Oxygen treatment after perinatal hypoxia-ischemia reduces neuronal damage at short survival times, but worsens injury with long-term survival

AimsACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population.MethodsIn 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0–29.6 years).ResultsBy 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%.ConclusionFor patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.

Download Full-text

Renal Replacement Therapy in Patients With Stage IV Cancer Admitted to the Intensive Care Unit With Acute Kidney Injury at a Comprehensive Cancer Center Was Not Associated With Survival

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909120902115 ◽

2020 ◽

Vol 37 (9) ◽

pp. 707-715

Author(s):

Ala Abudayyeh ◽

Juhee Song ◽

Maen Abdelrahim ◽

Ibrahim Dahbour ◽

Valda D. Page ◽

...

Keyword(s):

Intensive Care Unit ◽

Kidney Injury ◽

Stage Iv ◽

Inpatient Mortality ◽

Survival Times ◽

Term Survival ◽

Long Term Survival ◽

Time Points ◽

Stage Iv Cancer

Introduction: In patients with advanced cancer, prolongation of life with treatment often incurs substantial emotional and financial expense. Among hospitalized patients with cancer since acute kidney injury (AKI) is known to be associated with much higher odds for hospital mortality, we investigated whether renal replacement therapy (RRT) use in the intensive care unit (ICU) was a significant independent predictor of worse outcomes. Methods: We retrospectively reviewed patients admitted in 2005 to 2014 who were diagnosed with stage IV solid tumors, had AKI, and a nephrology consult. The main outcomes were survival times from the landmark time points, inpatient mortality, and longer term survival after hospital discharge. Logistic regression and Cox proportional regression were used to compare inpatient mortality and longer term survival between RRT and non-RRT groups. Propensity score-matched landmark survival analyses were performed with 2 landmark time points chosen at day 2 and at day 7 from ICU admission. Results: Of the 465 patients with stage IV cancer admitted to the ICU with AKI, 176 needed RRT. In the multivariate logistic regression model after adjusting for baseline serum albumin and baseline maximum Sequential Organ Failure Assessment (SOFA), the patients who received RRT were not significantly different from non-RRT patients in inpatient mortality (odds ratio: 1.004 [95% confidence interval: 0.598-1.684], P = .9892). In total, 189 patients were evaluated for the impact of RRT on long-term survival and concluded that RRT was not significantly associated with long-term survival after discharge for patients who discharged alive. Landmark analyses at day 2 and day 7 confirmed the same findings. Conclusions: Our study found that receiving RRT in the ICU was not significantly associated with inpatient mortality, survival times from the landmark time points, and long-term survival after discharge for patients with stage IV cancer with AKI.

Download Full-text

Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?

Statistical Methods in Medical Research ◽

10.1177/0962280218780856 ◽

2018 ◽

Vol 28 (8) ◽

pp. 2475-2493 ◽

Cited By ~ 4

Author(s):

NR Latimer ◽

IR White ◽

KR Abrams ◽

U Siebert

Keyword(s):

Treatment Effect ◽

Failure Time ◽

Survival Function ◽

Experimental Treatment ◽

Control Group ◽

Survival Times ◽

Term Survival ◽

Long Term Survival ◽

Treatment Switching

Treatment switching often has a crucial impact on estimates of effectiveness and cost-effectiveness of new oncology treatments. Rank preserving structural failure time models (RPSFTM) and two-stage estimation (TSE) methods estimate ‘counterfactual’ (i.e. had there been no switching) survival times and incorporate re-censoring to guard against informative censoring in the counterfactual dataset. However, re-censoring causes a loss of longer term survival information which is problematic when estimates of long-term survival effects are required, as is often the case for health technology assessment decision making. We present a simulation study designed to investigate applications of the RPSFTM and TSE with and without re-censoring, to determine whether re-censoring should always be recommended within adjustment analyses. We investigate a context where switching is from the control group onto the experimental treatment in scenarios with varying switch proportions, treatment effect sizes, treatment effect changes over time, survival function shapes, disease severity and switcher prognosis. Methods were assessed according to their estimation of control group restricted mean survival that would be observed in the absence of switching, up to the end of trial follow-up. We found that analyses which re-censored usually produced negative bias (i.e. underestimating control group restricted mean survival and overestimating the treatment effect), whereas analyses that did not re-censor consistently produced positive bias which was often smaller in magnitude than the bias associated with re-censored analyses, particularly when the treatment effect was high and the switching proportion was low. The RPSFTM with re-censoring generally resulted in increased bias compared to the other methods. We believe that analyses should be conducted with and without re-censoring, as this may provide decision-makers with useful information on where the true treatment effect is likely to lie. Incorporating re-censoring should not always represent the default approach when the objective is to estimate long-term survival times and treatment effects.

Download Full-text

Long Term Oxygen Treatment In COPD Is Associated With Greater Hospital And ICU Length Of Stays During Acute COPD Hospitalizations And Worse Long-Term Survival

10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1496 ◽

2010 ◽

Author(s):

Aaron Czysz ◽

Carla Grabianowski ◽

John Gaughan ◽

Nathaniel Marchetti ◽

Gerard J. Criner

Keyword(s):

Term Survival ◽

Long Term Survival ◽

Oxygen Treatment

Download Full-text

Long-term survival of combined ablation therapy and tremelimumab with or without durvalumab in advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16689 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16689-e16689

Author(s):

M. Cecilia Monge B. ◽

Changqing Xie ◽

John McVey ◽

Donna Mabry-Hrones ◽

Austin Duffy ◽

...

Keyword(s):

Overall Survival ◽

Immune Checkpoint ◽

Advanced Hepatocellular Carcinoma ◽

Survival Times ◽

Term Survival ◽

Long Term Survival ◽

Advanced Hcc ◽

Select Group ◽

Flat Dose

e16689 Background: Immune checkpoint inhibitor therapy has recently been approved for the treatment of patients with Hepatocellular Cancer (HCC). Data on long-term survival is lacking and the predictors of good outcomes are unknown. The combination of locoregional therapies (transarterial chemoembolization or radiofrequency ablation) plus tremelimumab (trem) with or without durvalumab (durva) was studied in patients with advanced HCC. We report the long-term survival and analyze predictors of good response in two trials of immune checkpoint and ablation treatment in advanced HCC. Methods: Adult patients (pts) with pathologically confirmed HCC with advanced or sorafenib refractory disease who satisfied the eligibility criteria were enrolled in the studies (NCT02821754, NCT01853618). They received treatment with trem, 10 mg per kilogram every 4 weeks for six doses followed by 3 monthly infusions (23 pts) or trem 75 mg flat dose every 28 days for four doses and then durva 1500 mg flat dose every 28 days (35 pts). Subtotal radiofrequency or chemoablation was done on day 36. Results: The average overall survival in the 58 pts was 10.1 months (range 0.9 to 74.2 months); 41.6% were alive at 12 months and 5.5 % were alive at 61 months. A select group of patients had exceptional overall survivals up to 67 months. Predictors of improved overall survival included the presence of higher grade immune related (irAEs) (OR 0.235, p = 0.075) and a partial or stable disease response per RECIST. No new late toxic effects were noted during this long term follow up. Conclusions: Impressive overall survival times of up to 68.8 months were observed with ICI and subtotal ablation in patients with advanced HCC; the presence of irAEs and the tumor response per RECIST may be predictive of better overall survivals. To our knowledge this has not been previously reported in the literature. Clinical trial information: NCT02821754,NCT01853618 .

Download Full-text

Uncomplicated gallbladder mucoceles – is it better for prognosis to perform cholecystectomy or medically manage?

Veterinary Evidence ◽

10.18849/ve.v6i2.395 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Rachel T. Griffiths ◽

Wanda J. Gordon-Evans

Keyword(s):

Research Question ◽

Direct Analysis ◽

Individual Case ◽

Clinical Expertise ◽

Survival Times ◽

Bottom Line ◽

Term Survival ◽

Long Term Survival ◽

The Individual

PICO question In dogs with an uncomplicated gallbladder mucocele, is the long-term survival when surgically managed superior, inferior, or equal to those medically managed? Clinical bottom line Category of research question Treatment and prognosis The number and type of study designs reviewed Three papers were critically reviewed. All of the studies were retrospective analyses of medical records, two of which were cohort studies, and one which was a case control study Strength of evidence Weak Outcomes reported There is some evidence that surgical management of gallbladder mucoceles is associated with longer survival times than medically managed cases, although there is no direct analysis of uncomplicated vs complicated cases Conclusion We cannot clearly make a conclusion based on the available evidence. To date, there is only one retrospective analysis that directly compares the long-term survival of cases medically vs surgically managed, but this study does not separate uncomplicated vs complicated cases of gallbladder mucocele. In order to more accurately determine which type of treatment should be recommended for uncomplicated cases of gallbladder mucoceles, a prospective study comparing long-term survival with each treatment should be performed. These studies should also standardise medical management in order to more accurately compare survival time to surgical treatment How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Download Full-text

Lower Plasma Melatonin Levels Predict Worse Long-Term Survival in Pulmonary Arterial Hypertension

Journal of Clinical Medicine ◽

10.3390/jcm9051248 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1248 ◽

Cited By ~ 1

Author(s):

Zongye Cai ◽

Theo Klein ◽

Laurie W. Geenen ◽

Ly Tu ◽

Siyu Tian ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Survival Times ◽

Term Survival ◽

Long Term Survival ◽

Liquid Chromatography Tandem Mass ◽

Treatment Naïve ◽

Pulmonary Arterial ◽

Endogenous Melatonin

Exogenous melatonin has been reported to be beneficial in the treatment of pulmonary hypertension (PH) in animal models. Multiple mechanisms are involved, with melatonin exerting anti-oxidant and anti-inflammatory effects, as well as inducing vasodilation and cardio-protection. However, endogenous levels of melatonin in treatment-naïve patients with PH and their clinical significance are still unknown. Plasma levels of endogenous melatonin were measured by liquid chromatography-tandem mass spectrometry in PH patients (n = 64, 43 pulmonary arterial hypertension (PAH) and 21 chronic thromboembolic PH (CTEPH)) and healthy controls (n = 111). Melatonin levels were higher in PH, PAH, and CTEPH patients when compared with controls (Median 118.7 (IQR 108.2–139.9), 118.9 (109.3–147.7), 118.3 (106.8–130.1) versus 108.0 (102.3–115.2) pM, respectively, p all <0.001). The mortality was 26% (11/43) in the PAH subgroup during a long-term follow-up of 42 (IQR: 32–58) months. Kaplan–Meier analysis showed that, in the PAH subgroup, patients with melatonin levels in the 1st quartile (<109.3 pM) had a worse survival than those in quartile 2–4 (Mean survival times were 46 (95% CI: 30–65) versus 68 (58–77) months, Log-rank, p = 0.026) with an increased hazard ratio of 3.5 (95% CI: 1.1–11.6, p = 0.038). Endogenous melatonin was increased in treatment-naïve patients with PH, and lower levels of melatonin were associated with worse long-term survival in patient with PAH.

Download Full-text