Real-world efficacy of low dose osimertinib as second-line treatment in patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer.

Background: Response rates of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) to lower doses of osimertinib [20 mg once daily (OD) and 40 mg OD] are similar to those of the recommended dose of 80 mg OD, but there is a lack of real-world evidence on the effect of the lower doses of osimertinib on survival outcomes. We conducted this study to assess the efficacy and safety of lower osimertinib doses for patients with EGFR-mutated advanced NSCLC whose disease had progressed on earlier generation EGFR tyrosine kinase inhibitors (TKIs) in a real-world clinical practice. Methods: This multicenter, retrospective study included patients with EGFR-mutated advanced NSCLC treated with low doses of osimertinib after failing first- or second-generation EGFR TKIs due to acquired T790M mutation. Data on demographics, staging, treatment history, best overall response rate (ORR) based on RECIST 1.1, and adverse events (AEs) were collected from the patients' case notes. Descriptive data were described in percentages and medians. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: Of the 22 patients studied [males =8 and females =14; Eastern Cooperative Oncology Group (ECOG) 1 or 2 =7 and ECOG 3 or 4 =15], 45.5% were on 40 mg OD, 31.8% were on 80 mg every other day (EOD), and 22.7% on 40 mg EOD. First-line EGFR TKIs used included afatinib, erlotinib, and gefitinib. The ORR with lower doses of second-line osimertinib was 77.3%. Overall, the median PFS was 10.0 months [95% confidence interval (CI): 8.6-11.4] and median OS was 13.0 months (95% CI: 9.4-16.6). In patients with ECOG 1 or 2, the median PFS was 18.0 months (95% CI: 5.8-30.2) and the median OS was not reached at the time of analysis. In patients with poor ECOG performance status of 3 and 4, good survival outcomes were also seen with a median PFS of 7.0 months (95% CI: 4.7-9.3) and median OS of 10.0 months (95% CI: 7.5-12.5). All AEs except one case of paronychia were Grade 1. There were no Grade 3 or 4 AEs. Conclusions: Treatment with low dose osimertinib demonstrated good efficacy and tolerability in EGFR-mutated advanced NSCLC patients who failed first-line treatment with first- or second-generation EGFR TKIs due to T790M mutation.

The Clinical Characteristics and Outcomes of Infantile Seizures in the First Year of Life: A Single-Center Study.

BACKGROUND: Epilepsy has a high incidence among infants during their first year of life, yet the prognosis can vary significantly. Although considerable research has been conducted on infantile spasms, studies examining infantile-onset epilepsy, excluding infantile spasms, remain limited, particularly concerning the factors influencing outcomes. Therefore, our study aims to elucidate seizure control, developmental outcomes, and prognostic factors in infants with epilepsy during their first year of life, within a single-center study in Malaysia. METHODS: We retrieved data from patients who experienced seizures before age 12 months and were followed for over two years, using electronic patient records at Hospital Raja Perempuan Zainab II in Kelantan, a state in Malaysia's east coast. We retrospectively reviewed these records and assessed clinical outcomes based on the last follow-up. RESULTS: Of 75 patients, 61 (81.3%) achieved good seizure control or remission. At the last follow-up, 24 (32%) exhibited developmental delay, whereas 19 (25.3%) displayed abnormal neuroimaging. Patients with abnormal background electroencephalographic (EEG) activity, as well as abnormal radiological findings, were more likely to experience poor seizure control and unfavorable developmental outcomes (P < 0.05). CONCLUSIONS: Our study underscores that most infants with epilepsy can achieve seizure remission. However, poor seizure control and developmental delay are associated with abnormal EEG background and characteristics, as well as neuroimaging abnormalities. The management of infantile-onset epilepsies may necessitate substantial resources and precise interventions to enhance overall outcomes.

Real-World Treatment and Outcomes of ALK-Positive Metastatic Non-Small Cell Lung Cancer in a Southeast Asian Country.

Purpose: Anaplastic lymphoma kinase (ALK) inhibitors are associated with good overall survival (OS) for ALK-positive metastatic non-small cell lung cancer (NSCLC). However, these treatments can be unavailable or limited by financial constraints in developing countries. Using data from a nationwide lung cancer registry, the present study aimed to identify treatment patterns and clinical outcomes of ALK-positive NSCLC in Malaysia. Methods: This retrospective study examined data of patients with ALK-positive NSCLC from 18 major hospitals (public, private, or university teaching hospitals) throughout Malaysia between January 1, 2015 and December 31, 2020 from the National Cardiovascular and Thoracic Surgical Database (NCTSD). Data on baseline characteristics, treatments, radiological findings, and pathological findings were collected. Overall survival (OS) and time on treatment (TOT) were calculated using the Kaplan-Meier method. Results: There were 1581 NSCLC patients in the NCTSD. Based on ALK gene-rearrangement test results, only 65 patients (4.1%) had ALK-positive advanced NSCLC. Of these 65 patients, 59 received standard-of-care treatment and were included in the analysis. Crizotinib was the most commonly prescribed ALK inhibitor, followed by alectinib and ceritinib. Patients on ALK inhibitors had better median OS (62 months for first-generation inhibitors, not reached at time of analysis for second-generation inhibitors) compared to chemotherapy (27 months), but this was not statistically significant (P=0.835) due to sample-size limitations. Patients who received ALK inhibitors as first-line therapy had significantly longer TOT (median of 11 months for first-generation inhibitors, not reached for second-generation inhibitors at the time of analysis) compared to chemotherapy (median of 2 months; P<0.01). Conclusion: Patients on ALK inhibitors had longer median OS and significantly longer TOT compared to chemotherapy, suggesting long-term benefit.

Near-Complete Whole-Genome Sequencing of Two Burkholderia pseudomallei Strains Harbouring Novel Molecular Class D Beta-Lactamase Genes, Isolated from Malaysia.

Here, we present two 7.1- and 7.3-bp near-complete genome sequences of Burkholderia pseudomallei strains of HTAA077 and HRPB058, isolated from a pus culture from a confirmed melioidosis patient at Hospital Tengku Ampuan Afzan, Kuantan, Malaysia, and from blood culture from a patient at Hospital Raja Permaisuri Bainun, Ipoh, Malaysia, using a Nanopore MinION instrument.

Outcomes of Patients with EGFR-Mutant Advanced NSCLC in a Developing Country in Southeast Asia.

Background: Although first- and second-generation EGFR TKIs are considered first-line treatment in EGFRm+ NSCLC, most patients develop resistance and progress, commonly, EGFR T790M mutation. The third-generation EGFR-TKI has demonstrated efficacy in patients with progressive disease harboring the T790M mutation and in the first-line setting, bypassing this mode of resistance. The primary objectives of this study are to describe the proportion of EGFRm+ NSCLC patients treated with first-, second- and third-generation EGFR TKIs, and cytotoxic chemotherapy in the first-line setting, and the time on treatment for each category. Secondary objectives are to determine the dropout rate, the rates for T790M mutation testing at disease progression and the type of subsequent treatment. Methods: This multicenter retrospective study utilized data from the Malaysian Lung Cancer Registry that actively registers all lung cancer patients ≥18 years, with primary lung cancer confirmed histologically or cytologically. All patients diagnosed with advanced stages (ie stages IIIB, IIIC and IV) EGFRm+ NSCLC from 1st of January 2015 to 31st December 2019 were included. Results: Of 406 patients with EGFRm+ NCSLC, 351 were treated. Types of first-line treatment were as follows: EGFR-TKIs (first generation - 54.1%, second generation - 25.6% and third-generation - 12.5%) and chemotherapy (7.7%). The median time of treatment for each generation of EGFR-TKI was 12 months, 12 months and 24 months, and 2 months for chemotherapy. The dropout rate was 28.7% (n = 101). Nearly half (49.4%) of patients who were on first- or second-generation EGFR-TKI had further genetic testing via liquid or tissue biopsies upon disease progression. About 24.9% of those who developed disease progression after first- or second-generation EGFR TKI were started on a third-generation EGFR TKI. Conclusion: In the real-world, the management of EGFRm+ advanced NSCLC patients in an Asian cost-restrictive setting may adversely affect the choice of first-line therapy, time on each line of treatment and subsequently the overall survival of patients.

Prevalence of glycemic variability and factors associated with the glycemic arrays among end-stage kidney disease patients on chronic hemodialysis.

ABSTRACT: Glycemic variability (GV) confers a significantly higher risk of diabetic-related complications, especially cardiovascular. Despite extensive research in this area, data on end-stage kidney disease (ESKD) patients on chronic hemodialysis are scarce. This study aims to determine the magnitude of GV among ESKD (diabetic vs nondiabetic) patients and its associated factors on hemodialysis days (HDD) and non-hemodialysis days (NHDD) where postulation of a higher GV observed among diabetic on HDD.We recruited 150 patients on hemodialysis, 93 patients with type 2 diabetic (DM-ESKD), and 57 with nondiabetic (NDM-ESKD). The GV indices (standard deviation [SD] and percentage coefficient variant [%CV]) were obtained from 11-point and 7-point self-monitoring blood glucose (fasting to post-meal) (SMBG) profiles on HDD and NHDD. The GV indices and its associated factors of both DM-ESKD and NDM-ESKD were analyzed to compare HDD vs NHDD.Mean blood glucose on HDD was 9.33 [SD 2.7, %CV 30.6%] mmol/L in DM-ESKD compared with 6.07 [SD 0.85, %CV 21.3%] mmol/L in NDM-ESKD (P = <.01). The DM-ESKD group experienced significantly above target GV indices compared to NDM-ESKD on both HDD and NHDD, particularly in the subgroup with HbA1c 8-10% (P = <.01). Presence of diabetes, older age, hyperlipidemia, HbA1c, ferritin levels, and albumin were identified as factors associated with GV.DM-ESKD patients have above-target GV indices, especially on HDD, therefore increasing their risk of developing future complications. We identified high HbA1c, older age group, presence of hyperlipidemia, ferritin levels, and albumin as factors associated with GV indices that may be used as surrogate markers for GV. Since these groups of patients are vulnerable to CVD mortality, urgent attention is needed to rectify it.