Survival Bias Research Articles

Is Fragmented Cancer Care Associated With Medical Expenditure? Nationwide Evidence From Patients With Lung Cancer Using National Insurance Claim Data.

Objectives: We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data. Methods: We identified National Health Insurance beneficiaries diagnosed with lung cancer in South Korea from 2010 to 2014. We included 1,364 lung cancer patients with reduced immortal time bias and heterogeneity. We performed multiple regression analysis using a generalized estimate equation with a gamma distribution for medical expenditures. Results: Among the 1,364 patients with lung cancer, 12.8% had fragmented cancer care. Healthcare costs were higher in fragmented cancer care for both during diagnosis to 365days and diagnosis to 1,825days. Linear regression results showed that fragmented cancer care was associated with 1.162 times higher costs during the period from diagnosis to 365days and 1.163 times the cost for the period from diagnosis to 1,825days. Conclusion: We found fragmented cancer care is associated with higher medical expenditure. Future health policy should consider the limitation of patients' free will when opting for fragmented cancer care, as there are currently no control mechanisms.

Immortal Time Bias With Time-Varying Exposures in Environmental Epidemiology: A Case Study in Lung Cancer Survival.

Immortal time bias is a well-recognized bias in clinical epidemiology but is rarely discussed in environmental epidemiology. Under the target trial framework, this bias is formally conceptualized as a misalignment between the start of study follow-up (time 0) and treatment assignment. This misalignment can occur when attained duration of follow-up is encoded into treatment assignment using minimums, maximums, or averages. The bias can be exacerbated in the presence of time trends commonly found in environmental exposures. Using lung cancer cases from the California Cancer Registry (2000-2010) linked with estimated concentrations of particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM2.5), we replicated previous studies that averaged PM2.5 exposure over follow-up in a time-to-event model. We compared this approach with one that ensures alignment between time 0 and treatment assignment, a discrete-time approach. In the former approach, the estimated overall hazard ratio for a 5-μg/m3 increase in PM2.5 was 1.38 (95% confidence interval: 1.36, 1.40). Under the discrete-time approach, the estimated pooled odds ratio was 0.99 (95% confidence interval: 0.98, 1.00). We conclude that the strong estimated effect in the former approach was likely driven by immortal time bias, due to misalignment at time 0. Our findings highlight the importance of appropriately conceptualizing a time-varying environmental exposure under the target trial framework to avoid introducing preventable systematic errors.

Adenocarcinoma of the Bladder: Assessment of Survival Advantage Associated With Radical Cystectomy and Comparison With Urothelial Bladder Cancer

To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC). Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T2N0M0) or non-organ-confined (NOC: T3-4N0M0 or TanyN1-3M0) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed. Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results. In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias.

Unread, yet preserved: A case study on survival of the 19th-century printed poetry

Distant reading promises access to "the great unread", which should allow scholars to rethink the history of literature. However, the rise in volume of data does not guarantee the understanding of a corpus and its relation to the literary population. This article discusses how a "complete" corpus of the 19th-century poetry books in Russian might be collected with account for historical data and potential survivorship bias. Even if bibliographical sources cannot provide a complete list of books printed in a given period, the amount of "incompleteness" can be directly estimated with the unseen species models. The estimation of survival ratios for printed poetry shows differences in the loss rate across different types of sources: with conventional editions, like books and anthologies, are well-preserved, while booklets and pamphlets are the largest expected source of loss. These findings allow us to estimate what an "exhaustive" corpus can look like and define the features of "the unread" and "unseen" inside it.

The Impact of COVID-19 on Parkinson’s Disease: A Case-Controlled Registry and Questionnaire Study on Clinical Markers and Patients’ Perceptions

Introduction. Parkinson’s disease (PD) is a neurodegenerative disease with motor and nonmotor symptoms. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives. To explore how COVID-19 affects motor, nonmotor, and general health aspects of PD and to map how PD patients perceive their change in symptoms since falling ill with COVID-19. Method. The study was descriptive, case-controlled, and based on both registry and questionnaire data. At baseline, the controls were matched on age, sex, and disease severity. Information on the severity of the disease, nonmotor symptoms, motor symptoms, and general health was retrieved from the Swedish Registry for PD. Registry data from a COVID-19 group ( n = 45 ) and a control group ( n = 73 ), as well as questionnaires from a COVID-19 group ( n = 24 ) and a control group ( n = 42 ), were compared. Results. We did not find that SARS-CoV-2 infection affects any major aspect of nonmotor symptoms, motor symptoms, general health, and perception of change in PD patients’ post-COVID-19. Compared to controls, the COVID-19 group reported a more positive subjective experience of pain and quality of life and a perception of change post-COVID-19 regarding general motor function, sleep quality, and mood (all p &lt; 0.05 ). Conclusion. Although SARS-CoV-2 infection does not seem to affect PD symptoms in any major respect, the subjective experience of several aspects of life in PD patients might be slightly improved post-COVID-19 compared to a control group. The findings warrant further investigations due to the small sample size and possible survivorship bias.

Effect of statins on the recurrence of hepatocellular carcinoma after liver transplantation: An illusion revealed by exposure density sampling.

Statins have been reported to reduce overall death and hepatocellular carcinoma (HCC) recurrence in liver transplantation (LT) recipients. However, previous retrospective studies have significant flaws in immortal time bias. Using data from 658 patients who received LT for HCC, we matched 140 statin users with statin nonusers in a 1:2 ratio at the time of the first statin administration after LT using the exposure density sampling (EDS). The propensity score, calculated using baseline variables (including explant pathology), was used for EDS to equilibrate both groups. HCC recurrence and overall death were compared after adjusting for information at the time of sampling. Among statin users, the median time to statin start was 219 (IQR 98-570) days, and intensity of statins was mainly moderate (87.1%). Statin users and nonusers sampled using EDS showed well-balanced baseline characteristics, including detailed tumour pathology, and similar HCC recurrence with cumulative incidences of 11.3% and 11.8% at 5 years, respectively (p = .861). In multivariate Cox models (HR 1.04, p = .918) and subgroup analyses, statins did not affect HCC recurrence. Conversely, statin users showed a significantly lower risk of overall death than nonusers (HR 0.28, p < .001). There was no difference in the type and intensity of statin usage between statin users who experienced HCC recurrence and those who did not. Upon controlling immortal time bias by EDS, statins did not affect HCC recurrence but reduced mortality after LT. Statin usage is encouraged for survival benefits but not for preventing HCC recurrence in LT recipients.

Is research on hedge fund performance published selectively? A quantitative survey

AbstractWe examine whether estimates of hedge fund performance reported in prior empirical research are affected by publication bias. Using a sample of 1019 intercept terms from regressions of hedge fund returns on risk factors (the “alphas”) collected from 74 studies published between 2001 and 2021, we show that the selective publication of empirical results does not significantly contaminate inferences about hedge fund returns. Most of our monthly alpha estimates adjusted for the (small) bias fall within a relatively narrow range of 30–40 basis points, indicating positive abnormal returns of hedge funds: Hedge funds generate money for investors. Studies that explicitly control for potential biases in the underlying data (e.g., backfilling and survivorship biases) report lower but still positive alphas. Our results demonstrate that despite the prevalence of publication selection bias in many other research settings, publication may not be selective when there is no strong a priori theoretical prediction about the sign of the estimated coefficients.

Lost in data translation: A critical review of datasets on refugees

AbstractQuantitative data are the backbone of the international refugee regime. Academic researchers and international organizations have been drawing attention to the problems of refugee data that obscure refugee vulnerabilities. Despite these efforts, the limitations of quantitative refugee data, particularly with regard to gendered aspects of refugee vulnerabilities, have often been overlooked. This article aims to address this issue by examining the major limitations of quantitative refugee data. It focuses on the question of “What are the major limitations of quantitative refugee data regarding gendered aspects of refugee vulnerabilities?” By conducting a systematic review of 67 datasets from international organizations, nation‐states, and independent data collectors, it argues that there are five fundamental problems with the data: (1) lack of disaggregation, (2) lack of cross‐tabulation and inability to harmonize datasets, (3) inconsistent periodization frequency, (4) lack of sex and gender diversity measurement, and (5) survivor bias. This article highlights the importance of critically analysing the data that informs theories and decisions regarding refugee vulnerabilities.

#5533 DOES AV FISTULA FORMATION DELAY TIMING OF INITIATION OF KIDNEY REPLACEMENT THERAPY IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE?

Abstract Background and Aims Several retrospective observational studies have supported kidney protective effects of arteriovenous fistula (AVF) formation. However, these studies were limited by immortal time and selection biases. We investigated whether AVF formation delays the initiation of kidney replacement therapy (KRT) in patients with stage 5 CKD by applying target trial emulation methods, which do not suffer from these biases. Method We included adult patients who had an eGFR ≤15 mL/min/1.73m2, attended the ‘low clearance’ nephrology clinic in the West of Scotland between January 1st 2010 and May 1st 2022, and had no prior AVF or AV graft formation. Available data were obtained from the Strathclyde Electronic Renal Patient Record. The target trial would randomize patients to either receive an AVF immediately or to not receive an AVF. To emulate this trial, we matched each patient who underwent AVF formation to patients who had not undergone AVF formation but remained eligible to participate in the trial, and were matched in sex, age (within 5 years) and eGFR (within 0.5 ml/min/1.73m2). Inverse probability of treatment weighting was used to adjust for baseline confounders, including age, sex, comorbidities, medication use, serum and urine biochemical measurements (eGFR CKD-EPI, eGFR CKD-EPI slope for 6 months preceding trial, haemoglobin, C-reactive protein, albumin, phosphate, adjusted calcium, ferritin, urine protein:creatinine ratio), and blood pressure. The primary outcome was kidney replacement therapy. The eGFR slope closest to the time of AVF creation was estimated as a co-primary endpoint. We estimated hazard ratios using Cox regression and estimated restricted mean survival time (RMST) from the Kaplan-Meier curves. The eGFR slope co-primary endpoint was analysed with a mixed-effects model. Results Among 2,988 included patients (55% men; mean [SD] age 64 [15] years), AVF formation was associated with a higher risk of KRT (HR 1.45; CI 1.20–1.49, p &amp;lt;0.001, Figure 1) and a lower risk of death (HR 0.68; (0.64–0.80, p = 0.001). The AVF group had a lower KRT-free survival with an estimated RMST difference of 265 days (95% CI −331 to −199, p &amp;lt;0.001) and higher overall survival (RMST difference of 191 days; 95% CI 57 to 326, p = 0.005). Finally, we used a mixed-effects model to analyse the association between eGFR CKD-EPI, time, and AVF formation. AVF formation and time were both associated with a negative slope in the model (estimates −1.28; 95% CI −1.36 to −1.19, p&amp;lt;0.001 and −0.01; 95% CI −0.01 to −0.01, p&amp;lt;0.001, respectively, Figure 2). Their interaction was also associated with a negative slope (estimate −0.001; 95% CI −0.0022 to −0.0004, p &amp;lt;0.001), suggesting those undergoing AVF formation had a more rapid eGFR decline compared to the control group. Conclusion Unlike what was observed in previously published work, we did not identify a kidney protective effect of AVF formation. The estimated time of dialysis initiation remains the main determinant for timing of access surgery. These findings illustrate the usefulness of target trial emulation in approaching research questions where randomised controlled trials would be impractical.

A retrospective multicentric cohort study of checkpoint inhibitors-induced pruritus with focus on management.

Limited data on immune checkpoint inhibitor (ICI)-induced pruritus per se and efficacy of different therapeutic modalities in its management exist. To study the quantitative and qualitative characteristics of ICI-induced pruritus per se and to assess the efficacy of the therapeutic modalities usually applied. We retrospectively reviewed the records of 91 patients who were under treatment with ICIs for any kind of neoplasia and developed pruritus during treatment. Twenty out of 91 individuals (22.0%) with ICI-induced pruritus had pruritus as the only symptom, while 71/91 (78.0%) presented with pruritus coexisting with an additional cutaneous toxicity. Pruritus was treated with antihistamines (18/20, 90.0%) and/or topical regimens, as first-line choice. In resistant cases, as a second therapeutic intervention, narrow-band UVB (NBUVB), oral steroids and GABA analogs were added (70.0%). Statistical analysis revealed a significant difference in mean pruritus Numerical Rating Scale (NRS) scores between baseline and sequential visits. Moreover, subgroup analysis revealed a significant reduction in mean NRS scores in those treated with phototherapy. Retrospective design, low number of patients and survivorship bias. Pruritus per se was present in a substantial portion of our cohort (22.0%). Our study confirms the efficacy of current treatment strategies and suggests NBUVB as a potential steroid-sparing therapeutic alternative.

Survival of de novo metastatic hormone sensitive prostate cancer in US Veterans based on treatment and PSA at diagnosis.

e17091 Background: Combinations of androgen deprivation therapy (ADT) plus docetaxel (DOC) or androgen signaling agents (ASIs) (i.e. abiraterone, enzalutamide) improve survival in de novo metastatic hormone sensitive prostate cancer (mHSPC). In several trials, the benefit of combination therapy is greatest in patients with a high volume of disease. We sought to study the treatment and survival of US of veterans with mHSPC and stratify by PSA level at diagnosis during a time when different types of combination therapy was available. Methods: Veterans from 2018-2021 were identified with a pathologic diagnosis of prostate cancer with SEER stage ‘distant’. All veterans had ADT initiated within 1 month prior and 4 months after diagnosis. Combination therapy was determined if DOC or an ASI was initiated from 1 month prior to 4 months after ADT. Highest PSA level within 3 months of diagnosis was collected and patients with a PSA of ≥100ng/mL were included in PSA≥100. To avoid immortal time bias, all veterans had to survive 4 months after biopsy to be included. Baseline differences were compared using ANOVA and log-rank testing was used for time to event analyses. Results: 2,227 patients with de novo mHSPC were identified with mean age of 74.0 years (yrs), and 575 (25.8%) identified as Black race. From 2018 to 2021, ADT alone was used in 1,157 (52.0%) of veterans, DOC in 189 (8.4%) and ASIs in 881 (39.6%). Veterans treated with DOC were significantly younger (median 67.7 yrs, p &lt; 0.001) compared to veterans treated with ASIs (72.9 yrs) or ADT alone (75.8 yrs). Veterans treated with combination therapies had longer median OS of 40.9 months (mos) compared to 32.9 mos for ADT alone (p &lt; 0.001) with no difference within the combination treatment groups (p = 0.63). There was a trend for veterans with PSA≥100 to receive combination therapy (50.0% vs. 46.0%, p = 0.058). For 1,071 veterans with PSA≥100, median OS of veterans treated with combination therapy (n = 536, 37.4 mos) was longer than ADT alone (n = 535, 27.5 mos, p &lt; 0.001). There was no differences in DOC combination treatment (n = 100, 37.9 mos) and ASI (n = 436, 36.6 mos) treatment groups (p = 0.37). Veterans with PSA≥100 had shorter OS compared to PSA &lt; 100 (31.2 vs. 42.5 mos, p &lt; 0.001). Conclusions: In veterans with de novo mHSPC, initial combination therapy was associated with longer survival than ADT alone. There were no differences in survival between DOC and ASI combinations observed in the entire population nor in veterans with PSA≥100. Further studies including tumor genetics or response to treatment may help guide treatment in mHSPC. [Table: see text]

Do corticosteroids affect immunotherapy efficacy in malignancy? A systematic review.

e14692 Background: Early studies indicate that corticosteroids may limit survival benefits from immunotherapy, although this finding is potentially confounded by the poor prognosis of patients who require corticosteroids due to cancer-related symptoms. We conducted this systematic review to evaluate the effect corticosteroids have on immunotherapy, when adjusted for potentially confounding effects of corticosteroids given for palliative indications. Methods: 3 databases (PubMed, Embase, and Medline) were searched on 1st of February 2023. Studies that measured response or survival in patients receiving immunotherapy, while receiving corticosteroids for non-cancer indications, compared to either no corticosteroids or corticosteroids for cancer-related indications were included. Studies exclusively evaluating the effect of corticosteroids administered for immune-related adverse events were excluded to avoid immortal time bias. Pooled odds and hazard ratios with 95% confidence intervals (CI) were calculated using a random effects model. Study heterogeneity was assessed using the I2 statistic, and publication bias was evaluated by funnel plot and Egger's regression model. Results: 8,426 studies were identified, of which 8 studies met our inclusion criteria for meta-analysis. Administration of steroids has no statistically significant effect on survival and response to immunotherapy when administered for non-cancer related indications, with a pooled odds ratio for overall response rate 0.92 (95% CI 0.58-1.44); pooled hazard ratio (HR) for progression free survival 0.87 (95% CI 0.68-1.12); and pooled HR for overall survival 0.79 (95% CI 0.59-1.05). Conclusions: This systematic review indicates that administration of corticosteroids does not affect response to immunotherapy nor survival outcomes, when removing confounding palliative corticosteroid indications. Limiting or minimising corticosteroid treatment in this patient population due to concern of potential lowered efficacy of immunotherapy can therefore be reconsidered. These results are limited by the retrospective nature of the studies, small sample sizes, and the lack of information about corticosteroid dosing or length of treatment.

Racial/ethnic differences in 21-gene recurrence score and survival among estrogen receptor-positive breast cancer patients.

511 Background: Despite studies on racial/ethnic disparities in breast cancer patients, there is limited literature evaluating association of racial/ethnic differences with 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We performed an observational cohort study to evaluate such disparities in context of RS. Methods: The National Cancer Database (NCDB) was queried for patients with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with available RS from 2006 to 2018. Racial/ethnic groups were stratified by non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API). Our primary endpoint was overall survival (OS). Logistic multivariable analysis (MVA) was built upon baseline patient and tumor characteristics to evaluate variables associated with RS &gt; 25. Cox MVA was used to evaluate OS. Interaction term analysis was used to identify heterogeneous association of racial/ethnic groups and RS; if significant, subgroup analyses compared magnitude of racial/ethnic differences stratified by RS. To address immortal time bias, Cox MVA analyses were repeated after excluding patients with post-diagnosis survival &lt; 6 months. P values were two-sided. Bonferroni correction was used for multiple comparisons (NHW vs HW women, NHW vs Black women, and NHW vs API women) with p values less than 0.017 being statistically significant. Results: A total of 140,133 women (median [interquartile range (IQR)] age, 60 [52-67] years) were included for analysis. 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women respectively. Median (IQR) follow up was 66.2 mo. (48.0-89.8). Logistic MVA showed compared to NHW women, Black women were associated with higher RS (26 or higher vs &lt; 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.26, p &lt; 0.001), while HW (aOR 0.93, 95% CI 0.86-1.00, p = 0.04) and API (aOR 1.03, 95% CI 0.95-1.13, p = 0.45) were not. Cox MVA showed compared to NHW, Black women were associated with worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02-1.19, p = 0.012) while HW (aHR 0.85, 95% CI 0.77-0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56-0.77, p &lt; 0.001) were not. There was significant interaction between race/ethnicity and RS (interaction p = 0.006). Subgroup analysis found similarities in those with RS &lt; 26, while only API women were associated with improved OS among those with RS ≥ 26. After excluding those with post-diagnosis survival &lt; 6 mo., our findings remained comparable. Conclusions: To our knowledge, this is the largest nationwide oncology database study to suggest that Black women are associated with higher RS, while HW and API are not. It also suggests that Black women are associated with worse OS among those with RS &lt; 26, while API are associated with improved OS regardless of RS compared to NHW women.

Renal cell carcinoma with metastasis to the pancreas: Genomic signatures and clinical outcomes.

e16519 Background: Renal cell carcinoma (RCC) is a diverse disease characterized by several subtypes, mutations, and a broad spectrum of sites of metastasis. Previous publications have established that RCC with pancreatic metastases (PM), a rare subpopulation, has more favorable outcomes, even when other metastases sites are involved. Outcomes in this subpopulation tend to be independent of the traditional IMDC risk stratification. We have previously explored the genomic landscape of RCC with PM. In this analysis, we explore the clinical data and correlation with NGS for a subset of patients treated at our institution. Methods: We identified patients (pts) at our institution with metastatic RCC with PM. Included pts had pathologically confirmed RCC with met to pancreas seen on imaging. All identified pts had NGS performed with Tempus xT assay (DNA-seq of 648 genes at 500x coverage). We also extracted demographic, clinicopathologic, and treatment data for included pts through chart review. We describe baseline characteristics, most prevalent gene mutations on xT and overall survival (OS) from time of diagnosis to death with particular attention of OS stratified by PBRM1 mutation. We also performed a log rank test to compare OS for those with and without PBRM1 mutation. Results: 23 pts with metastatic RCC with PM were identified. Pts included were diagnosed with RCC between 1993 and 2020, median age was 62 years (range 42-78), 48% were female, 70% of white race, 35% with smoking history. All patients had a nephrectomy and 91% had clear cell histology. 6 pts (26%) had de novo metastatic disease (3 [14%] with de novo PM). Median time to metastatic disease was 3.5 years (range 0-15.5 years) and median time to PM was 4.7 years (range 0-15.5 years). The most prevalent genes identified with mutations were VHL (70%), PBRM1 (39%), and SETD2 (32%); TP53 mutations were identified in 2 pts (9%). After a median follow-up of 16 years, 10 pts (43%) were deceased (7 due to RCC, 3 due to other causes), 11 pts were alive (5 without disease and 6 with active disease) and 2 with unknown vital status. Median [m]OS for the whole cohort was 12.7 years, which when stratified by PBRM1 mutation was 8.4 and 12.7 years for those with and without PBRM1 mutation, respectively, though this difference was not statistically significant. Conclusions: In our cohort, patients with RCC and PM had an indolent course with a prolonged survival even after diagnosis of metastatic disease. This effect was independent of PBRM1 mutations or other common mutations. As these patients presented with both de novo PM as well as later in the course, this may represent a unique population, rather than a result of survival bias.

Competing risks analysis of external versus internal radiation in patients with hepatocellular carcinoma after controlling for immortal time bias.

In cohort studies on liver cancer, there are often immortal time bias and interference of competing risk events. This study proposes to explore the role of internal and external radiotherapy for hepatocellular carcinoma using SEER data, using a competing risk model and controlling immortal time bias. Data of SEER from 2004 till 2015 was included. To analyze whether there was a difference in survival between HCC (hepatocellular carcinoma) patients receiving external radiation and internal radiation, we used a competing risk analysis after excluding immortal time bias, and created a nomogram to assess the risk of cancer-specific death (CSD) in hepatocellular carcinoma patients receiving radiotherapy. Potential confounding factors adjusted, there was no significant difference in CSD between external and internal radiation therapy [HR and its 95% CI = 1.098 (0.874-1.380)]. The constructed nomogram performed better than the traditional AJCC model. The AUC and calibration curve results showed that this well-calibrated nomogram could be used to make clinical decisions regarding the prognosis and personalized treatment of hepatocellular carcinoma treated. There was no difference in the cumulative risk of death between patients with liver cancer treated with external radiation therapy and internal radiation therapy. There is no difference in the cumulative risk of death between patients with liver cancer treated with external radiation therapy and internal radiation therapy. The nomogram predicts the results more accurately. These results can be used to guide the choice of treatment options for patients with HCC and to predict their survival prognosis.

Polygenic scores for estimated glomerular filtration rate in a population of general adults and elderly – comparative results from the KORA and AugUR study

BackgroundPolygenic scores (PGSs) combining genetic variants found to be associated with creatinine-based estimated glomerular filtration rate (eGFRcrea) have been applied in various study populations with different age ranges. This has shown that PGS explain less eGFRcrea variance in the elderly. Our aim was to understand how differences in eGFR variance and the percentage explained by PGS varies between population of general adults and elderly.ResultsWe derived a PGS for cystatin-based eGFR (eGFRcys) from published genome-wide association studies. We used the 634 variants known for eGFRcrea and the 204 variants identified for eGFRcys to calculate the PGS in two comparable studies capturing a general adult and an elderly population, KORA S4 (n = 2,900; age 24–69 years) and AugUR (n = 2,272, age ≥ 70 years). To identify potential factors determining age-dependent differences on the PGS-explained variance, we evaluated the PGS variance, the eGFR variance, and the beta estimates of PGS association on eGFR. Specifically, we compared frequencies of eGFR-lowering alleles between general adult and elderly individuals and analyzed the influence of comorbidities and medication intake. The PGS for eGFRcrea explained almost twice as much (R2 = 9.6%) of age-/sex adjusted eGFR variance in the general adults compared to the elderly (4.6%). This difference was less pronounced for the PGS for eGFRcys (4.7% or 3.6%, respectively). The beta-estimate of the PGS on eGFRcrea was higher in the general adults compared to the elderly, but similar for the PGS on eGFRcys. The eGFR variance in the elderly was reduced by accounting for comorbidities and medication intake, but this did not explain the difference in R2-values. Allele frequencies between general adult and elderly individuals showed no significant differences except for one variant near APOE (rs429358). We found no enrichment of eGFR-protective alleles in the elderly compared to general adults.ConclusionsWe concluded that the difference in explained variance by PGS was due to the higher age- and sex-adjusted eGFR variance in the elderly and, for eGFRcrea, also by a lower PGS association beta-estimate. Our results provide little evidence for survival or selection bias.

Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma: An Updated Nationwide Study.

The objective of this study was to assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates, and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. In total, 4041 patients were treated with upfront surgery and 1,175 patients were treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival compared with upfront surgery and single-agent NAC. (35.8 vs 27.1 vs 27.4mo). Multiagent NAC was associated with lower mortality rates compared with upfront surgery (adjusted hazard ratio, 0.77; 95% CI, 0.70-0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that the association between multiagent NAC and a lower mortality rate did not significantly differ across age, facility type, tumor location, CA 19-9 levels, and clinical T/N stages. The findings suggest that multiagent NAC followed by resection is associated with improved survival compared with upfront surgery.

Immortal Time Bias: the hidden confounder in assessing cardiosurgical treatment effects.

(A) Schematic illustration of the principle of immortal time bias. The grey mortality curve illustrates an assumption of mortality risk in patients with infective endocarditis while waiting for surgery based on data from four studies reporting on the survival of patients with infective endocarditis who had a surgical indication but did not receive surgery.1–4 The columns schematically reflect an assumption of mortality risk associated with waiting for (brown columns) and with receiving surgery (blue columns) at a given time (early or late surgery), as an example. The vertical red line then represents the difference in mortality associated with waiting for surgery, which reflects the ‘immortal time bias’ in this example, if a retrospective assessment of surgical mortality is performed. (B) Postoperative mortality (left panel) and postoperative neurological deterioration (right panel) associated with surgery or conservative treatment, depending on the time of surgery. Data were obtained from a meta-analysis involving nine studies on infective endocarditis with intracranial haemorrhage.5 The times on the x-axis reflect the cut-off for surgery performed before or after this time.

Through the labyrinth: women in the public universities of Pakistan

The purpose of this study is to find out how women negotiate their path to leadership; the barriers and facilitators and how they navigated them to reach the top. An inductive, qualitative approach has been used to systematically analyze the in-depth open-ended responses of female leaders in public higher education institutions and note emergent themes. Women face various endogenous and exogenous challenges in their journey to the top. The major emergent themes turned out to be personal cognizance, individual development, breaking gender stereotypes, and embracing and translating gynandrous leadership by women leaders. Familial support and women-friendly organizational policies were regarded as the most significant enablers. The major barriers turned out to be a lack of institutional support and grit among women. The metaphor of the labyrinth turned out to be an apt metaphor for studying the journeys of women. This research is limited by survivor bias as it only studies women who successfully navigated the labyrinth to the top but not those who got lost in the labyrinth. This study examines the leadership journeys of women leaders in public higher education in Pakistan by extending the metaphor of a labyrinth in the public sector in academia. It also proposes a conceptual model of how women navigate the labyrinth.

Letter to the Editor: Is there survival bias? The etiologic analysis for the negative association between fatty liver and mortality in the elderly populations.

Letter to the Editor: Is there survival bias? The etiologic analysis for the negative association between fatty liver and mortality in the elderly populations.