The Management of Opioid-Induced Constipation in Cancer and Advanced Illness: A Meta-Analysis.

CONTEXT: Constipation is a common problem among patients with cancer. By some accounts, about 60% of cancer patients experience constipation. There is limited empirical evidence of the clinical effectiveness of pharmacologic agents in opioid-induced constipation in advanced diseases. OBJECTIVES: We sought to quantitatively summarize the therapeutic effectiveness of the pharmacologic means of managing opioid-induced constipation. METHODS: Randomized control trials (RCTs) identified from medical literature databases that reported quantitative measures of the effect of pharmacotherapeutic agents to treat opioid induced constipation in patients with cancers and other advanced illnesses were included in this study. A conventional random effects meta-analysis was conducted including >3 trials with the same exposure and outcome assessed, and a network-meta-analysis was conducted for all placebo-controlled trials. RESULTS: Eighteen studies that examined the effect of various pharmacotherapeutic agents were included. The medications were Methylnatrexone (N = 5), Naldemedine (N = 5), other conventional agents (N = 4) and herbal medicines (N = 4). In conventional meta-analysis, methylnaltrexone increased the proportion achieving rescue-free laxation by 2.68 fold (95% CI: 1.34, 5.37; P = 0.0054) within 4 hours of the administration compared to placebo. In network meta-analysis, the pooled RR of the pharmacotherapeutic agents on rescue-free bowel movements as 2.26 (95% CI: 1.52, 3.36) for methylnaltrexone, 1.58 (95% CI: 0.94, 2.66) for naldemedine, and 0.74 (95% CI: 0.45, 1.23) for polyethylene glycol, compared to placebo. CONCLUSION: Methylnatrexone and Naldemedine have currently shown promise in randomized trials concerning opioid-induced constipation in cancer and advanced illness. It is imperative that future research ascertain not just the relative therapeutic efficacy but also the cost-benefit analyses of these newer regimens with more commonly used and accessible laxatives.

Effect of intake of probiotics and probiotic fermented foods on clinical outcomes among people living with HIV: A systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to determine the effect of probiotics and of probiotic-fermented foods on CD4 T-cell count, viral load, anaemia and body mass index (BMI) among people living with HIV (PLHIV). METHODS: In this article, we systematically reviewed the evidence on the influence of probiotic supplementation on CD4 lymphocyte count, viral load and anaemia among PLHIV on highly active antiretroviral therapy (HAART) and those who were HAART-naive. Medical literature databases identified randomised trials and pre-post studies of probiotic supplementation and HIV-related outcomes, and random effects meta-analysis was conducted. RESULTS: The preponderance of the evidence suggests that probiotic supplementation only improved CD4 lymphocyte count modestly, with quantitatively greater impact among individuals who were HAART-naive compared to HAART-experienced individuals. Probiotic supplementation improved CD4 lymphocyte count by 53 cells/mm3 (95% CI: 22 to 85) from 18 studies. Probiotic supplementation however reduced haemoglobin concentration by -2.1 g/L (95% CI: -4.0 to -0.2). Although viral load remain unchanged in HAART-experienced participants following probiotic supplementation, HAART-naïve participants saw a decrease in viral load. There were too few studies on the impact of probiotic supplementation on viral load (N = 1). CONCLUSION: Probiotic supplementation resulted in a modest increase in CD4 lymphocyte count among HAART-naive individuals with no significant change observed among HAART-experienced ones. Viral load and haemoglobin concentration also remained unchanged following probiotic supplementation. Further rigorous and well-powered studies may evaluate the effect of probiotic supplementation on important clinical outcomes among PLHIV on HAART.

Nutrition counselling and clinical outcomes in HIV: A systematic review and meta-analysis.

BACKGROUND: People living with the HIV (PLHIV) are at an increased risk of various diseases due to a weakened immune system, particularly if they are naïve or poorly adherent to antiretroviral therapy (ART). Nutrients play a critical role in improving immune health, especially among this population. We systematically reviewed the evidence concerning the impact of nutritional counselling on the occurrence of important clinical outcomes among PLHIV. METHODS: Medical literature databases (PubMed, EMBASE and Web of Science) were searched from inception to October 2022 for relevant published studies (n = 12) of nutritional counselling and HIV-related outcomes in adults on ART. Random-effects meta-analyses were conducted when the exposure-outcome relationships were similar in three or more studies. RESULTS: Although the methodologies of nutritional intervention varied across all studies, overall, the evidence from the meta-analysis indicates a nsignificant positive association between nutrition counselling and improvements in CD4 cell count, body mass index and low-density lipoprotein concentration. However, the existing literature does not provide enough evidence to establish a significant impact of nutrition counselling on other immune, anthropometric, and metabolic outcomes including viral load, weight, and lean mass due to the differences in the study designs. CONCLUSION: Well-powered randomized controlled trials are needed that explore the effect of evidence-based, individualized nutrition counselling on HIV-related clinical outcomes.

Non-anaesthetist-administered ketamine for emergency caesarean section in Kenya: cost-effectiveness analysis.

OBJECTIVES: Lack of anaesthesia services is a frequent barrier to emergency surgeries such as caesarean delivery in Kenya. This study aimed to estimate the survival gains and cost-effectiveness of scaling up the Every Second Matters (ESM)-Ketamine programme that trains non-anaesthetist providers to administer and monitor ketamine during emergency caesarean deliveries. SETTING: Hospitals in Kenyan counties with low rates of caesarean delivery. PARTICIPANTS: Patients needing emergency caesarean delivery in settings without availability of standard anaesthesia service. INTERVENTIONS: Simulated scales up of the ESM-Ketamine programme over 5 years (2020-24) was compared with status quo. OUTCOME MEASURES: Cost of implementing the programme and corresponding additional emergency caesarean deliveries. Maternal and fetal/neonatal deaths prevented, and corresponding life-years gained due to increased provision of emergency caesarean procedures. Cost-effectiveness was assessed by comparing the cost per life-year gained of the ESM-Ketamine programme compared with status quo. RESULTS: Over 5 years, the expected gap in emergency caesarean deliveries was 157 000. A US$1.2 million ESM-Ketamine programme reduced this gap by 28 700, averting by 316 maternal and 4736 fetal deaths and generating 331 000 total life-years gained. Cost-effectiveness of scaling up the ESM-Ketamine programme was US$44 per life-year gained in the base case and US$251 in the most pessimistic scenario-a very good value for Kenya at less than 20% of per capita GDP per life-year gained. CONCLUSION: In areas of Kenya with significant underprovision of emergency caesarean delivery due to a lack of availability of traditional anaesthesia, an ESM-Ketamine programme is likely to enable a substantial number of life-saving surgeries at reasonable cost.