Faculty Opinions recommendation of Semiparametric analysis of short-term and long-term hazard ratios with two-sample survival data.

Author(s):  
Gudrun Simons
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14032-e14032
Author(s):  
Fayez A. Quereshy ◽  
Jensen T.C. Poon ◽  
Wai Lun Law

e14032 Background: Stenting as a bridge to surgery has been increasingly applied in cases of acute left-sided colonic obstruction. This study aims to evaluate both the short and long-term outcomes associated with colonic stenting as a bridge to surgery in patients with obstructing adenocarcinoma of the colon. Methods: Patients with potentially curable acute left-sided colonic obstruction treated with stenting as a bridge to surgery (28) or with emergency surgical resection (39) from January 1998 to December 2008 were identified using a prospectively maintained database. Short-term data on post-operative mortality, morbidity, necessity of intensive care, and length of hospital stay were compared. Disease-free and overall survival data were also analyzed. Results: Patients within the two study arms had similar demographic profiles. Patients receiving preoperative stenting had a higher likelihood of a laparoscopic resection (p<0.001). Further, the emergency surgery group had a higher rate of post-operative complications (p=0.024), rate of ICU admission (p=0.013), and longer total length of stay (9 vs. 12 days, p=0.001). With a median follow-up of 26.5 and 31.3 months for the stenting and surgical resection groups respectively, there was no difference in overall and disease-free survival (overall survival = 30 vs. 31 months, p=0.858; DFS = 13 vs. 12 months, p=0.989). As well, there was no difference in the rate of systemic recurrences (8 vs. 13, p=0.991). Conclusions: Stenting as a bridge to surgery is a safe treatment strategy in the management of patients with acute left-sided colonic obstruction with improved short-term outcomes and comparable long-term oncologic results.


2010 ◽  
Vol 4 (1) ◽  
pp. 173-177 ◽  
Author(s):  
Mette Charlot ◽  
Christian Torp-Pedersen ◽  
Nana Valeur ◽  
Marie Seibæk ◽  
Peter Weeke ◽  
...  

Background: Anaemia has been demonstrated as a risk factor in patients with heart failure over periods of a few years, but long term data are not available. We examined the long-term risk of anaemia in heart failure patients during 15 years of follow-up. Methods: We evaluated survival data for 1518 patients with heart failure randomized into the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trial. The follow-up time was from 13 to 15 years. After 15 years 11.5% of the patients were still alive. Results: Anaemia was present in 34% of the patients. 264 (17%) had mild, 152 (10%) had moderate and 98 (7%) had severe anaemia. Hazard ratio of death for patients with mild anaemia compared with patients with no anaemia was 1.27 (1.11-1.45, p<0.001), for moderate anaemia 1.48 (1.24-1.77, p<0.001) and for severe anaemia 1.82 (1.47-2.24, p<0.001), respectively. In multivariable analyses anaemia was still associated with increased mortality with hazard ratios of 1.19 (1.04–1.37, p=0.014) for mild anaemia, 1.23 (1.03–1.48, p=0.024) for moderate anaemia and 1.33 (1.07–1.66, p=0.010) for severe anaemia, respectively. In landmark analysis the increased mortality for mild anaemia was only significant during the first 2 years, while moderate anaemia remained significant for at least 5 years. There were too few patients left with severe anaemia after 5 years to evaluate the importance on mortality beyond this time. Conclusion: Anaemia at the time of diagnosis of heart failure is an independent factor for mortality during the following years but loses its influence on mortality over time.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17117-17117 ◽  
Author(s):  
L. Weisenthal

17117 Background: Gefitinib (GEF) may act by inhibiting anti-apoptotic signals transduced by mutant EGFR kinase (Science 305:1163,04). Cell culture assays with cell death endpoints could be informative for GEF activity. Methods: We tested 568 biopsies of fresh human tumors (TUM) with 2 concentrations of GEF (22 and 11 μg/ml) for 96 hrs, each with 2 separate cell death endpoints (DISC and MTT), detailed methods http://weisenthal.org/w_ovarian_cp.pdf . Results classified as resistant (RES), intermediate (INT), or sensitive (SEN) based on means and standard deviations of training set data (ref ibid), reported prospectively to 3 different physicians: surgeon, pathologist, and oncologist. Assay evaluability rate > 90%. Results: Based on overall % control cell death, the following TUM showed (on average) no greater RES or SEN than the universe of 568 assays: NSCLC (n = 72), colon (33), breast (106), ovarian (109), melanoma (23), pancreatic (20), endometrial (12). The following showed (on avg) significantly greater RES: soft tissue sarcomas (n = 24), carcinoid/islet (16), renal (15), and mesothelioma (8). For NSCLC, there was no avg difference between female (32) vs male (35) or untreated (34) vs previously treated (38). For 32 unRxd pts with survival data, there was no significant difference in overall surv for 20 pts with prospectively reported GEF RES (GR) assays vs 12 pts with SEN or INT (GSI) assays. For 31 pts with prior chemoRx (med surv = 155 days), there was significant survival disadvantage for 14 pts with prospectively reported GR vs 17 pts with GSI (median 85 vs 380 days, P2 < 0.0001, HR 3.7; 95% C.I. 2.6–19). For pts with known post-assay Rx, there were 7 pts with GSI subsequently receiving GEF or erlotinib (ERLOT), with med surv = 485 days; 9 pts with GSI not receiving GEF or ERLOT, med surv = 135 days; 10 pts with GR not receiving GEF or ERLOT, med surv = 76 days, and 3 pts with GR receiving GEF or ERLOT, med surv = 75 days. Survival of group of 7 pts was significantly greater than those of groups of 9, 10, and 3 pts (P2 = 0.02, P2 < 0.0001, and P2 = 0.002, respectively). Conclusions: GEF-induced cell death in cultures of fresh TUM from prev-treated NSCLC pts may identify pts with favorable prognosis, particularly when treated with GEF or ERLOT. [Table: see text]


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Sabine Schmid ◽  
Dirk Klingbiel ◽  
Stefan Aebi ◽  
Aron Goldhirsch ◽  
Christoph Mamot ◽  
...  

Abstract Background The impact of HER2-targeted therapy alone followed by the addition of chemotherapy at disease progression (PD) versus upfront combination was investigated by the SAKK 22/99 trial. The aim of this exploratory analysis of the SAKK 22/99 trial was to characterize the specific subset of patients deriving long-term benefit from trastuzumab monotherapy alone and to identify potential predictive factors of long-term response. Methods This is an unplanned post-hoc analysis of patients randomized to Arm A (trastuzumab monotherapy). Patients were divided in two groups: patients with durable clinical benefit from trastuzumab monotherapy and short-term responders without durable clinical benefit from trastuzumab monotherapy Univariate and multivariate analyses of clinical characteristics correlating with response duration was performed. Results Eighty six patients were randomized in arm A, 24 patients (28%) were long-term responders and 62 (72%) were short-term responders with a 5y-overall survival (OS) of 54% (95% CI 31–72) and of 18% (95%CI 10–30), respectively. Absence of ER expression, absence of PgR expression and presence of visceral disease emerged as possible negative predictive factors for durable clinical benefit. Conclusion Durable clinical benefit can be achieved with trastuzumab monotherapy in a subgroup of HER2-positive patients with advanced disease and it is predictive for longer OS. Further investigations of predictive biomarkers are necessary to better characterize this subgroup of patients and develop further de-escalating strategies. Trial registration NCT00004935; first posted 27.01.2003, retrospectively registered.


Rheumatology ◽  
2020 ◽  
Author(s):  
Jennifer C E Lane ◽  
James Weaver ◽  
Kristin Kostka ◽  
Talita Duarte-Salles ◽  
Maria Tereza F Abrahao ◽  
...  

Abstract Objectives Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA. Methods We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 &lt;40%. Results A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis. Conclusion HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation. Trial registration Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.


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