Survival and mortality of preterm neonates in a neonatal intensive care unit in Northern Ethiopia: a retrospective cohort study

The purpose of this study was to assess the predictors of preterm neonatal survival in a neonatal intensive care unit (NICU). A cohort study was conducted retrospectively on 1017 preterm neonates using medical records from January 2014 through December 2018. The Kaplan–Meier model was used to estimate mean survival time and cumulative survival probability. Furthermore, Multivariable Cox regression analysis was run to identify predictors of preterm neonatal mortality using an adjusted hazard ratio (AHR) at P < 0.05 and 95% confidence interval (CI). During the follow-up period in the NICU, the mean survival time of the preterm neonates was 47 (95% CI (43.19–48.95)) days. Compound presentation (AHR = 2.29, 95% CI (1.23–4.24)), perinatal asphyxia (AHR = 2.83, 95% CI (1.75–4.58)), respiratory distress syndrome (AHR = 3.01, 95% CI (1.80–5.01)), 1-min APGAR score (AHR = 0.78, 95% CI (0.62–0.98)), and birth weight (AHR = 0.32, 95% CI (0.17–0.58)) were found to be significant predictors of time to preterm neonatal mortality. In conclusion, the survival probability of preterm neonates showed a considerable decrement in the first week of life. Fetal presentation, gestational age, birth weight, 1-min APGAR score, perinatal asphyxia and respiratory distress syndrome found as independent predictors of preterm neonatal mortality.

Waiting Time for Second Kidney Transplantation and Mortality

Background and objectivesThe median kidney transplant half-life is 10–15 years. Because of the scarcity of donor organs and immunologic sensitization of candidates for retransplantation, there is a need for quantitative information on if and when a second transplantation is no longer associated with a lower risk of mortality compared with waitlisted patients treated by dialysis. Therefore, we investigated the association of time on waiting list with patient survival in patients who received a second transplantation versus remaining on the waiting list.Design, setting, participants, & measurementsIn this retrospective study using target trial emulation, we analyzed data of 2346 patients from the Austrian Dialysis and Transplant Registry and Eurotransplant with a failed first graft, aged over 18 years, and waitlisted for a second kidney transplantation in Austria during the years 1980–2019. The differences in restricted mean survival time and hazard ratios for all-cause mortality comparing the treatment strategies “retransplant” versus “remain waitlisted with maintenance dialysis” are reported for different waiting times after first graft loss.ResultsSecond kidney transplantation showed a longer restricted mean survival time at 10 years of follow-up compared with remaining on the waiting list (5.8 life months gained; 95% confidence interval, 0.9 to 11.1). This survival difference was diminished in patients with longer waiting time after loss of the first allograft; restricted mean survival time differences at 10 years were 8.0 (95% confidence interval, 1.9 to 14.0) and 0.1 life months gained (95% confidence interval, −14.3 to 15.2) for patients with waiting time for retransplantation of <1 and 8 years, respectively.ConclusionsSecond kidney transplant is associated with patient survival compared with remaining waitlisted and treatment by dialysis, but the survival difference diminishes with longer waiting time.

Efficacy of First-Third generation EGFR inhibitor combined with chemotherapy as first-line treatment for advanced lung adenocarcinoma in a real-world setting

BackgroundTo explore the optimal treatment strategy for patients who harbor sensitive EGFR mutations, a head-to-head study was performed to compare chemotherapy and gefitinib-erlotinip, osimertinib treatment in combination or with either agent alone as first-line therapy, in terms of efficacy and safety.MethodsA total of 200 untreated patients with advanced lung adenocarcinoma who harbored sensitive EGFR mutations were randomly assigned to receive gefitinib-erlotinip combined with pemetrexed and carboplatin group, gefitinib-erlotinip osimertinib combined with pemetrexed and carboplatin group, pemetrexed plus carboplatin alone group, or gefitinib-erlotinip alone group, osimertinib alone group.ResultsThe progression-free survival (PFS) of patients in the gefitinib-erlotinip combination group Mean Survival Time PFS 22.00 month,95%CI[16.29,27.70] and osimertinib gefitinib-erlotinip combination group Mean Survival Time PFS 40.00 month,95%CI[28.12,51.87]was longer than that of patients in the chemotherapy alone group PFS10,81 months, 95% CI,[ 8.99–12.64],gefitinib-erlotinip alone group PFS14.00 month.95%CI[11.98-20.01], osimertinib alone group PFS 26.66 month 95%CI[24.77-29.22].The gefitinib-erlotinip osimertinib combinational resulted in longer overall survival (OS) than chemotherapy alone (HR = 0.46, p = 0.016) or gefitinib-erlotinip alone (HR = 0.36, p = 0.01). osimertinib alone (HR = 0.26, p = 0.01).ConclusionsOur finding suggested that treatment with pemetrexed plus carboplatin combined with gefitinib-erlotinip and pemetrexed plus carboplatin combined with gefitinib-erlotinip osimertinib group could provide better survival benefits for patients with lung adenocarcinoma harboring sensitive EGFR mutations.

OP236 Evidence Synthesis Of Time-To-Event Outcomes In The Presence Of Non-Proportional Hazards

IntroductionSynthesis of clinical effectiveness is a well-established component of health technology assessment (HTA) combining data from multiple trials to obtain an overall pooled estimate of clinical effectiveness, which may inform an associated economic evaluation. Time-to-event outcomes are often synthesized using effect measures from Cox proportional hazards models assuming a constant hazard ratio over time. However, where treatment effects vary over time an assumption of proportional hazards is not always valid. Several methods have been proposed for synthesizing time-to-event outcomes in the presence of non-proportional hazards. However, guidance on choosing between these methods and the implications for HTA is lacking.MethodsWe applied five methods for estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption to a network of melanoma trials, reporting overall survival: restricted mean survival time, an accelerated failure time generalized gamma model, piecewise exponential, fractional polynomial and Royston-Parmar models. We conducted a simulation study to compare these five methods. Simulated individual patient data was generated from a mixture Weibull distribution assuming a treatment-time interaction. Each simulated meta-analysis consisted of five trials with varying numbers of patients and length of follow-up across trials. For each model fitted to each dataset, we calculated the restricted mean survival time at the end of observed follow-up and following extrapolation to a 20-year time horizon.ResultsAll models fitted the melanoma data reasonably well with some variation in the treatment rankings and differences in the survival curves. The simulation study demonstrated the potential for different conclusions from different modelling approaches.ConclusionsThe restricted mean survival time, generalized gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can all accommodate non-proportional hazards and differing lengths of trial follow-up within an evidence synthesis of time-to-event outcomes. Further work is needed in this area to extend the simulation study to the network meta-analysis setting and provide guidance on the key considerations for informing model choice for the purposes of HTA.

Novel Dual Acting Antimalarial Antileishmanial Agents Derived from Pyrazole Moiety

Malaria and leishmaniasis are two highly detrimental parasitic diseases with a global impact. Attempts to eradicate malaria and control leishmaniasis are generally unsuccessful due to the rapidly developing resistance to currently used drug therapy. The pyrazole ring is a key moiety reported to have a variety of biological activities. The current study aimed to design, synthesize and evaluate an array of pyrazole derivatives for potential antimalarial antileishmanial activity. The scheme for the synthesis of the pyrazole derivatives is presented. The antimalarial activity was assessed in-vivo on P. berghei ANKA infected mice to determine % parasitemia and mean survival time. The antileishmanial activity was assessed in-vitro, and IC50 for each compound was calculated. In-vivo acute toxicity and molecular docking on putative antimalarial and antileishmanial drug targets were performed using the most active compounds. All the derivatives exhibited significant antimalarial activity, the highest being 95% suppression of parasitemia with compounds 9a and 9b. The mean survival time of mice treated with these two compounds was also the highest (16-17 days) but was lower than chloroquine, the standard agent. Compounds 9a and 9b exhibited superior antileishmanial activity as compared to miltefosine. However, they were less potent than amphotericin. The compounds were safe and well-tolerated at toxic, oral and intraperitoneal, doses of 150mg/kg and 75mg/kg, respectively. Molecular docking of compound 9a revealed a good fitting pose with plasmodial Pf-DHFR enzyme and Lm-PTR1 enzyme, which explains the biological activity noted with this compound. Pyrazole derivatives 9a and 9b exhibited substantial dual antimalarial antileishmanial activity and may be a valuable scaffold for the design of further derivatives with antiprotozoal potential.

Thyroid disease and hepatocellular carcinoma survival. A Danish nationwide cohort study

Introduction Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000-2018. Patients’ age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goitre, and myxoedema, were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI 0.47-0.96) for thyrotoxicosis and 0.60 (95% CI 0.41-0.88) for nontoxic goitre. The restricted mean survival time during the five years following HCC diagnosis was 6.8 months (95% CI 1.1–12.6) longer for HCC patients with thyrotoxicosis than for patients without thyroid disease, and it was 6.9 months (95% CI 0.9–12.9) longer for HCC patients with nontoxic goitre than for patients without thyroid disease. Conclusions In this large nationwide cohort study, thyrotoxicosis and nontoxic goitre were associated with prolonged HCC survival.

Communicating About Mortality in Health Decision Support: ‘What and Why and When, and How and Where and Who’

The Covid-19 pandemic has only accelerated the need and desire to deal more openly with mortality, because the effect on survival is central to the comprehensive assessment of harms and benefits needed to meet a ‘reasonable patient’ legal standard. Taking the view that this requirement is best met through a multi-criterial decision support tool, we offer our preferred answers to the questions of What should be communicated about mortality in the tool, and How, given preferred answers to Who for, Who by, Why, When, and Where. Summary measures, including unrestricted Life Expectancy and Restricted Mean Survival Time are found to be reductionist and relative, and not as easy to understand and communicate as often asserted. Full lifetime absolute survival curves should be presented, even if they cannot be ‘evidence-based’ beyond trial follow-up limits, along with equivalent measures for other criteria in the (necessarily) multi-criterial decision. A decision support tool should relieve the reasonable person of the resulting calculation burden.