Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1–5] vs. 1 [0–2], p < 0.01) and 42% opioid dose (35 [22–61] vs. 60 [40–80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58–0.82] vs. 0.51 [0.13–0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30–34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation.

Background: Chronic malnutrition is a condition that can have important negative impacts on subsequent physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The supplementation with small quantity lipid based nutrients (SQ-LNS) and the provision of cash transfers are promising interventions to prevent it but more operational research is needed to gain evidence on their effectiveness. Methods/Design: The Crescer project aims to evaluate the impact of a SQ-LNS intervention and a cash transfer intervention in the lineal growth of children less than 2 years old in Southern Angola. The three-arm parallel cluster randomised controlled trial is set in four comunas of Huila and Cunene provinces. Pregnant women are recruited, and treatment arms receive unconditional cash or SQ-LNS plus a food family ration for the first 1000 days, from pregnancy through the child reaching 24 months. A comparison group receives “standard of care” provided by the Crescer project to which all groups have the same access. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children’s age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children’s dietary diversity. Quantitative data are also collected on women’s empowerment, household food security, expenditure and relevant clinical and social events at base line, end line and intermediate time points. Discussion: The results of this trial will provide valuable information on the impact of a SQ LNS and an unconditional cash transfer intervention, carried out during the first 1000 days, in the children´s growth up to 2 years, and related outcomes. Trial registration: Clinical Trials NCT05571280. Registered 7 October 2022.