Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size.
To evaluate risk ...factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization.
A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form SF-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status.
At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes.
Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes.
Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.
To evaluate the ...association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.
Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight PBW) and daily assessment of other mortality predictors.
An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval CI, 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier.
Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).
Myeloid malignancies, including acute myeloid leukaemia (AML), arise from the expansion of haematopoietic stem and progenitor cells that acquire somatic mutations. Bulk molecular profiling has ...suggested that mutations are acquired in a stepwise fashion: mutant genes with high variant allele frequencies appear early in leukaemogenesis, and mutations with lower variant allele frequencies are thought to be acquired later
. Although bulk sequencing can provide information about leukaemia biology and prognosis, it cannot distinguish which mutations occur in the same clone(s), accurately measure clonal complexity, or definitively elucidate the order of mutations. To delineate the clonal framework of myeloid malignancies, we performed single-cell mutational profiling on 146 samples from 123 patients. Here we show that AML is dominated by a small number of clones, which frequently harbour co-occurring mutations in epigenetic regulators. Conversely, mutations in signalling genes often occur more than once in distinct subclones, consistent with increasing clonal diversity. We mapped clonal trajectories for each sample and uncovered combinations of mutations that synergized to promote clonal expansion and dominance. Finally, we combined protein expression with mutational analysis to map somatic genotype and clonal architecture with immunophenotype. Our findings provide insights into the pathogenesis of myeloid transformation and how clonal complexity evolves with disease progression.
Nearly 60% of patients who are intubated in intensive care units (ICUs) experience dysphagia after extubation, and approximately 50% of them aspirate. Little is known about dysphagia recovery time ...after patients are discharged from the hospital.
To determine factors associated with recovery from dysphagia symptoms after hospital discharge for acute respiratory distress syndrome (ARDS) survivors who received oral intubation with mechanical ventilation.
This is a prospective, 5-year longitudinal cohort study involving 13 ICUs at four teaching hospitals in Baltimore, Maryland. The Sydney Swallowing Questionnaire (SSQ), a 17-item visual analog scale (range, 0-1,700), was used to quantify patient-perceived dysphagia symptoms at hospital discharge, and at 3, 6, 12, 24, 36, 48, and 60 months after ARDS. An SSQ score greater than or equal to 200 was used to indicate clinically important dysphagia symptoms at the time of hospital discharge. Recovery was defined as an SSQ score less than 200, with a decrease from hospital discharge greater than or equal to 119, the reliable change index for SSQ score. Fine and Gray proportional subdistribution hazards regression analysis was used to evaluate patient and ICU variables associated with time to recovery accounting for the competing risk of death.
Thirty-seven (32%) of 115 patients had an SSQ score greater than or equal to 200 at hospital discharge; 3 died before recovery. All 34 remaining survivors recovered from dysphagia symptoms by 5-year follow-up, 7 (23%) after 6 months. ICU length of stay was independently associated with time to recovery, with a hazard ratio (95% confidence interval) of 0.96 (0.93-1.00) per day.
One-third of orally intubated ARDS survivors have dysphagia symptoms that persist beyond hospital discharge. Patients with a longer ICU length of stay have slower recovery from dysphagia symptoms and should be carefully considered for swallowing assessment to help prevent complications related to dysphagia.
Delayed return to work is common after acute respiratory distress syndrome (ARDS), but has undergone little detailed evaluation. We examined factors associated with the timing of return to work after ...ARDS, along with lost earnings and shifts in healthcare coverage.
Five-year, multisite prospective, longitudinal cohort study of 138 2-year ARDS survivors hospitalised between 2004 and 2007. Employment and healthcare coverage were collected via structured interview. Predictors of time to return to work were evaluated using Fine and Grey regression analysis. Lost earnings were estimated using Bureau of Labor Statistics data.
Sixty-seven (49%) of the 138 2-year survivors were employed prior to ARDS. Among 64 5-year survivors, 20 (31%)
returned to work across 5-year follow-up. Predictors of delayed return to work (HR (95% CI)) included baseline Charlson Comorbidity Index (0.77 (0.59 to 0.99) per point; p=0.04), mechanical ventilation duration (0.67 (0.55 to 0.82) per day up to 5 days; p<0.001) and discharge to a healthcare facility (0.49 (0.26 to 0.93); p=0.03). Forty-nine of 64 (77%) 5-year survivors incurred lost earnings, with average (SD) losses ranging from US$38 354 (21,533) to US$43 510 (25,753) per person per year. Jobless, non-retired survivors experienced a 33% decrease in private health insurance and concomitant 37% rise in government-funded coverage.
Across 5-year follow-up, nearly one-third of previously employed ARDS survivors never returned to work. Delayed return to work was associated with patient-related and intensive care unit/hospital-related factors, substantial lost earnings and a marked rise in government-funded healthcare coverage. These important consequences emphasise the need to design and evaluate vocation-based interventions to assist ARDS survivors return to work.
This ex vivo study aimed to evaluate the shaping abilities and preservation of dentin with traditional and modern instruments after using sizes 25 and 40 in oval canals of mandibular incisors with ...conservative access.
Thirty mandibular incisors with single straight oval canals were selected and assigned into 2 groups (n = 15) according to the instrument system used during preparation, Slim Shaper (SS) plus Apical Shaper (AS) and Protaper Gold (PG). The samples were subjected to micro-computed tomography before and after preparation with sizes 25 and 40. The shaping parameters evaluated included canal volume and surface area, amount of unprepared root canal walls, and reduction in pericervical dentin.
Canal volume and surface area were significantly increased after enlargement with each instrument size (P < .01). The percentage of unprepared areas showed a significant intragroup decrease after using PG F2 and F4 or SS 3 and AS (P < .05). Intergroup comparison showed no significant differences. Pericervical dentin was reduced in all groups. The intragroup comparison only revealed a significant reduction (P < .01) between PG F2 and F4. In addition, a significant decrease in pericervical dentin (P < .05) was observed between PG F4 40/.06 and AS 40/.03. No significant differences were observed between PG F2 25/.08 and SS 3 25/.04.
Increasing the instrumentation size from 25 to 40 significantly reduces the percentage of unprepared areas regardless of the system used. In addition, using a modern system with a regressive taper allows the maintenance of pericervical dentin without compromising shaping efficacy in the apical third of the mandibular incisors with oval canals and conservative access.
Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge. Preclinical and observational studies suggest that ...the use of statins might reduce delirium in intensive care. We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a randomised controlled trial.
We did this ancillary study within the SAILS trial, a randomised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome. This study was done at 35 hospitals in the USA. Patients were randomly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin (40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care, study day 28, or death) or placebo. Patients and investigators were masked to treatment assignment. Delirium was assessed with the validated Confusion Assessment Method for intensive care. Cognitive function was assessed with tests for executive function, language, verbal reasoning and concept formation, and working, immediate, and delayed memory. We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1·5 SDs below norms. The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months. This trial is registered with ClinicalTrials.gov (NCT00979121 and NCT00719446).
272 patients were assessed for delirium daily in intensive care. The mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (29%) in the placebo group; hazard ratio 1·14, 95% CI 0·92-1·41, p=0·22. At 6 months, 19 (36%) of 53 patients in the rosuvastatin group versus 29 (38%) of 77 in the placebo group had cognitive impairment, with no significant difference between groups (treatment effect 0·93, 95% CI 0·39-2·22; p=0·87). At 12 months, 20 (30%) of 67 patients versus 23 (28%) of 81 patients had cognitive impairment, with no significant difference between groups (treatment effect 1·1, 95% CI 0·5-2·6; p=0·82).
Most patients had delirium, with around a third of survivors having cognitive impairment over 1 year of follow-up. Despite encouraging preclinical and observational studies, this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority. Thus, there is continued need to evaluate interventions aimed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population.
National Heart, Lung and Blood Institute; Johns Hopkins Institute for Clinical and Translational Research; the SAILS trial was also supported by AstraZeneca.
To determine how the quality of life (QOL) of intensive care unit (ICU) survivors compares with the general population, changes over time, and is predicted by baseline characteristics.
Systematic ...literature review including MEDLINE, EMBASE, CINAHL and Cochrane Library. Eligible studies measured QOL > or = 30 days after ICU discharge using the Medical Outcomes Study 36-item Short Form (SF-36), EuroQol-5D, Sickness Impact Profile, or Nottingham Health Profile in representative populations of adult ICU survivors. Disease-specific studies were excluded.
Of 8,894 citations identified, 21 independent studies with 7,320 patients were reviewed. Three of three studies found that ICU survivors had significantly lower QOL prior to admission than did a matched general population. During post-discharge follow-up, ICU survivors had significantly lower QOL scores than the general population in each SF-36 domain (except bodily pain) in at least four of seven studies. Over 1-12 months of follow-up, at least two of four studies found clinically meaningful improvement in each SF-36 domain except mental health and general health perceptions. A majority of studies found that age and severity of illness predicted physical functioning.
Compared with the general population, ICU survivors report lower QOL prior to ICU admission. After hospital discharge, QOL in ICU survivors improves but remains lower than general population levels. Age and severity of illness are predictors of physical functioning. This systematic review provides a general understanding of QOL following critical illness and can serve as a standard of comparison for QOL studies in specific ICU subpopulations.
To summarize long-term quality of life (QOL) and the degree of variation in QOL estimates across studies of acute respiratory distress (ARDS) survivors.
A systematic review of studies evaluating QOL ...in ARDS survivors was conducted. Medline, EMBASE, CINAHL, pre-CINAHL, and the Cochrane Library were searched, and reference lists from relevant articles were evaluated. Two authors independently selected studies reporting QOL in adult survivors of ARDS or acute lung injury at least 30 days after intensive care unit discharge and extracted data on study design, patient characteristics, methods, and results.
Thirteen independent observational studies (557 patients) met inclusion criteria. Eight of these studies used eight different QOL instruments, allowing only qualitative synthesis of results. The five remaining studies (330 patients) measured QOL using the Medical Outcomes Study 36-Item Short Form survey (SF-36). Mean QOL scores were similar across these studies, falling within a range of 20 points for all domains. Pooled domain-specific QOL scores in ARDS survivors 6 months or later after discharge ranged from 45 (role physical) to 66 (social functioning), or 15-26 points lower than population norms, in all domains except mental health (11 points) and role physical (39 points). Corresponding confidence intervals were no wider than +/-9 points. Six studies all found stable or improved QOL over time, but only one found significant improvement beyond 6 months after discharge.
ARDS survivors in different clinical settings experience similar decrements in QOL. The precise magnitude of these decrements helps clarify the long-term prognosis for ARDS survivors.
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