Evaluating Methods for Dealing with Missing Outcomes in Discrete-Time Event History Analysis: A Simulation Study

Background: In discrete-time event history analysis, subjects are measured once each time period until they experience the event, prematurely drop out, or when the study concludes. This implies measuring event status of a subject in each time period determines whether (s)he should be measured in subsequent time periods. For that reason, intermittent missing event status causes a problem because, unlike other repeated measurement designs, it does not make sense to simply ignore the corresponding missing event status from the analysis (as long as the dropout is ignorable). Method: We used Monte Carlo simulation to evaluate and compare various alternatives, including event occurrence recall, event (non-)occurrence, case deletion, period deletion, and single and multiple imputation methods, to deal with missing event status. Moreover, we showed the methods’ performance in the analysis of an empirical example on relapse to drug use. Result: The strategies assuming event (non-)occurrence and the recall strategy had the worst performance because of a substantial parameter bias and a sharp decrease in coverage rate. Deletion methods suffered from either loss of power or undercoverage issues resulting from a biased standard error. Single imputation recovered the bias issue but showed an undercoverage estimate. Multiple imputations performed reasonably with a negligible standard error bias leading to a gradual decrease in power. Conclusion: On the basis of the simulation results and real example, we provide practical guidance to researches in terms of the best ways to deal with missing event history data.

Real-world clinical effectiveness of sorafenib among patients with unresectable hepatocellular carcinoma at two centers in the United States

BACKGROUND In the United States,sorafenib monotherapy was approved in 2007 for first-line(1L)treatment of patients with unresectable hepatocellular carcinoma(uHCC).As other therapies have been approved in recent years for hepatocellular carcinoma treatment in later lines,it is essential to assess clinical effectiveness of older therapies in actual clinical practice to inform healthcare practitioners’decisions for better patient care.AIM To assess patient characteristics/clinical effectiveness of 1L sorafenib in uHCC patients treated in United States academic and community practice settings.METHODS A retrospective observational study was conducted among adult patients(≥18 years)in the United States initiating sorafenib monotherapy as 1L systemic therapy for uHCC with Eastern Cooperative Oncology Group status of 0 or 1 between January 2016 and December 2019 at City of Hope and Advent Health.Data were extracted by trained abstractionists from individual patients’electronic health records and captured in electronic case report forms.Institutional Review Board approvals were obtained prior to study initiation.Data were captured from the time of sorafenib initiation until death or the end of follow-up.All data were de-identified prior to analyses.Clinical outcomes assessed included provider-reported best response,progression-free survival(PFS),and overall survival(OS).PFS and OS were estimated using Kaplan-Meier methods.RESULTS Among 134 uHCC patients treated with 1L sorafenib,majority were male(75%),and most were Caucasian(62%)or Asian(19%).Median patient age was 64 years.The most common etiologies of liver disease were hepatitis C(54%),alcohol-related liver disease(16%),and hepatitis B(11%).Most patients were reported to have Barcelona Clinic Liver Cancer stage B(19%)or stage C(70%)disease.Of 134 patients,110(82%)were reported to have discontinued treatment or died during follow-up.Primary reasons for sorafenib discontinuation were reported as progression(35%)and toxicity(30%).Best overall response was reported for 124 patients,of which 7.3%reported complete or partial response.Median time to treatment discontinuation was 2.3 mo.Overall,103 patients(77%)had disease progression or died during sorafenib therapy.Median PFS was estimated to be 2.9 mo.At the end of follow-up,82 patients(61%)were deceased.Median OS was 8.5 mo.CONCLUSION Newer therapeutic options that have reported higher PFS and OS in real-world clinical practice should be considered to enhance patient outcomes.

Outcomes in patients with COVID-19 and new onset heart blocks: Insight from the National Inpatient Sample database

BACKGROUND Coronavirus disease 2019(COVID-19)caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has resulted in a worldwide health crisis since it first appeared.Numerous studies demonstrated the virus’s predilection to cardiomyocytes;however,the effects that COVID-19 has on the cardiac conduc-tion system still need to be fully understood.AIM To analyze the impact that COVID-19 has on the odds of major cardiovascular complications in patients with new onset heart blocks or bundle branch blocks(BBB).METHODS The 2020 National Inpatient Sample(NIS)database was used to identify patients admitted for COVID-19 pneumonia with and without high-degree atrioven-tricular blocks(HDAVB)and right or left BBB utilizing ICD-10 codes.The patients with pre-existing pacemakers,suggestive of a prior diagnosis of HDAVB or BBB,were excluded from the study.The primary outcome was inpatient mortality.Secondary outcomes included total hospital charges(THC),the length of hospital stay(LOS),and other major cardiac outcomes detailed in the Results section.Univariate and multivariate regression analyses were used to adjust for confounders with Stata version 17.RESULTS A total of 1058815 COVID-19 hospitalizations were identified within the 2020 NIS database,of which 3210(0.4%)and 17365(1.6%)patients were newly diagnosed with HDAVB and BBB,respectively.We observed a significantly higher odds of in-hospital mortality,cardiac arrest,cardiogenic shock,sepsis,arrythmias,and acute kidney injury in the COVID-19 and HDAVB group.There was no statistically significant difference in the odds of cerebral infarction or pulmonary embolism.Encounters with COVID-19 pneumonia and newly diagnosed BBB had a higher odds of arrythmias,acute kidney injury,sepsis,need for mechanical ventilation,and cardiogenic shock than those without BBB.However,unlike HDAVB,COVID-19 pneumonia and BBB had no significant impact on mortality compared to patients without BBB.CONCLUSION In conclusion,there is a significantly higher odds of inpatient mortality,cardiac arrest,cardiogenic shock,sepsis,acute kidney injury,supraventricular tachycardia,ventricular tachycardia,THC,and LOS in patients with COVID-19 pneumonia and HDAVB as compared to patients without HDAVB.Likewise,patients with COVID-19 pneumonia in the BBB group similarly have a higher odds of supraventricular tachycardia,atrial fibrillation,atrial flutter,ventricular tachycardia,acute kidney injury,sepsis,need for mechanical ventilation,and cardiogenic shock as compared to those without BBB.Therefore,it is essential for healthcare providers to be aware of the possible worse predicted outcomes that patients with new-onset HDAVB or BBB may experience following SARS-CoV-2 infection.

Revaluation of Helicobacter pylori's role in esophageal carcinoma: A call for comprehensive research

The study by López-Gómez et al,reports a significantly low prevalence(4.5%)of Helicobacter pylori(H.pylori)infection in esophageal cancer patients,contrasting sharply with the general population's infection rate.This finding challenges the established negative association between H.pylori and gastric malignancies,suggesting a potential protective role of H.pylori against esophageal carcinoma,particularly in the context of widespread proton pump inhibitor use.However,the study’s retrospective nature,single-center design,and small sample size limit the generalizability of the findings and raise concerns about selection bias and statistical power.Diagnostic methods primarily based on histology may not detect all cases,especially those with prior antibiotic or proton pump inhibitor use.Additionally,the study does not account for various confounding factors such as dietary habits,socio-economic status,and genetic predispositions that could affect the association between H.pylori and esophageal carcinoma.Further research with larger,more diverse cohorts and comprehensive data collection is necessary to clarify the complex relationship between H.pylori and esophageal carcinoma and substantiate these preliminary findings.