Whether adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis would result in a lower incidence of deep-vein thrombosis than pharmacologic thromboprophylaxis alone is uncertain.
Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS.This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance.Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P=0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47-1.51; P=0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47-1.64; P=0.68).These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.
The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients.
AbstractBackground The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. Methods In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8–1.2 g/kg/day). The primary outcome is 90-day all-cause mortality, and other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30–25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. Conclusion Ethics approval was obtained from the King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R ). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings Trial registration: ClinicalTrials.gov Identifier: NCT04475666. Registered on July 17, 2020 https://clinicaltrials.gov/ct2/show/NCT04475666
Background: Methods for handling missing data in clinical research have been getting more attentions over last few years. Contemplation of missing data in any study is vital as they may lead to considerable biases and can have an impact on the power of the study.
Objective: This manuscript is dedicated to present different techniques to handle missing observations obtained from repeatedly measured pain score data on palliative cancer.
Methods: This problem caused by subjects drop out before completion of the study. The reason for dropout or withdrawal may be related to study (e.g., adverse event, death, unpleasant study procedures, lack of improvement) or unrelated to the study (e.g., moving away, unrelated disease). The dropout might be very common on studies on palliative cancer patients. The Palliative treatment is designed to relieve symptoms, and improve the quality of life and can be used at any stage of an illness if there are troubling symptoms, such as pain or sickness.
Results: The mean(SD) of observed pain score was 3.638(3.156) whereas the imputed mean values were 3.615(2.980), 3.618(2.954), 3.577(2.892), 3.560(2.999) and 3.627(2.949) respectively for the imputation methods regression, predictive mean matching, propensity score, EM algorithm and MCMC methods for pain score values at visit3.
Interpretation and Conclusion: The EM algorithm shows the least percentage change from observed values in both visits followed by predictive mean matching method and MCMC methods. The multiple imputation techniques have few advantages; the imputed values are drawsfrom a distribution, so they inherently contain some variation by introducing an additional form of error in the parameter estimates across the imputation
PurposePelvic organs are naturally prone to positional and volumetric changes over time. These individual organ changes may result in variations in the clinical target volume (CTV) position and shape. Planning target volume (PTV) that encompasses the CTV with some margins to account for such uncertainties in patient positioning, organ motion, and beam geometry is universally accepted today in radiotherapy. Keeping this view in mind, the present study has been planned in order to determine the setup error (random and systematic) in patients of carcinoma cervix and rectum image-guided radiotherapy and to propose a population-based three-dimensional CTV to PTV margins in IGRT scenario.Materials and methodsThe mean margin displacements of 61 patients measured through different directions. The proposed method is used to estimate margins of displacement of specific CTV dosing. A further method is illustrated to simulate the dose received by the CTV. The margin distance compared with Van Herk model through consideration of systematic and random errors. Different site-wise displacements were measured and compared. The CTV performance dosimetry has been carried through proposed model and compared with the traditional margin for each of the datasets.ResultsThe PTV margins obtained on lateral, longitudinal and vertical sides on Cervix site are 0.91, 1.93 and 0.96 [Van Hark's formula] and 0.84, 1.79 and 0.89 through proposed formula. It can be noted that in both the cases, the respective margin obtained through proposed method was lesser in comparison to that of Van Hark's method.ConclusionsThe presence of heterogeneity in patient's random error is natural. This random error is highly influential on radiotherapy margin widths of the patients. The Bayesian statistics are useful to deal with such a problem. In this article, a simple and well-defined model is adopted to deal with the patient's heterogeneity problem. It has been observed that the model accounted the variability in the margin estimation. The variation in margin can be extended from one cancer site to another cancer site.
The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.
Abstract Background Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2–2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8–1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. Methods The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. Discussion The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. Trial registration ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.
Abstract Background This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. Methods This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4–7 (at least active standing), 1–3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. Results Of 1708 patients, only 85 (5.0%) had early mobility level 4–7 and 356 (20.8%) level 1–3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4–7 and 1–3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4–7 group, 7/348 (2.0%) patients in mobility 1–3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4–7 and 1–3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4–7 and 1–3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively). Conclusions Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable. Trial registration The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).
Importance Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, −8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, −3.1% [95% CI, −14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration ClinicalTrials.gov Identifier: NCT04477668
