Survival analysis refers to statistical techniques which have been designed to circumvent the issues arising out of incomplete information regarding the time until which a desired event or endpoint ...occurs. The reasons for this may be manifold, for example, lost to follow-up, dropouts from the study, lack of sufficient research budget, and short follow-up period. It is one of the common but complicated analysis done in trials. The current article provides a step-wise guide toward understanding survival functions and performing it.
When applying secondary analysis on published survival data, it is critical to obtain each patient's raw data, because the individual patient data (IPD) approach has been considered as the gold ...standard of data analysis. However, researchers often lack access to IPD. We aim to propose a straightforward and robust approach to obtain IPD from published survival curves with a user-friendly software platform.
Improving upon existing methods, we propose an easy-to-use, two-stage approach to reconstruct IPD from published Kaplan-Meier (K-M) curves. Stage 1 extracts raw data coordinates and Stage 2 reconstructs IPD using the proposed method. To facilitate the use of the proposed method, we developed the R package IPDfromKM and an accompanying web-based Shiny application. Both the R package and Shiny application have an "all-in-one" feature such that users can use them to extract raw data coordinates from published K-M curves, reconstruct IPD from the extracted data coordinates, visualize the reconstructed IPD, assess the accuracy of the reconstruction, and perform secondary analysis on the basis of the reconstructed IPD. We illustrate the use of the R package and the Shiny application with K-M curves from published studies. Extensive simulations and real-world data applications demonstrate that the proposed method has high accuracy and great reliability in estimating the number of events, number of patients at risk, survival probabilities, median survival times, and hazard ratios.
IPDfromKM has great flexibility and accuracy to reconstruct IPD from published K-M curves with different shapes. We believe that the R package and the Shiny application will greatly facilitate the potential use of quality IPD and advance the use of secondary data to facilitate informed decision making in medical research.
Many imperiled species face increasing extinction risk that requires interventional management like translocation or captive rearing. The use of translocations to successfully restore or create ...populations requires that animals survive at recipient sites, information that is often lacking for imperiled species and that can be risky to acquire if not obtained before a species has dwindled in number. The giant gartersnake (Thamnophis gigas), a semiaquatic snake endemic to the Central Valley in California, USA, has declined after losing >90% of its historical habitat and may benefit from successful translocations to protected habitat. We released adult and captive‐reared juvenile snakes from 2 donor sites into a recently restored wetland in 2019 and 2020 and compared their survival, movement, and activity using radio‐telemetry through 2021. We monitored juvenile survival for 2 years in captivity after birth and then estimated post‐release survival at the recipient site using radio‐telemetry. Just 8% of translocated adult snakes survived >801 days (95% CI = 1–64%) compared with 39% of resident snakes at the donor sites surviving >1,154 days (95% CI = 23–68%). This equated to annualized survival rates of translocated adults (x¯ $\bar{x}$ = 0.32, 95% CI = 0.12–0.82) that were roughly half that of resident snakes (x¯ $\bar{x}$ = 0.74, 95% CI = 0.63–0.89). Translocation was negatively correlated with survival, but movement and activity received little support in models. Seventy‐six percent of juvenile snakes survived captivity and, once released, juvenile survival was 60% (95% CI = 38–94%) for the 4‐month monitoring period before winter. It is unclear why survival of translocated adult snakes was lower than that of resident snakes, but there was little evidence for differences in behavior (e.g., increased surface activity, average distance moved, emigration from the translocation site) that are commonly cited causes of mortality in other translocation studies. Our results suggest that, in the absence of a clear understanding as to what contributes to adult survival after release to a new site, future work using captive‐rearing and juvenile translocation may be more promising for establishing and recovering populations than just translocating adults given the high survival of juveniles.
We used radio‐telemetry to monitor the survival of translocated Giant gartersnakes (Thamnophis gigas)—an imperiled species of semi‐aquatic snakes—in Sacramento County, California, USA. Our study found that adult snakes had lower survival following translocation compared to resident snakes, whereas captive‐reared juveniles showed promising survival estimates in the first 4 months after release.
Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation.
This is a multicenter retrospective ...study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality.
The median age of our cohort was 54 43-64 years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval CI, 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio HR, 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality.
Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years.
Kaplan–Meier (K-M) analysis, the cornerstone of cancer clinical trial interpretation, assumes that censored patients are no more or less likely to experience an event than those followed. We sought ...to investigate the patterns of censoring in surrogate end-points of oncology randomised controlled trials (RCTs) and examine the relationship between censoring in practice-changing treatments that failed to demonstrate survival gain.
In this cross-sectional study of phase III RCTs published in the New England Journal of Medicine, Lancet, and JAMA, between 2010 and 2020, K-M curves of surrogate end-points with statistical significance were extracted. The reverse K-M method (i.e., events and censoring are flipped) was used to examine differential censoring using the analogous reverse hazard ratio and restricted mean survival time. Sensitivity analysis was performed by partially restoring the balance in censoring between study arms.
Of the 73 eligible studies with significant surrogates, 33 (45%) reported significant overall survival benefit (concordant trials), and 40 (55%) did not (discordant trials). The proportion of studies with significant differential censoring in surrogates was 43% (17/40) and 51% (17/33) in discordant and concordant trials, respectively. Trials with a significant censoring imbalance in the experimental arm occurred only in discordant trials (15% vs 0%, odds ratio OR = 12.62, P = 0.033), compared to excessive censoring in the control arm which occurred more in concordant trials (28% vs 52%; OR = 0.36, P = 0.036). Although censoring imbalance occurred in both groups, after sensitivity analysis, 50% of the discordant trials lost their statistical significance, compared to 15% of concordant trials (OR = 5.6, P = 0.0018).
Censoring imbalance between study arms of RCTs suggests a potential systemic bias and raises uncertainty regarding the validity of the results. Informative censoring may explain the inconsistency between therapies that seem to improve disease outcomes without concomitant survival benefit and should trigger further investigation.
•The assumption of uninformative censoring does not hold in many randomised trials.•The reverse Kaplan–Meier and reverse hazard ratio are useful for censoring analysis.•Excessive treatment arm censoring is specific to positive trials with no survival gain.•Fifty percent of trials with imbalanced censoring lose significance after restoring the balance.•Informative censoring explains inconsistencies in trials with discordant outcomes.
Acute lymphoblastic leukemia (ALL) is a debilitating illness that easily occurs in adolescents. microRNAs (miRNAs) are potential biomarkers for multiple diseases. This paper was to elaborate on the ...expression of miR-16-2-3p in childhood ALL and its clinical values on ALL diagnosis and prognosis. First, serum miR-16-2-3p expression in ALL children and healthy volunteers was measured using RT-qPCR. Next, diagnostic potential and prognostic values of miR-16-2-3p on ALL were analyzed through receiver operating characteristic (ROC) curve, Kaplan-Meier survival curve, and multivariate Cox regression analysis, respectively. No significant difference was observed in the clinical baseline data between ALL patients and healthy children. ALL patients showed downregulated serum miR-16-2-3p (0.65 ± 0.27) (p < .01), whose area under the ROC curve was 0.837 with a cut-off value of 0.745 (67.92% sensitivity, 96.94% specificity). ALL patients with higher miR-16-2-3p expression had higher survival rates than those with lower miR-16-2-3p expression. Low miR-16-2-3p expression predicted poor prognosis of ALL patients. After adjusting LDH and lymphomyelocyte proportion (p = 0.003, HR = 0.003, 95%CI = 0.000-0.145), miR-16-2-3p was recognized as an independent prognostic factor for ALL patient survival. Briefly, low serum miR-16-2-3p expression in ALL children could aid ALL diagnosis and predict poor prognosis.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the molecular mechanisms of HCC are still not well ...understood. To identify the candidate genes in the carcinogenesis and progression of HCC, microarray datasets GSE19665, GSE33006 and GSE41804 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. A total of 273 DEGs were identified, consisting of 189 downregulated genes and 84 upregulated genes. The enriched functions and pathways of the DEGs include protein activation cascade, complement activation, carbohydrate binding, complement and coagulation cascades, mitotic cell cycle and oocyte meiosis. Sixteen hub genes were identified and biological process analysis revealed that these genes were mainly enriched in cell division, cell cycle and nuclear division. Survival analysis showed that BUB1, CDC20, KIF20A, RACGAP1 and CEP55 may be involved in the carcinogenesis, invasion or recurrence of HCC. In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of HCC, and provide candidate targets for diagnosis and treatment of HCC.
Data maturity and follow-up in time-to-event analyses Gebski, Val; Garès, Valérie; Gibbs, Emma ...
International journal of epidemiology,
2018-Jun-01, 2018-06-01, 20180601, Letnik:
47, Številka:
3
Journal Article
Recenzirano
Odprti dostop
We propose methods to determine the minimum number of subjects remaining at risk after which Kaplan-Meier survival plots for time-to-event outcomes should be curtailed, as, once the number remaining ...at risk drops below this minimum, the survival estimates are no longer meaningful in the context of the investigation. The size of the decrease of the Kaplan-Meier survival estimate S(t) at time t if one extra event should occur is considered in two ways. In the first approach, the investigator sets a maximum acceptable absolute decrease in S(t) should one extra event occur. In the second, a minimum acceptable number of subjects still at risk is calculated by comparing the size of the decrease in S(t) if an extra event should occur with the variability of the survival estimate had all subjects been followed to that time (confidence interval approach). We recommend calculating both limits for the number still at risk and then making an informed choice in the context of the particular investigation. We explore further how the amount of information actually available can assist in considering issues of data maturity for studies whose outcome of interest is a survival percentage at a particular time point. We illustrate the approaches with a number of published studies having differing sample sizes and censoring issues. In particular, one study was the subject of some controversy regarding how far in time the Kaplan-Meier plot should be extended. The proposed methods allow for limits to be calculated simply using the output provided by most statistical packages.
OBJECTIVENervus intermedius neuralgia (NIN) or geniculate neuralgia is a rare facial pain condition consisting of sharp, lancinating pain deep in the ear and can occur alongside trigeminal neuralgia ...(TN). Studies on the clinical presentation, intraoperative findings, and ultimately postoperative outcomes are extremely limited. The aim of this study was to examine the clinical presentation and surgical findings, and determine pain-free survival after sectioning of the nervus intermedius (NI).METHODSThe authors conducted a retrospective chart review and survey of patients who were diagnosed with NIN at one institution and who underwent neurosurgical interventions. Pain-free survival was determined through chart review and phone interviews using a modified facial pain and quality of life questionnaire and represented as Kaplan-Meier curves.RESULTSThe authors found 15 patients with NIN who underwent microsurgical intervention performed by two surgeons from 2002 to 2016 at a single institution. Fourteen of these patients underwent sectioning of the NI, and 8 of 14 had concomitant TN. Five patients had visible neurovascular compression (NVC) of the NI by the anterior inferior cerebellar artery in most cases where NVC was found. The most common postoperative complaints were dizziness and vertigo, diplopia, ear fullness, tinnitus, and temporary facial nerve palsy. Thirteen of the 14 patients reportedly experienced pain relief immediately after surgery. The mean length of follow-up was 6.41 years (range 8 months to 14.5 years). Overall recurrence of any pain was 42% (6 of 14), and 4 patients (isolated NIN that received NI sectioning alone) reported their pain was the same or worse than before surgery at longest follow-up. The median pain-free survival was 4.82 years ± 14.85 months. The median pain-controlled survival was 6.22 years ± 15.78 months.CONCLUSIONSIn this retrospective review, sectioning of the NI produced no major complications, such as permanent facial weakness or deafness, and was effective for patients when performed in addition to other procedures. After sectioning of the NI, patients experienced 4.8 years pain free and experienced 6.2 years of less pain than before surgery. Alone, sectioning of the NI was not effective. The pathophysiology of NIN is not entirely understood. It appears that neurovascular compression plays only a minor role in the syndrome and there is a high degree of overlap with TN.
Background
Prognostic classification of metastatic melanoma patients treated with anti-PD-1 is of great interest to clinicians.
Objective
We aimed to determine the anti-PD-1 treatment related ...prognostic performance of demographics, clinical and histological prognostic markers and baseline serum S100B and LDH levels in advanced melanoma.
Methods
A total of 200 patients with unresectable metastatic melanoma were included in this retrospective study. 34.5% had stage M1c disease and 11.5% had stage M1d disease at the start of therapy. 30% had pT4b primary melanoma. 55.5% had elevated baseline serum S100B levels and 62.5% had elevated baseline serum LDH levels. We analysed the risk of death using univariate and multivariate Cox proportional-hazards models and the median overall (OS) and progression-free (PFS) survival using the Kaplan-Meier estimator.
Results
The median follow-up time from the start of anti-PD-1 treatment in patients who were alive at the end of the study (N=81) was 37 months (range: 6.1–95.9). The multivariate Cox regression analysis showed that M1c stage (vs. M1a, p=0.005) or M1d stage at the start of therapy (vs. M1a, p=0.001), pT4b category (vs. pT1a, p=0.036), elevated baseline serum S100B levels (vs. normal S100B, p=0.008) and elevated LDH levels (vs. normal LDH, p=0.049) were independently associated with poor survival. The combination of M1d stage, elevated baseline serum S100B and LDH levels and pT4b category was associated with a very high risk of death (HR 4.72 1.81; 12.33). In the subgroup of patients with pT4b primary melanoma, the median OS of patients with normal serum S100B levels was 37.25 months 95% CI 11.04; 63.46), while the median OS of patients with elevated serum S100B levels was 8.00 months 95% CI 3.49; 12.51) (p<0.001); the median OS of patients with normal serum LDH levels was 41.82 months 95% CI 11.33; 72.32), while the median OS of patients with elevated serum LDH levels was 12.29 months 95% CI 4.35; 20.23) (p=0.002).
Conclusion
Our real-world study indicates that the prognostic role of primary melanoma parameters is preserved in anti-PD-1 treated stage IV patients. Furthermore, there seems to be perspective in combining clinical, histological and serum prognostic markers in a prognostic model.
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