyle interventions for overweight or obese people with LBP. AIM: To assess whether combined lifestyle interventions are (cost-)effective for people with persistent LBP who are overweight or obese, based on a systematic review. DESIGN: Systematic review METHOD: PubMed, Cochrane, Embase, CINAHL, PsycINFO and the Wiley/Cochrane Library were searched from database inception till January 6th 2023. Two independent reviewers performed study selection, data-extraction and risk of bias scoring using the Cochrane RoB tool 2 and/or the Consensus Health Economic Criteria list. GRADE was used to assess the level of certainty of the evidence. RESULTS: In total 2510 records were screened, and 4 studies on 3 original RCTs with 216 participants were included. Low certainty evidence (1 study) showed that combined lifestyle interventions were not superior to usual care for physical functioning, pain and lifestyle outcomes. Compared to usual care, moderate certainty evidence showed that healthcare (-$292, 95%CI: 872; -33), medication (-$30, 95% CI -65; -4) and absenteeism costs (-$1000, 95%CI: 3573; -210) were lower for the combined lifestyle interventions. CONCLUSION: There is low certainty evidence from 3 studies with predominantly small sample sizes, short follow-up and low intervention adherence that combined lifestyle interventions are not superior to physical functioning, pain and lifestyle outcomes compared to usual care, but are likely to be cost-effective.

How to improve inpatient sleep in regular care wards: a systematic review and meta-analysis of sleep disturbers and non-pharmacological interventions.

OBJECTIVE: To determine factors affecting inpatient sleep and assess the range and effectiveness of non-pharmacological interventions aimed at improving the sleep of patients admitted to regular care wards. METHODS: A systematic literature search was conducted in five scientific databases, including articles published from inception to June 23rd, 2023. Eligible studies evaluated sleep disturbing factors or the effect of non-pharmacological intervention(s). Meta-analyses on intervention studies were conducted using a random effects model. Certainty of evidence was assessed using the GRADE approach. RESULTS: Out of 591 potentially eligible studies, 229 were included in this review. Sleep disturbers were identified in 153 studies, and 102 studies were eligible for meta-analysis. Common factors contributing to poor sleep included noise, light, care-related interruptions, pain, and anxiety. The meta-analyses revealed large pooled effects in favor of sleep for the use of eye masks and earplugs, headphones and white noise, aromatherapy, massage, muscle relaxation and breathing exercises, and advanced nursing strategies. However, the certainty of the evidence ranged from moderate to very low. CONCLUSION: Inpatient sleep is often disturbed by patient-related, care-related, and environmental factors. While there are promising non-pharmacological interventions, the overall quality of studies, heterogeneity in study populations, and differences in outcome measures present challenges for drawing definitive conclusions.

[18F]FDG-PET/CT in Staphylococcus aureus bacteremia: a systematic review.

OBJECTIVES: [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB. METHODS: We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley's Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case-control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers. RESULTS: We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed. DISCUSSION: We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions.