The impact of frailty on intensive care unit outcomes: a systematic review and meta-analysis

Purpose

Functional status and chronic health status are important baseline characteristics of critically ill patients. The assessment of frailty on admission to the intensive care unit (ICU) may provide objective, prognostic information on baseline health. To determine the impact of frailty on the outcome of critically ill patients, we performed a systematic review and meta-analysis comparing clinical outcomes in frail and non-frail patients admitted to ICU.

Methods

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PubMed, CINAHL, and Clinicaltrials.gov. All study designs with the exception of narrative reviews, case reports, and editorials were included. Included studies assessed frailty in patients greater than 18 years of age admitted to an ICU and compared outcomes between fit and frail patients. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were hospital and long-term mortality. We also determined the prevalence of frailty, the impact on other patient-centered outcomes such as discharge disposition, and health service utilization such as length of stay.

Results

Ten observational studies enrolling a total of 3030 patients (927 frail and 2103 fit patients) were included. The overall quality of studies was moderate. Frailty was associated with higher hospital mortality [relative risk (RR) 1.71; 95% CI 1.43, 2.05; p < 0.00001; I ² = 32%] and long-term mortality (RR 1.53; 95% CI 1.40, 1.68; p < 0.00001; I ² = 0%). The pooled prevalence of frailty was 30% (95% CI 29–32%). Frail patients were less likely to be discharged home than fit patients (RR 0.59; 95% CI 0.49, 0.71; p < 0.00001; I ² = 12%).

Conclusions

Frailty is common in patients admitted to ICU and is associated with worsened outcomes. Identification of this previously unrecognized and vulnerable ICU population should act as the impetus for investigating and implementing appropriate care plans for critically ill frail patients. Registration: PROSPERO (ID: CRD42016053910).

     

Evaluation of the impact of computed high <Emphasis Type="Italic">b</Emphasis>-value diffusion-weighted imaging on prostate cancer detection

Purpose

The purpose of this study was to compare high b-value (b = 2000 s/mm²) acquired diffusion-weighted imaging (aDWI) with computed DWI (cDWI) obtained using four diffusion models—mono-exponential (ME), intra-voxel incoherent motion (IVIM), stretched exponential (SE), and diffusional kurtosis (DK)—with respect to lesion visibility, conspicuity, contrast, and ability to predict significant prostate cancer (PCa).

Methods

Ninety four patients underwent 3 T MRI including acquisition of b = 2000 s/mm² aDWI and low b-value DWI. High b = 2000 s/mm² cDWI was obtained using ME, IVIM, SE, and DK models. All images were scored on quality independently by three radiologists. Lesions were identified on all images and graded for lesion conspicuity. For a subset of lesions for which pathological truth was established, lesion-to-background contrast ratios (LBCRs) were computed and binomial generalized linear mixed model analysis was conducted to compare clinically significant PCa predictive capabilities of all DWI.

Results

For all readers and all models, cDWI demonstrated higher ratings for image quality and lesion conspicuity than aDWI except DK (p < 0.001). The LBCRs of ME, IVIM, and SE were significantly higher than LBCR of aDWI (p < 0.001). Receiver Operating Characteristic curves obtained from binomial generalized linear mixed model analysis demonstrated higher Area Under the Curves for ME, SE, IVIM, and aDWI compared to DK or PSAD alone in predicting significant PCa.

Conclusion

High b-value cDWI using ME, IVIM, and SE diffusion models provide better image quality, lesion conspicuity, and increased LBCR than high b-value aDWI. Using cDWI can potentially provide comparable sensitivity and specificity for detecting significant PCa as high b-value aDWI without increased scan times and image degradation artifacts.

     

A multicenter multinational study of abdominal candidiasis: epidemiology,outcomes and predictors of mortality

Purpose

Clinical data on patients with intra-abdominal candidiasis (IAC) is still scarce.

Methods

We collected data from 13 hospitals in Italy, Spain, Brazil, and Greece over a 3-year period (2011–2013) including patients from ICU, medical, and surgical wards.

Results

A total of 481 patients were included in the study. Of these, 27 % were hospitalized in ICU. Mean age was 63 years and 57 % of patients were male. IAC mainly consisted of secondary peritonitis (41 %) and abdominal abscesses (30 %); 68 (14 %) cases were also candidemic and 331 (69 %) had concomitant bacterial infections. The most commonly isolated Candida species were C. albicans (n = 308 isolates, 64 %) and C. glabrata (n = 76, 16 %). Antifungal treatment included echinocandins (64 %), azoles (32 %), and amphotericin B (4 %). Septic shock was documented in 40.5 % of patients. Overall 30-day hospital mortality was 27 % with 38.9 % mortality in ICU. Multivariate logistic regression showed that age (OR 1.05, 95 % CI 1.03–1.07, P < 0.001), increments in 1-point APACHE II scores (OR 1.05, 95 % CI 1.01–1.08, P = 0.028), secondary peritonitis (OR 1.72, 95 % CI 1.02–2.89, P = 0.019), septic shock (OR 3.29, 95 % CI 1.88–5.86, P < 0.001), and absence of adequate abdominal source control (OR 3.35, 95 % CI 2.01–5.63, P < 0.001) were associated with mortality. In patients with septic shock, absence of source control correlated with mortality rates above 60 % irrespective of administration of an adequate antifungal therapy.

Conclusions

Low percentages of concomitant candidemia and high mortality rates are documented in IAC. In patients presenting with septic shock, source control is fundamental.

     

Can diffusion-weighted magnetic resonance imaging predict tumor recurrence of uterine cervical cancer after concurrent chemoradiotherapy?

Purpose

To retrospectively investigate the utility of diffusion-weighted imaging (DWI) for predicting clinical outcome after concurrent chemoradiotherapy (CCRT) in uterine cervical cancer.

Materials and methods

Seventy-four consecutive patients with biopsy-proven cervical cancer who received CCRT underwent DWI at 3T. All patients had MR examinations before therapy (preTx) and at 4 weeks of initiating therapy (midTx). At each point, ADC (apparent diffusion coefficient) was measured in the tumors and ADC change between preTx and midTx were also calculated. For predicting tumor recurrence, MR variables and clinical variables were evaluated and the results were compared.

Results

During a mean follow-up of 32.1 months, tumor recurrence developed in 15 (20%) patients: local recurrence (n = 7), distant metastasis (n = 5), and both (n = 3). MidTx tumor ADCs and tumor ADC changes between preTx and midTx were significantly different between the recurrence and non-recurrence groups (P < 0.05), while preTx tumor ADCs were not significantly different between the groups (P = 0.892). Univariate analysis revealed that histologic type, stage, preTx tumor size and volume, and tumor ADC change were significantly related to tumor recurrence (all P < 0.05). However, on multivariate analysis, tumor ADC changes [hazard ratio (HR) 0.886; 95% confidence interval (CI) 0.836–0.940; P = 0.001] and histological type (HR 6.063; 95% CI 1.404–26.187; P = 0.016) were the significant independent predictors of tumor recurrence.

Conclusion

Tumor ADC changes between preTx and midTx might be a useful biomarker for the prediction of cervical cancer recurrence after CCRT.

     

Quality indicators of continuous renal replacement therapy (CRRT) care in critically ill patients: a systematic review

Objectives

Renal replacement therapy is increasingly utilized in the intensive care unit (ICU), of which continuous renal replacement therapy (CRRT) is most common. Despite CRRT being a relatively invasive and resource intensive technology, there remains wide practice variation in its application. This systematic review appraised the evidence for quality indicators (QIs) of CRRT care in critically ill patients.

Design

A comprehensive search strategy was developed and performed in five citation databases (Medline, Embase, CINAHL, Cochrane Library, and PubMed) and select grey literature sources. Two reviewers independently screened, selected, and extracted data using standardized forms. Each retrieved citation was appraised for quality using the Newcastle–Ottawa Scale (NOS) and Cochrane risk of bias tool. Data were summarized narratively.

Measurements and main results

Our search yielded 8374 citations, of which 133 fulfilled eligibility. This included 97 cohort studies, 24 randomized controlled trials, 10 case-control studies, and 2 retrospective medical audits. The quality of retrieved studies was generally good. In total, 18 QIs were identified that were mentioned in 238 instances. Identified QIs were classified as related to structure (n = 4, 22.2 %), care processes (n = 9, 50.0 %), and outcomes (n = 5, 27.8 %). The most commonly mentioned QIs focused on filter lifespan (n = 98), small solute clearance (n = 46), bleeding (n = 30), delivered dose (n = 19), and treatment interruption (n = 5). Across studies, the definitions used for QIs evaluating similar constructs varied considerably. When identified, QIs were most commonly described as important (n = 144, 48.3 %), scientifically acceptable (n = 32, 10.7 %), and useable and/or feasible (n = 17, 5.7 %) by their primary study authors.

Conclusions

We identified numerous potential QIs of CRRT care, characterized by heterogeneous definitions, varying quality of derivation, and limited evaluation. Further study is needed to prioritize a concise inventory of QIs to measure, improve, and benchmark CRRT care for critically ill patients.

Systematic review registration

PROSPERO CRD42015015530.

     

A recovery program to improve quality of life,sense of coherence and psychological health in ICU survivors: a multicenter randomized controlled trial,the RAPIT study

Purpose

The aim of this randomized controlled trial (RCT) was to test the effectiveness of a post-ICU recovery program compared to standard care during the first year after ICU discharge.

Methods

A pragmatic, non-blinded, multicenter, parallel-group RCT was conducted between December 2012 and December 2015, at ten intensive care units (ICUs) in Denmark. We randomly assigned 386 adult patients (≥18 years) after receiving mechanical ventilation (≥48 h) to standard care (SC) plus a nurse-led intensive care recovery program or standard care alone after ICU discharge (190 intervention, 196 SC). Primary outcome was health-related quality of life (HRQOL) at 12 months. Secondary outcomes were sense of coherence (SOC), anxiety, depression, and post-traumatic stress disorder (PTSD) assessed at 3 and 12 months after ICU discharge including utilization of healthcare services at 12 months.

Results

At 12 months, we found no differences in HRQOL between groups (mean difference in the Physical Component Summary score, 1.41 [95 % CI, ?1.53 to 4.35; p = 0.35] (n = 235); and in the Mental Component Summary score, 1.92 [95 % CI, ?1.06 to 4.90; p = 0.11] (n = 235). No differences were found on self-reported SOC (p = 0.63), anxiety (p = 0.68), depression (p = 0.67), PTSD (p = 0.27), or the utilization of healthcare services including rehabilitation. We found a difference on anxiety, when a cut-off point ≥11 was applied, in per protocol analysis of complete cases at 3 months favoring the intervention (8.8 % vs. 16.2 %, p = 0.04).

Conclusions

The tested recovery program was not superior to standard care during the first 12 months post-ICU.

Trial registration

The trial is registered at Clinicaltrials.gov, identification no. NCT01721239.

     

Early goal-directed nutrition versus standard of care in adult intensive care patients: the single-centre,randomised, outcome assessor-blinded EAT-ICU trial

Purpose

We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients.

Methods

We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders.

Results

We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI ?5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days.

Conclusions

EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients. Clinicaltrials.gov identifier no. NCT01372176.

     

Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

Purpose

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.

Methods

Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.

Results

Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10^?4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10^?3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10^?5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10^?3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10^?3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10^?3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313).

Conclusions

Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

     

Factors and Regional Differences Associated with Endometriosis: A Multi-Country,Case–Control Study

Introduction

The present study aimed to investigate clinical, lifestyle, and environmental factors associated with endometrioma (OMA) and/or deep infiltrating endometriosis (DIE) as determined by case–control comparison [women with superficial peritoneal endometriosis (SUP) or no endometriosis], and compare differences between factor associated with endometriosis at a national level.

Methods

This was three countries (China, Russia, and France), case–control study in 1008 patients. Patients were identified and enrolled during their first routine appointment with their physician post-surgery for a benign gynecologic indication, excluding pregnancy. Retrospective information on symptoms and previous medical history was collected via face-to-face interviews; patients also completed a questionnaire to provide information on current habits. For every DIE patient recruited (n = 143), two women without endometriosis (n = 288), two SUP patients (n = 288), and two OMA patients (n = 288) were recruited.

Results

For the overall population, factors significantly associated (P ≤ 0.05) with DIE or OMA [Odds ratio (OR) >1] were: previous use of hormonal treatment for endometriosis [OR 6.66; 95% confidence interval (CI) 4.05–10.93]; previous surgery for endometriosis (OR 1.95; 95% CI 1.11–3.43); and living or working in a city or by a busy area (OR 1.66; 95% CI 1.09–2.52). Differences between regions with regard to the diagnosis, symptomatology, and treatment of endometriosis exist.

Conclusion

The findings provide insight into potential risk factors for endometriosis and differences between regions in terms of endometriosis management and symptomatology. Further investigations are required to confirm the associations found in this study.

Trial registration

ClinicalTrials.gov identifier, NCT01351051.

Funding

Ipsen.

     

Small volume resuscitation with 20% albumin in intensive care: physiological effects

Purpose

We set out to assess the resuscitation fluid requirements and physiological and clinical responses of intensive care unit (ICU) patients resuscitated with 20% albumin versus 4–5% albumin.

Methods

We performed a randomised controlled trial in 321 adult patients requiring fluid resuscitation within 48 h of admission to three ICUs in Australia and the UK.

Results

The cumulative volume of resuscitation fluid at 48 h (primary outcome) was lower in the 20% albumin group than in the 4–5% albumin group [median difference ??600 ml, 95% confidence interval (CI) ??800 to ??400; P?<?0.001]. The 20% albumin group had lower cumulative fluid balance at 48 h (mean difference ??576 ml, 95% CI ??1033 to ??119; P?=?0.01). Peak albumin levels were higher but sodium and chloride levels lower in the 20% albumin group. Median (interquartile range) duration of mechanical ventilation was 12.0 h (7.6, 33.1) in the 20% albumin group and 15.3 h (7.7, 58.1) in the 4–5% albumin group (P?=?0.13); the proportion of patients commenced on renal replacement therapy after randomization was 3.3% and 4.2% (P?=?0.67), respectively, and the proportion discharged alive from ICU was 97.4% and 91.1% (P?=?0.02).

Conclusions

Resuscitation with 20% albumin decreased resuscitation fluid requirements, minimized positive early fluid balance and was not associated with any evidence of harm compared with 4–5% albumin. These findings support the safety of further exploration of resuscitation with 20% albumin in larger randomised trials.

Trial registration

http://www.anzctr.org.au. Identifier ACTRN12615000349549.

     

Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective,two-centre,open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis

Purpose

This study aims to determine if continuous infusion (CI) is associated with better clinical and pharmacokinetic/pharmacodynamic (PK/PD) outcomes compared to intermittent bolus (IB) dosing in critically ill patients with severe sepsis.

Methods

This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.

Results

A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p < 0.043) than IB participants. PK/PD target attainment rates were higher in the CI arm at 100 % fT _>MIC than the IB arm on day 1 (97 versus 70 %, p < 0.001) and day 3 (97 versus 68 %, p < 0.001) post-randomisation. There was no difference in 14-day or 30-day survival between the treatment arms.

Conclusions

In critically ill patients with severe sepsis not receiving RRT, CI demonstrated higher clinical cure rates and had better PK/PD target attainment compared to IB dosing of beta-lactam antibiotics. Continuous beta-lactam infusion may be mostly advantageous for critically ill patients with high levels of illness severity and not receiving RRT. Malaysian National Medical Research Register ID: NMRR-12-1013-14017.

     

Extracorporeal life support during cardiac arrest and cardiogenic shock: a systematic review and meta-analysis

Purpose

Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction.

Methods

We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (n = 3098) and four included patients with cardiogenic shock after acute myocardial infarction (n = 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the I ² statistic.

Results

In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used [95 % CI 6–20 %; p < 0.001; number needed to treat (NNT) 7.7] and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7–20 %; p < 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14–52 %; p < 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (?3 %; 95 % CI ?21 to 14 %; p = 0.70; NNH 33).

Conclusions

In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP.

     

Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases

Purpose

To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications.

Methods

During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications.

Results

Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient.

Conclusions

Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.

     

Early-stage clear cell tubulopapillary renal cell carcinoma: imaging features and distinction from clear cell and papillary subtypes

Purpose

Clear cell tubulopapillary renal cell carcinoma (CCTPRCC) is a recently described, low-grade subtype of renal cancer. We determined if imaging features could be used to distinguish early-stage CCTPRCC from stage-matched clear cell RCC (ccRCC) and papillary RCC (pRCC).

Methods

This IRB-approved retrospective study included 54 stage T1a patients with pathologically confirmed CCTPRCC (n = 18), ccRCC (n = 18), and pRCC (n = 18). CT (n = 48) and MRI (n = 27) exams were reviewed and imaging features compared. Continuous variables were evaluated using ANOVA and Tukey’s multiple comparison tests. Categorical variables were compared using Chi-square test or Fisher’s exact test.

Results

Compared to pRCC, CCTPRCC had a lower mean attenuation value on unenhanced CT (p < 0.017), was more often hyperintense on T2-weighted images (p < 0.0001), showed an ill-defined margin (p = 0.003), and demonstrated nonenhancing areas (p = 0.0003). The presence of all three of these statistically significant features [hypoattenuation (unenhanced attenuation ≤25 HU), ill-defined margin, nonenhancing areas] yielded an area under the receiver operator curve (ROC) of 0.92 (95% CI 0.83–0.99) for differentiating CCTPRCC from pRCC. There were no significant differences in the imaging features of CCTPRCC and ccRCC.

Conclusions

Early-stage clear cell tubulopapillary renal cell carcinoma can be distinguished from papillary RCC based on low attenuation on unenhanced CT, high intensity on T2-weighted images, an ill-defined margin, and presence of nonenhancing areas, but cannot be distinguished from clear cell RCC.

     

Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER)

Purpose

Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.

Methods

A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852).

Results

Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2–6) versus 4 days (IQR 2–7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59–14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07–13.31); p = 0.04].

Conclusions

Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.

     

Quantitative assessment of muscle stiffness with acoustic radiation force impulse elastography after botulinum toxin A injection in children with cerebral palsy

Purpose

Our objective in this study was to assess the changes in medial gastrocnemius muscle (GCM) stiffness after botulinum toxin A (BTA) injection in children with cerebral palsy (CP) by using acoustic radiation force impulse (ARFI) elastography and to research the usability of this technique in clinical practice.

Materials and methods

Twenty-four spastic lower extremities of 12 children with CP were assessed. BTA injection treatment was applied to the medial GCM. Muscle stiffness was measured with the ARFI technique before the procedure and a month after the procedure. The patients were assessed with the modified Ashworth scale (MAS) in the physiotherapy department at about the same time. Shear wave velocity (SWV) values and MAS scores before and after the treatment were compared.

Results

Mean SWV values were measured as 3.20 ± 0.14 m/s before BTA and as 2.45 ± 0.21 m/s after BTA, and the difference between them was found to be statistically significant (p < 0.001). Mean MAS score (2.33 ± 0.70) after BTA decreased significantly when compared to the score before BTA (2.96 ± 0.62) (p = 0.001). SWV values positively correlated with MAS scores (ρ = 0.578, p = 0.003). The interobserver agreement expressed as interclass correlation coefficient (ICC) was 0.65 (95% CI 0.33–0.84, p < 0.001).

Conclusion

ARFI elastography for identifying structural changes that occur in the spastic muscle after BTA injection in children with CP can yield more valuable information with combined use of MAS.

     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Prognostic value of chromogranin A in severe sepsis: data from the FINNSEPSIS study

Purpose

To assess the prognostic information of chromogranin A (CgA), a marker associated with adrenergic tone and myocardial function, in patients with severe sepsis.

Methods

CgA levels were measured at the time of study inclusion and 72 h later in 232 patients with severe sepsis recruited from 24 ICUs in Finland (FINNSEPSIS study).

Results

Sixty-five patients (28 %) died during the index hospitalization. CgA levels at inclusion and after 72 h correlated with several established indices of risk in sepsis. Patients who died during the hospitalization had higher baseline CgA levels than hospital survivors: 14.0 (Q1–3, 7.4–27.4) versus 9.1 (5.9–15.8) nmol/l, P = 0.002, and after 72 h: 16.2 (9.0–31.1) versus 9.8 (6.0–18.0) nmol/l, P = 0.001. Prior cardiovascular disease (P = 0.04) and cardiovascular SOFA levels on day 3 (P = 0.03) were associated with higher CgA levels after 72 h by linear regression. CgA levels on study inclusion and after 72 h were independently associated with hospital mortality by logistic regression: OR (logarithmically transformed CgA levels) 1.95 (95 % CI 1.01–3.77), P = 0.046 and OR 2.03 (95 % CI 1.18–3.49), P = 0.01, respectively. The prognostic accuracy was comparable for CgA measurements and SAPS II score, and the addition of CgA measurements to the SAPS II score improved risk stratification of the patients as assessed by the category-free net reclassification index. A CgA level >6.6 nmol/l on study inclusion was associated with septic shock during the hospitalization.

Conclusion

CgA levels measured during hospitalization for severe sepsis are associated with cardiovascular dysfunction and may provide additional prognostic information in patients with severe sepsis.

     

Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis

Purpose

Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock.

Methods

We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, “Igaku Chuo Zasshi”, the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used.

Results

Six trials (857 participants; weighted mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78–1.36; I ² = 25%; n = 797]. The pooled RR for adverse events was 2.17 (95% CI 0.68–6.94; I ² = 0%; n = 717). Organ dysfunction scores over 24–72 h after PMX-HP treatment did not change significantly (standardized mean difference ? 0.26; 95% CI ? 0.64 to 0.12; I ² = 78%; n = 797). The certainty of the body of evidence was judged as low for both benefit and harm using the GRADE methodology.

Conclusions

There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock.

Registration

PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356).

     

Outcome and late effects among acute myeloid leukemia survivors: a nationwide population-based study

Background

Understanding of pathogenesis and treatment for acute myeloid leukemia (AML) is growing. However, studies regarding the outcomes and late effects among AML survivors are relatively limited.

Methods

This nationwide population-based study used medical records from the Taiwanese National Health Insurance Research Database. A total of 3356 AML patients diagnosed from 2000 to 2008 were analyzed. The physiological and psychological morbidities in AML survivors were compared to those identified from a normal population. This study also compared late effects among AML survivors treated by intensive chemotherapy alone and allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Results

The incidence of AML in Taiwan has increased from 1.07 per 100,000 persons in 2000 to 2.17 per 100,000 persons in 2008 (p < 0.0001). With the median overall survival (OS) time of 0.98 years, 25.0 % of AML patients in this study cohort received best supportive care alone. Compared to the normal population, AML survivors had higher rates of hypertension (hazard ratio [HR] 1.69; 95 % confidence interval [CI] 1.18–2.42; p < 0.01), cardiovascular disease (HR 2.53; 95 % CI 1.39–4.61; p < 0.01), diabetes (HR 2.27; 95 % CI 1.48–3.48; p < 0.001), and psychological disorders (HR 1.45; 95 % CI 1.04–2.04; p < 0.05). Although patients undergoing allo-HSCT had a better OS than did patients treated with intensive chemotherapy alone (median not reached vs. 1.53 years; p < 0.0001), diabetes was found more often among allo-HSCT recipients than among patients receiving intensive chemotherapy only (HR 2.93; 95 % CI 1.21–7.08; p < 0.05).

Conclusion

Regular physical and psychological surveillance of AML survivors is needed especially for those receiving allo-HSCT.