Objective We sought to determine whether 4000 IU/d (vs 2000 IU/d) of vitamin D during pregnancy is safe and improves maternal/neonatal 25-hydroxyvitamin D 25(OH)D in a dose-dependent manner. Study ...Design A total of 257 pregnant women 12-16 weeks' gestation were enrolled. Randomization to 2000 vs 4000 IU/d followed 1-month run-in at 2000 IU/d. Participants were monitored for hypercalciuria, hypercalcemia, and 25(OH)D status. Results Maternal 25(OH)D (n = 161) increased from 22.7 ng/mL (SD 9.7) at baseline to 36.2 ng/mL (SD 15) and 37.9 ng/mL (SD 13.5) in the 2000 and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups ( P < .01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D was 22.1 ± 10.3 ng/mL in 2000 IU and 27.0 ± 13.3 ng/mL in 4000 IU groups ( P = .024). After controlling for race and study site, preterm birth and labor were inversely associated with predelivery and mean 25(OH)D, but not baseline 25(OH)D. Conclusion Maternal supplementation with vitamin D 2000 and 4000 IU/d during pregnancy improved maternal/neonatal vitamin D status. Evidence of risk reduction in infection, preterm labor, and preterm birth was suggestive, requiring additional studies powered for these endpoints.
The question stem is the statement or question to which a response is sought. Each question should focus on a single construct. Question stems should contain fewer than 20 words and be easy to ...understand and interpret,5,13 nonjudgmental and unbiased.13 Investigators should phrase questions in a socially and culturally sensitive manner. They should avoid absolute terms (e.g., "always," "none" or "never"),11 abbreviations and complex terminology.2 Investigators should specify the perspective from which questions should be addressed, particularly for questions about attitudes that may elicit different responses depending on how they are worded.14 The language used influences the response formats used, which may affect the response rate. Demonstrative questions are often followed by binary responses, whereas question stems requesting respondents to rank items or elicit their opinions should adopt a neutral tone. The wording of the question and the order of response categories can influence the responses obtained.3,15 Moreover, the manner in which question stems and responses are synthesized and presented can influence potential respondents' decisions to initiate and complete a questionnaire.3 * "Other" response options: Providing an "other" response option or requesting "any other comments" allows for unanticipated answers, alters the power balance between investigators and respondents,18 and may enhance response rates to self-administered questionnaires.3 During questionnaire testing, "other" response options can help to identify new issues or elaborate on closed response formats.18 Members of the ACCADEMY (Academy of Critical Care: Development, Evaluation and Methodology) Group: Dr. Neill K.J. Adhikari, Sunnybrook Health Sciences Centre, Sunnybrook Research Institute and Interdepartmental Division of Critical Care, Toronto, Ont.; Donald Arnold, Department of Medicine, McMaster University, Hamilton, Ont.; Dr. Karen E.A. Burns, St. Michael's Hospital, the Interdepartmental Division of Critical Care, Keenan Research Centre and the Li Ka Shing Knowledge Institute, Toronto, Ont.; Dr. Karen Choong, Department of Pediatrics and Division of Critical Care, McMaster Children's Hospital, Hamilton, Ont.; Dr. Deborah J. Cook MD MSc, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont.; Dr. Cynthia Cupido, Department of Pediatrics and Division of Critical Care, McMaster Children's Hospital, Hamilton, Ont.; Ines De Campos RN, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., and St. Michael's Hospital, Toronto, Ont.; Dr. Mark Duffett BScPharm, Department of Pharmacy and Division of Critical Care, McMaster Children's Hospital, and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont.; Dr. Francois Lamontagne, Department of Clinical Epidemiology and Biostatics, McMaster University, Hamilton, Ont.; Dr. Wendy Lim, Department of Medicine, McMaster University, Hamilton, Ont.; and Dr. Maureen O. Meade MD MSc, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont.
Purpose
Invasive mechanical ventilation is a common form of life support provided to critically ill patients. Frailty is an emerging prognostic factor for poor outcome in the Intensive Care Unit ...(ICU); however, its association with adverse outcomes following invasive mechanical ventilation is unknown. We sought to evaluate the association between frailty, defined by the Clinical Frailty Scale (CFS), and outcomes of ICU patients receiving invasive mechanical ventilation.
Methods
We performed a retrospective analysis (2011–2016) of a prospectively collected registry from two hospitals of consecutive ICU patients ≥ 18 years of age receiving invasive mechanical ventilation. CFS scores were based on recorded pre-admission function at the time of hospital admission. The primary outcome was hospital mortality. Secondary outcomes included discharge to long-term care, extubation failure at time of first liberation attempt, and tracheostomy.
Results
We included 8110 patients, and 2529 (31.2%) had frailty (CFS ≥ 5). Frailty was associated with increased odds of hospital death (adjusted odds ratio aOR: 1.24 95% confidence interval CI 1.10–1.40) and discharge to long-term care (aOR 1.21 95% CI 1.13–1.35). As compared to patients without frailty, patients with frailty had increased odds of extubation failure (aOR 1.17 95% CI 1.04–1.37), hospital death following extubation failure (aOR 1.18 95% CI 1.07–1.28), tracheostomy (aOR 1.17 95% CI 1.01–1.36), and hospital death following tracheostomy (aOR 1.14 95% CI 1.03–1.25).
Conclusions
The presence of frailty among patients receiving mechanical ventilation is associated with increased odds of hospital mortality, discharge to long-term care, extubation failure, and need for tracheostomy.
Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to ...underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality.
We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing.
We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range IQR 2-4) and 6 days (stool; IQR 4.25-6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = - 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045).
The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients.
ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.
The use of noninvasive ventilation for patients with cardiogenic pulmonary edema and acute respiratory failure has been studied extensively. We identified 20 relevant ...RCTs.42-46,48-51,53-57,59,61,62,64-66 These trials examined the use of noninvasive posi tive-pressure ventilation plus usual therapy versus usual therapy alone,48,49,53 continuous positive airway pressure by mask plus usual therapy versus usual therapy alone,42-44,46,51,55,66 continuous positive airway pressure by mask plus usual therapy versus noninvasive positive-pressure ventilation plus usual therapy45,54,57,59,61,62 or all three of these treatments.50,56,64,65 Before publication of a recent large RCT,65 which accounted for 40% of all patients who have been studied in RCTs of continuous positive airway pressure for cardiogenic pulmonary edema and 70% of patients receiving noninvasive positive-pressure ventilation for this indication, five separate systematic reviews162-166 had consistently demonstrated a significant reduction in endotracheal intubation with both types of noninvasive ventilation. When this large trial was included in the metaanalysis, there was a trend toward reduction in endotracheal intubation with noninvasive positive- pressure ventilation (RR 0.55, 95% CI 0.29-1.03) and a significant reduction in endotracheal intubation with continuous positive airway pressure by mask (RR 0.42, 95% CI 0.28- 0.63) relative to oxygen alone. Notably, this recent large trial65 differed from most others, in that patients who met the criteria for treatment failure were allowed to cross over to one of the two forms of noninvasive ventilation rather than undergoing insertion of an endotracheal tube. Although the rate of endotracheal intubation did not differ between arms, a much higher proportion of patients in the oxygen arm crossed over to noninvasive ventilation (56/367 patients v. 5/346 from continuous positive airway pressure to noninvasive positive-pressure ventilation and 12/356 from noninvasive positive-pressure ventilation to continuous positive airway pressure). In addition, the proportion of patients who did not remain in their assigned treatment arm because of respiratory distress was significantly higher in the oxygen-only arm (8.4% v. 3.4% for noninvasive positive-pressure ventilation and 1.4% for continuous positive airway pressure; p < 0.001). Because of the potential for crossover in this trial to confound the outcomes of endo tracheal intubation and hospital mortality, we considered the outcome of "treatment failure" in developing our final guideline statement. Pooled treatment failure for all trials was sig nificantly lower for both noninvasive positivepressure ventilation (RR 0.36, 95% CI 0.25- 0.51) and continuous positive airway pressure (RR 0.23, 95% CI 0.17-0.32). Including all trials, there was a trend toward lower hospital mortality (for noninvasive positive-pressure ventilation, RR 0.84, 95% CI 0.63-1.13; for continuous positive airway pressure, RR 0.73, 95% CI 0.51-1.05). Two RCTs studied noninvasive positivepressure ventilation in patients with communityacquired pneumonia and acute hypoxemic res piratory failure but no prior history of COPD. In one trial, patients with COPD were included, and results for patients who did and did not have this condition were reported separately.38 In the subgroup of patients who did not have COPD (n = 33), the addition of noninvasive positivepressure ventilation did not reduce endotracheal intubation (6/16 v. 8/17 in control group) or hospital mortality (6/16 v. 4/17). In the other trial, which involved patients with acute hypoxemic respiratory failure but no underlying COPD, there was benefit (reduced endotracheal intubation and ICU mortality) for the subgroup of patients (n = 34) with severe communityacquired pneumonia.39 For these two small subgroups (67 patients in total) from two RCTs, the results were conflicting regarding the addition of noninvasive positive-pressure ventilation to usual therapy for patients with severe com munity-acquired pneumonia but no prior history of COPD (pooled results: RR 0.54, 95% CI 0.24-1.17 for endotracheal intubation and RR 0.70, 95% CI 0.13-3.63 for hospital mortality). We did not identify any RCTs on the use of continuous positive airway pressure for patients with severe community-acquired pneumonia and without COPD.
Objective To assess the reporting, extent, and handling of loss to follow-up and its potential impact on the estimates of the effect of treatment in randomised controlled trials.Design Systematic ...review. We calculated the percentage of trials for which the relative risk would no longer be significant under a number of assumptions about the outcomes of participants lost to follow-up.Data sources Medline search of five top general medical journals, 2005-07.Eligibility criteria Randomised controlled trials that reported a significant binary primary patient important outcome.Results Of the 235 eligible reports identified, 31 (13%) did not report whether or not loss to follow-up occurred. In reports that did give the relevant information, the median percentage of participants lost to follow-up was 6% (interquartile range 2-14%). The method by which loss to follow-up was handled was unclear in 37 studies (19%); the most commonly used method was survival analysis (66, 35%). When we varied assumptions about loss to follow-up, results of 19% of trials were no longer significant if we assumed no participants lost to follow-up had the event of interest, 17% if we assumed that all participants lost to follow-up had the event, and 58% if we assumed a worst case scenario (all participants lost to follow-up in the treatment group and none of those in the control group had the event). Under more plausible assumptions, in which the incidence of events in those lost to follow-up relative to those followed-up is higher in the intervention than control group, results of 0% to 33% trials were no longer significant.Conclusion Plausible assumptions regarding outcomes of patients lost to follow-up could change the interpretation of results of randomised controlled trials published in top medical journals.
Objective
To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock.
Design and setting
Post-hoc analysis of the multi-center double-blind ...randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST).
Patients and intervention
Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (0.01–0.03 U/min) or norepinephrine infusion (5–15 μg/min) in addition to open-label vasopressors and were included in the outcome analysis. All vasopressors were titrated and weaned to maintain a target blood pressure.
Measurement and results
RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine. In view of multiple simultaneous comparisons, a
p
value of 0.01 was considered statistically significant. Kidney injury was present in 464 patients (59.6%) at study entry. In patients in the RIFLE “Risk” category (
n
= 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal “Failure” or “Loss” categories (20.8 vs. 39.6%, respectively,
p
= 0.03), and a lower rate of use of renal replacement therapy (17.0 vs. 37.7%,
p
= 0.02). Mortality rates in the “Risk” category patients treated with vasopressin compared to norepinephrine were 30.8 versus 54.7%,
p
= 0.01, but this did not reach significance in a multiple logistic regression analysis (OR = 0.33, 99% CI 0.10–1.09,
p
= 0.02). The interaction of treatment group and RIFLE category was significant in predicting mortality.
Conclusions
Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.
Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as ...compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors.
In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions.
A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10).
Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 controlled-trials.com.).
PDF
