Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC.

OBJECTIVES: First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure. MATERIALS AND METHODS: Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS). RESULTS: A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis. CONCLUSIONS: Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.

Emotional journey of Asian mothers of premature infants who received pasteurised donor human milk: a qualitative study.

OBJECTIVE: To explore the effect of donor human milk usage on the emotional experience of mothers with premature infants in a multiracial Asian population. DESIGN: A qualitative descriptive study. Semistructured individual interviews were audio-recorded, transcribed and analysed using Braun and Clarke's process of thematic analysis. SETTING AND PATIENTS: Seventeen mothers whose premature infants received donor human milk in a level III neonatal intensive care unit. MAIN OUTCOME MEASURES: Perceptions of mothers whose premature infants received donor human milk. RESULTS: Mothers described their experience as a journey of acceptance with three sequential themes. 'Resistance to receiving somebody else's milk' was a process of overcoming initial hesitation and concerns. 'Recognising maternal limitations and baby's needs' depicted the mothers' struggles in reconciling their infant's milk demand and their low milk supply. 'Embracing benefits of donor human milk and acceptance with gratitude' illustrated the mothers' joy and gratitude to milk donors as they embraced benefits of donor human milk usage. Although participants had agreed to use of donor human milk after counselling, many still struggled with negative emotions of anxiety and guilt. Mothers of Muslim faith had additional concerns about milk kinship and religious permissibility of donor human milk. CONCLUSION: Mothers undergo a spectrum of complex emotions from initial hesitation to acceptance with gratitude, when their premature infants receive donor human milk. Some continue to struggle with negative emotions and require more support. By recognising their emotional responses, healthcare providers can support mothers in their breastfeeding journey with targeted counselling.

A systematic review and network meta-analysis of randomized controlled trials on choice of central venous access device for delivery of chemotherapy.

OBJECTIVE: Ensuring reliable central venous access with the fewest complications is vital for cancer patients receiving chemotherapy. A systematic review and network meta-analysis was conducted to compare the safety, quality of life, and cost-effectiveness of different types of central venous access devices (CVADs) for patients receiving chemotherapy. METHODS: The PubMed, EMBASE, and Cochrane databases were searched from inception to August 20, 2021 for randomized controlled trials comparing the various CVADs (ie, nontunneled central venous catheters [CVCs], peripherally inserted CVCs [PICCs], totally implantable venous access ports [TIVAPs], and tunneled CVCs). RESULTS: A total of 11 eligible randomized controlled trials of 2585 patients were identified. TIVAPs were associated with a lower odds of overall complications, device removal due to complications, and thrombotic and mechanical complications compared with PICCs (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.43-0.69; OR, 0.49; 95% CI 0.26-0.93; OR, 0.37; 95% CI, 0.23-0.62; and OR, 0.35; 95% CI, 0.13-0.95, respectively). Tunneled CVCs were associated with a higher odds of overall complications, device removal due to complications, and infective complications compared with TIVAPs (OR, 1.68; 95% CI, 1.30-2.17; OR, 2.52; 95% CI, 1.34-4.73; and OR, 2.11; 95% CI, 1.14-3.90, respectively). The ranking probability using the surface under the cumulative ranking curve values indicated that TIVAPs had the lowest probability of overall complications, removal due to complications, and thrombotic complications. CONCLUSIONS: TIVAPs were found to be superior in terms of complications and quality of life compared with other CVADs, without compromising cost-effectiveness, and should be considered the standard of care for patients receiving chemotherapy.

Breastfeeding in COVID-19: A Pragmatic Approach.

The novel coronavirus disease 2019 (COVID-19) pandemic has resulted in changes to perinatal and neonatal care, concentrating on minimizing risks of transmission to the newborn and health care staff while ensuring medical care is not compromised for both mother and infant. Current recommendations on infant care and feeding when mother has COVID-19 ranges from mother-infant separation and avoidance of human milk feeding, to initiation of early skin-to-skin contact and direct breastfeeding. Health care providers fearing risks of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) maternal-infant transmission may veer toward restricted breastfeeding practices. We reviewed guidelines and published literature and propose three options for infant feeding depending on various scenarios. Option A involves direct breastfeeding with the infant being cared for by the mother or caregiver. In option B, the infant is cared for by another caregiver and receives mother's expressed milk. In the third option, the infant is not breastfed directly and does not receive mother's expressed milk. We recommend joint decision making by parents and the health care team. This decision is also flexible as situation changes. We also provide a framework for counseling mothers on these options using a visual aid and a corresponding structured training program for health care providers. Future research questions are also proposed. We conclude that evidence and knowledge about COVID-19 and breastfeeding are still evolving. Our options can provide a quick and flexible reference guide that can be adapted to local needs. KEY POINTS: · SARS-CoV-2 is unlikely transmitted via human milk.. · A shared decision making on infant feeding is the preferred approach.. · Mothers can safely breastfeed with appropriate infection control measures..

Sodium-Glucose Co-Transporter 2 Inhibitors for Non-Alcoholic Fatty Liver Disease in Asian Patients With Type 2 Diabetes: A Meta-Analysis.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a very common disorder among patients with type 2 diabetes and may share causal relationship. Type 2 diabetes is a risk factor for progression and potential poor outcomes in NAFLD patients. This meta-analysis aimed to analyze the current evidence of sodium-glucose co-transporter-2 inhibitors (SGLT2i), a glucose-lowering drug to improve NAFLD in patients with Type 2 Diabetes. Methods: Medline, Embase and Cochrane Central Register of Controlled Trials were searched for articles examining efficacy of SGLT2i on treatments of NAFLD in type 2 diabetes in July 2020, and articles were sieved. Continuous data were extracted in the form of mean and standard deviation and were pooled with standardized mean difference (SMD). Results: 10 articles involving 555 patients from seven randomized controlled trials (RCTs) and three cohort studies, were included in this meta-analysis. Our analysis revealed significant improvements in hepatic fat content (after treatment: -0.789 (-1.404 to -0.175), p = 0.012; compared with control: -0.923 (-1.562 to -0.285), p = 0.005), AST (After Treatment: -0.539 (-0.720 to -0.357), p < 0.001; compared with control: -0.421 (-0.680 to -0.161), p = 0.001), ALT (after treatment: -0.633 (-0.892 to -0.373), p < 0.001; compared with Control: -0.468 (-0.685 to -0.251), p < 0.001), body composition (BMI: after treatment: -0.225 (-0.456 to 0.005), p = 0.055; compared with Control: -1.092 (-2.032 to -0.153), p = 0.023), glycemic control (HbA1c: After Treatment: -0.701 (-1.098 to -0.303), p = 0.001; compared with control: -0.210 (-0.603 to 0.183), p = 0.295), lipid parameters (Triglycerides: after treatment: -0.230 (-0.409 to -0.052), p = 0.011; compared with control: -0.336 (-0.597 to -0.076), p = 0.011), inflammatory markers (serum ferritin: after treatment: -0.409 (-0.694 to -0.124), p = 0.005; compared with control: -0.814 (-1.688 to 0.059), p = 0.068) after SGLT2i treatment, and when compared against controls. There was a trend in the improvement in fibrosis markers after SGLT2i treatment. Conclusions: SGLT2i is an effective treatment to improve NAFLD among patients with type 2 diabetes. Further studies are needed to understand the direct and indirect effects of SGLT2i on NAFLD and if SGLT2i could prevent the progression of NAFLD or NASH. SGLT2i could potentially be considered for patients with type 2 diabetes and NAFLD, if there are no contraindications.