Background

Propensity score (PS) methods are increasingly used, even when sample sizes are small or treatments are seldom used. However, the relative performance of the two mainly recommended PS methods, namely PS-matching or inverse probability of treatment weighting (IPTW), have not been studied in the context of small sample sizes.

Methods

We conducted a series of Monte Carlo simulations to evaluate the influence of sample size, prevalence of treatment exposure, and strength of the association between the variables and the outcome and/or the treatment exposure, on the performance of these two methods.

Results

Decreasing the sample size from 1,000 to 40 subjects did not substantially alter the Type I error rate, and led to relative biases below 10%. The IPTW method performed better than the PS-matching down to 60 subjects. When N was set at 40, the PS matching estimators were either similarly or even less biased than the IPTW estimators. Including variables unrelated to the exposure but related to the outcome in the PS model decreased the bias and the variance as compared to models omitting such variables. Excluding the true confounder from the PS model resulted, whatever the method used, in a significantly biased estimation of treatment effect. These results were illustrated in a real dataset.

Conclusion

Even in case of small study samples or low prevalence of treatment, PS-matching and IPTW can yield correct estimations of treatment effect unless the true confounders and the variables related only to the outcome are not included in the PS model.

Background

As a result of reporting bias, or frauds, false or misunderstood findings may represent the majority of published research claims. This article provides simple methods that might help to appraise the quality of the reporting of randomized, controlled trials (RCT).

Methods

This evaluation roadmap proposed herein relies on four steps: evaluation of the distribution of the reported variables; evaluation of the distribution of the reported p values; data simulation using parametric bootstrap and explicit computation of the p values. Such an approach was illustrated using published data from a retracted RCT comparing a hydroxyethyl starch versus albumin-based priming for cardiopulmonary bypass.

Results

Despite obvious nonnormal distributions, several variables are presented as if they were normally distributed. The set of 16 p values testing for differences in baseline characteristics across randomized groups did not follow a Uniform distribution on [0,1] (p = 0.045). The p values obtained by explicit computations were different from the results reported by the authors for the two following variables: urine output at 5 hours (calculated p value < 10-6, reported p ≥ 0.05); packed red blood cells (PRBC) during surgery (calculated p value = 0.08; reported p < 0.05). Finally, parametric bootstrap found p value > 0.05 in only 5 of the 10,000 simulated datasets concerning urine output 5 hours after surgery. Concerning PRBC transfused during surgery, parametric bootstrap showed that only the corresponding p value had less than a 50% chance to be inferior to 0.05 (3,920/10,000, p value < 0.05).

Conclusions

Such simple evaluation methods might offer some warning signals. However, it should be emphasized that such methods do not allow concluding to the presence of error or fraud but should rather be used to justify asking for an access to the raw data.

Background

The best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks.

Methods and results

Three observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55-0.80]) compared to inopressors alone.

Conclusions

In the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.

Unlabelled

Background

In some clinical situations, for which RCT are rare or impossible, the majority of the evidence comes from observational studies, but standard estimations could be biased because they ignore covariates that confound treatment decisions and outcomes.

Methods

Three observational studies were conducted to assess the benefit of Allo-SCT in hematological malignancies of multiple myeloma, follicular lymphoma and Hodgkin's disease. Two statistical analyses were performed: the propensity score (PS) matching approach and the inverse probability weighting (IPW) approach.

Results

Based on PS-matched samples, a survival benefit in MM patients treated by Allo-SCT, as compared to similar non-allo treated patients, was observed with an HR of death at 0.35 (95%CI: 0.14-0.88). Similar results were observed in HD, 0.23 (0.07-0.80) but not in FL, 1.28 (0.43-3.77). Estimated benefits of Allo-SCT for the original population using IPW were erased in HR for death at 0.72 (0.37-1.39) for MM patients, 0.60 (0.19-1.89) for HD patients, and 2.02 (0.88-4.66) for FL patients.

Conclusion

Differences in estimated benefits rely on whether the underlying population to which they apply is an ideal randomized experimental population (PS) or the original population (IPW). These useful methods should be employed when assessing the effects of innovative treatment in non-randomized experiments.

Introduction

Cardiac troponin has been shown to be elevated in one-half of the parturients admitted for post-partum haemorrhage. The purpose of the study was to assess whether increased cardiac troponin was associated with a simultaneous alteration in haemoglobin tissue oxygen saturation in peripheral muscles in post-partum haemorrhage.

Methods

Tissue haemoglobin oxygen saturation of thenar eminence muscle (StO2) was measured via near-infrared spectroscopy technology. Two sets of StO2 parameters (both isolated baseline and during forearm ischaemia-reperfusion tests) were collected at two time points: upon intensive care unit admission and prior to intensive care unit discharge. Comparisons were performed using Wilcoxon paired tests, and univariate associations were assessed using logistic regression model and Wald tests.

Results

The 42 studied parturients, admitted for post-partum haemorrhage, had clinical and biological signs of severe blood loss. Initial cardiac troponin I was increased in 24/42 parturients (0.43 +/- 0.60 microrg/l). All measured parameters of muscular haemoglobin oxygen saturation, including Srecovery, were also altered at admission and improved together with improved haemodynamics, when bleeding was controlled. Multivariate analysis showed that muscular Srecovery <3%/second at admission was strongly associated with increased cardiac troponin.

Conclusions

Our study confirmed the high incidence of increased cardiac troponin, and demonstrated the simultaneous impairment in the reserve of oxygen delivery to peripheral muscles in parturients admitted for severe post-partum haemorrhage.

Objective

To investigate risk factors and subphenotypes associated with long term symptoms and outcomes after hospital admission for covid-19.

Design

Prospective, multicentre observational study.

Setting

93 hospitals in France.

Participants

Data from 2187 adults admitted to hospital with covid-19 in France between 1 February 2020 and 30 June 2021.

Main outcome measures

Primary endpoint was the total number of persistent symptoms at six months after hospital admission that were not present before admission. Outcomes examined at six months were persistent symptoms, Hospital Anxiety and Depression Scale, six minute walk test distances, 36-Item Short Form Health Survey scores, and ability to resume previous professional activities and self-care. Secondary endpoints included vital status at six months, and results of standardised quality-of-life scores. Additionally, an unsupervised consensus clustering algorithm was used to identify subphenotypes based on the severity of hospital course received by patients.

Results

1109 (50.7%) of 2187 participants had at least one persistent symptom. Factors associated with an increased number of persistent symptoms were in-hospital supplemental oxygen (odds ratio 1.12, 95% confidence interval 1 to 1.24), no intensive care unit admission (1.15, 1.01 to 1.32), female sex (1.33, 1.22 to 1.45), gastrointestinal haemorrhage (1.51, 1.02 to 2.23), a thromboembolic event (1.66, 1.17 to 2.34), and congestive heart failure (1.76, 1.27 to 2.43). Three subphenotypes were identified: including patients with the least severe hospital course (based on ventilatory support requirements). Although Hospital Anxiety and Depression Scale scores were within normal values for all groups, patients of intermediate severity and more comorbidities had a higher median Hospital Anxiety and Depression Scale score than did the other subphenotypes. Patients in the subphenotype with most severe hospital course had worse short form-36 scores and were less able to resume their professional activity or care for themselves as before compared with other subphenotypes.

Conclusions

Persistent symptoms after hospital admission were frequent, regardless of acute covid-19 severity. However, patients in more severe subphenotypes had a significantly worse functional status and were less likely to resume their professional activity or able to take care of themselves as before.

Trial registration

NCT04262921.

Background

Intensive care unit (ICU) survivors have reduced long-term survival compared to the general population. Identifying parameters at ICU discharge that are associated with poor long-term outcomes may prove useful in targeting an at-risk population. The main objective of the study was to identify clinical and biological determinants of death in the year following ICU discharge.

Methods

FROG-ICU was a prospective, observational, multicenter cohort study of ICU survivors followed 1 year after discharge, including 21 medical, surgical or mixed ICUs in France and Belgium. All consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 h following ICU admission and discharged from ICU were included. The main outcome measure was all-cause mortality at 1 year after ICU discharge. Clinical and biological parameters on ICU discharge were measured, including the circulating cardiovascular biomarkers N-terminal pro-B type natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and soluble-ST2. Socioeconomic status was assessed using a validated deprivation index (FDep).

Results

Of 1570 patients discharged alive from the ICU, 333 (21%) died over the following year. Multivariable analysis identified age, comorbidity, red blood cell transfusion, ICU length of stay and abnormalities in common clinical factors at the time of ICU discharge (low systolic blood pressure, temperature, total protein, platelet and white cell count) as independent factors associated with 1-year mortality. Elevated biomarkers of cardiac and vascular failure independently associated with 1-year death when they are added to multivariable model, with an almost 3-fold increase in the risk of death when combined (adjusted odds ratio 2.84 (95% confidence interval 1.73-4.65), p < 0.001).

Conclusions

The FROG-ICU study identified, at the time of ICU discharge, potentially actionable clinical and biological factors associated with poor long-term outcome after ICU discharge. Those factors may guide discharge planning and directed interventions.

Trial registration

ClinicalTrials.gov NCT01367093 . Registered on 6 June 2011.