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.

     

The usefulness of a computer-aided diagnosis scheme for improving the performance of clinicians to diagnose non-mass lesions on breast ultrasonographic images

Purpose

The purpose of this study was to evaluate the usefulness of a computer-aided diagnosis (CAD) scheme for improving the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images.

Methods

The database included 97 ultrasonographic images with hypoechoic areas: 48 benign cases [benign lesion with benign mammary tissue or fibrocystic disease (n = 20), fibroadenoma (n = 11), and intraductal papilloma (n = 17)] and 49 malignant cases [ductal carcinoma in situ (n = 17) and invasive ductal carcinoma (n = 32)]. Seven clinicians, three expert breast surgeons, and four general surgeons participated in the observer study. They were asked their confidence level concerning the possibility of malignancy in all 97 cases with and without the use of the CAD scheme. Receiver operating characteristic (ROC) analysis was performed to evaluate the usefulness of the CAD scheme.

Results

The areas under the ROC curve (AUC) improved for all observers when they used the CAD scheme and increased from 0.649 to 0.783 (P = 0.0167). Notably, the AUC for the general surgeon group increased from 0.625 to 0.793 (P = 0.045).

Conclusions

This study showed that the performance of clinicians to diagnose non-mass lesions appearing as hypoechoic areas on breast ultrasonographic images was improved by the use of a CAD scheme.

     

Diffusion-weighted imaging of hepatocellular carcinomas: a retrospective analysis of correlation between apparent diffusion coefficients and histological grade

Purpose

To define correlations between the pathological grades of hepatocellular carcinomas (HCCs) and apparent diffusion coefficients (ADCs) derived using breath-holding diffusion-weighted imaging (BH-DWI).

Methods

We retrospectively evaluated 94 patients (105 lesions) with pathologically proved HCC who underwent hepatic DWI on a 3.0-T MR platform. HCCs were divided into five groups: well-differentiated (n = 10), well-to-moderately differentiated (n = 11), moderately differentiated (n = 51), moderately to poorly differentiated (n = 20), and poorly differentiated (n = 13) groups. The ADCs of carcinomas across different histological grades were compared by one-way analysis of variance. Spearman’s rank correlation test was used to analyze correlations between the degree of histopathological differentiation and ADC. Results were corrected for multiple comparisons using the Bonferroni correction.

Results

The BH technique yielded ADC values that differed significantly by the extent of differentiation (F = 8.392, p < 0.001). A significant negative correlation was found between the extent of differentiation and ADCs (r = ?0.462, p < 0.001). The mean ADC values of poorly differentiated HCCs were significantly lower than the well-, well-to-moderately, moderately, and moderately to poorly differentiated HCCs (p values were <0.001, <0.001, 0.003, and 0.031, respectively).

Conclusion

ADC values obtained with BH-DWI may be of importance to non-invasively predict HCC tumor differentiation, and the extent of histological HCC differentiation was inversely correlated with ADC values.

     

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.

     

Histogram analysis of noncancerous liver parenchyma on gadoxetic acid-enhanced MRI: predictive value for liver function and pathology

Purpose

To clarify whether the heterogeneity of hepatic parenchyma in the hepatobiliary phase on gadoxetic acid-magnetic resonance (MR) imaging is correlated with liver damage.

Materials and methods

We retrospectively examined the cases of 98 patients with or without chronic liver disease who underwent gadoxetic acid-enhanced 3T MR imaging before a hepatectomy between December 2010 and October 2014. For the evaluation of the heterogeneity of the signal intensity in the hepatobiliary phase, we placed the region of interest on the hepatic parenchyma, and the skewness and kurtosis were calculated using ImageJ software. A discriminant analysis was performed to examine the routine preoperative laboratory test results including indocyanine green retention at 15 min (ICG-R15), necro-inflammation grade, and liver fibrosis stage according to the METAVIR system: A0/1 (n = 69) and A2 (n = 29); F0/1 (n = 47), F2/3 (n = 31), and F4 (n = 20).

Results

The combination of skewness and kurtosis could discriminate the high ICG-R15 (>20) and low (<20) groups (lambda; 0.925, p = 0.025), necro-inflammatory grade (lambda; 0.926, p = 0.026), and fibrosis stage (lambda; 0.752, p < 0.0001) with statistical significance. The difference between the patients with normal values and those with an abnormal platelet count or aspartate transaminase level was also detectable (lambda; 0.901, p < 0.007, and lambda; 0.864, p = 0.001, respectively).

Conclusion

Histogram analyses of the hepatobiliary phase of gadoxetic acid-enhanced MR imaging have potential as a biomarker for the assessment of liver function, liver fibrosis, and necro-inflammation.

     

Prevalence of benign focal liver lesions: ultrasound investigation of 45,319 hospital patients

Purpose

The aim of the study was to determine the sonographic prevalence of benign focal liver lesions on the basis of a population of hospital patients.

Methods

The ultrasound results in a population of (n = 45,319) hospital patients over a period of 10 years were examined retrospectively and evaluated for the diagnosis of benign focal liver lesions [hepatic cysts, hepatic hemangioma, focal nodular hyperplasia (FNH), hepatic adenoma, and focal fatty sparing]. Results that were incomplete or ambiguous were excluded from this study.

Results

At least one of the lesions to be investigated was diagnosed in 15.1% (n = 6839) of the patients of the total population. The most commonly recorded lesion, with a total prevalence of 6.3% (n = 2839), was focal fatty sparing, followed by hepatic cysts with 5.8% (n = 2631). The prevalence of hepatic hemangioma was 3.3% (n = 1640), while that of FNH was 0.2% (n = 81) and that of hepatic adenoma was 0.04% (n = 19). An association between the occurrence of benign focal liver lesions and age was observed.

Conclusions

The calculated prevalence of benign focal liver lesions shows that on the fortuitous discovery of space-occupying lesions of the liver, first consideration should be given to focal fatty sparing, simple hepatic cysts and hemangiomas. The finding of a FNH or an adenoma is rarely a random discovery.

     

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.

     

Prevalence of hepatic lesion types defined by T2-weighted and dynamic gadolinium-enhanced MR imaging in patients with metastasized neuroendocrine tumors

Purpose

Identifying liver metastases from neuroendocrine tumors (NETs) is a pretherapeutic challenge in patients who are candidates for liver resection. The aims of our study are to characterize and determine the frequency of different MRI characteristics of liver metastases caused by NETs in a lesion-by-lesion analysis and to determine the frequency of monomorphous and polymorphous metastases in a patient-by-patient analysis.

Methods

This retrospective study involved 47 patients with liver metastases arising from histologically confirmed NETs. In a lesion-by-lesion analysis, we classified these metastases according to their MRI characteristics as follows: hypervascular lesions with homogeneous or peripheral enhancement, hypovascular lesions, pure cystic lesions, and mixed solid/cystic lesions. In the patient-by-patient analysis, we distinguished patients whose metastases had the same MRI characteristics from patients with mixed lesion characteristics.

Results

A total of 376 metastases were analyzed. Of these, 84.3% (n = 317) were hypervascular, with 51.9% showing homogeneous enhancement and 32.4% (n = 122) showing peripheral enhancement. Another 7.4% (n = 28) were hypovascular, 5.3% (n = 20) were pure cystic, and 2.9% (n = 11) were mixed solid/cystic. After excluding three patients with solitary lesions, 40.9% of patients (n = 18) had mixed-type lesions, consisting of hypervascular lesions with either homogeneous or peripheral enhancement in 27.3% of cases (n = 12), while 59.1% of patients (n = 26) had identical lesions.

Conclusion

Approximately 15% of metastases have atypical MRI characteristics and are either hypovascular or cystic. Metastases with different MRI characteristics coexist in 40% of patients.

     

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.

     

Safety,efficacy, and patient-perceived satisfaction of peripherally inserted central catheters in terminally ill cancer patients: a prospective multicenter observational study

Purpose

The purpose of this study was to investigate the safety, efficacy, and subjective satisfaction of peripherally inserted central catheters (PICCs) in terminally ill cancer patients.

Methods

All PICCs were inserted by an interventional radiologist with radiological guidance. We monitored the occurrence of PICC-related complication and evaluated the patient-perceived satisfaction for PICC using semi-structured questionnaire.

Results

A total of 36 terminally ill cancer patients underwent PICC. Three patients had 2 PICC insertions; hence, finally 39 episodes during 829 PICC days were analyzed. All procedures were completed without any procedure-related complication. The median catheter life span was 19.0 days (95 % CI, 14.1–23.9). Thirty-four cases maintained the PICC until the intended time, while the other 5 cases (12.8 %; 6.1/1000 PICC days) were premature PICC removals. Totally 10 complications (25.6 %; 12.3/1000 PICC days) were reported including premature removals (n = 5), trivial bleedings (n = 3), and thrombophlebitis (n = 2). Patients reported that the procedure was not distressing (42 %), a little distressing (36 %), or distressing (21 %). Of 30 patients who had preserved cognitive function at fifth day, most patients (n = 25, 83 %) reported more comfort although the other 5 patients reported no change (n = 3) or less comfort (n = 2).

Conclusions

PICCs were safely inserted and showed favorable maintenance rate with acceptable complications. Additionally, most of the patients felt that parenteral access became much comfortable after PICC insertion. When considering the characteristics of terminally ill cancer patients, poor general condition and a limited period of survival, PICC could be a safe and effective method for intravenous access.

     

A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients

Introduction

Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions.

Methods

Data were obtained from the Optum Research Database. Patients were aged 18–63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated.

Results

Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66–79%) compared with 11–59% for all other biologics.

Conclusion

One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated.

Funding

Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).

     

Efficacy of the echo pattern classification of ovarian tumors 2000 in conjunction with transvaginal ultrasonography for diagnosis of ovarian masses

Purpose

Because of the need for rapid, accurate clinical differentiation between malignant and benign ovarian masses, we investigated the diagnostic efficacy of the echo pattern classification used together with transvaginal ultrasound.

Methods

We classified, on the basis of six echo pattern types, transvaginal ultrasound images of 405 ovarian masses treated surgically between January 2011 and December 2012. We compared the resulting classifications to the postoperative histopathologic diagnoses and computed the diagnostic sensitivity and specificity of the echo pattern-based classification for malignancy.

Results

Our review yielded the following echo patterns: type I, n = 61; type II; n = 154; type III, n = 82; type IV, n = 61; type V, n = 34; and type VI, n = 13. Histopathologically, there were 75 borderline malignant/malignant tumors and 330 benign tumors. Diagnostic sensitivity was 80.0 % and specificity was 85.5 % when echo types I–III were categorized as benign and types IV–VI were categorized as malignant. Further, with respect to benign tumors: sensitivity and specificity for chocolate cysts were 85.5 and 88.4 %, respectively, and for dermoid cysts were 67.2 and 97.9 %, respectively.

Conclusions

With the echo pattern classification, ovarian masses can be diagnosed easily and accurately upon transvaginal ultrasound.

     

Central vascular structures as a characteristic finding of regenerative nodules using hepatobiliary phase gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid-enhanced MRI and arterial dominant phase contrast-enhanced US

Objective

We investigated the characteristic findings of regenerative nodules (RNs) for differentiating early hepatocellular carcinoma (HCC) from high-grade dysplastic nodules (HGDNs) using magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA; EOB-MRI) and contrast-enhanced ultrasonography (CEUS) in patients with chronic liver disease.

Subjects and methods

Pathologically confirmed lesions (100 early HCCs, 7 HGDNs, and 20 RNs with a maximum diameter of more than 1 cm and mean maximal diameters of 15.5, 15.1, and 14.8 mm, respectively) were enrolled in this retrospective study. The signal intensities of these lesions during the hepatobiliary phase of EOB-MRI were investigated, and findings characteristic of RNs using this modality were also evaluated using CEUS.

Results

Ninety-eight of the 100 early HCCs that were hypo-intense (n = 95), iso-intense (n = 2), or hyper-intense (n = 1) and the seven HGDNs that were hypo-intense (n = 6) or hyper-intense (n = 1) during the hepatobiliary phase of EOB-MRI exhibited centripetal vessels during the arterial dominant phase of CEUS, although one early HCC that was hypo-intense exhibited both centrifugal and centripetal vessels. Eighteen of the 20 RNs and one early HCC that were hyper-intense with a small central hypo-intensity and the remaining two RNs that were hyper-intense on EOB-MRI exhibited centrifugal vessels during the arterial dominant phase of CEUS. The small central hypo-intense area corresponded to central vascular structures in the lesion, such as the hepatic artery and portal vein running from the center to the periphery, when viewed using CEUS.

Conclusion

Central vascular structures may be a characteristic finding of RNs when observed during the hepatobiliary phase of EOB-MRI and the arterial dominant phase of CEUS.

     

Randomized controlled pilot trial of mindfulness-based stress reduction compared to psychoeducational support for persistently fatigued breast and colorectal cancer survivors

Purpose

Cancer-related fatigue (CRF) is a disruptive symptom for many survivors. Despite promising evidence for efficacy of mindfulness-based stress reduction (MBSR) in reducing CRF, no trials comparing it to an active comparator for fatigued survivors have been published. The purpose of this trial was to compare MBSR to psychoeducation for CRF and associated symptoms.

Methods

Breast (n = 60) and colorectal (n = 11) cancer survivors (stage 0–III) with clinically significant CRF after completing chemotherapy and/or radiation therapy an average of 28 months prior to enrollment were randomized to MBSR or psychoeducation/support groups (PES). MBSR focused on mindfulness training; PES focused on CRF self-management. Outcomes included CRF interference (primary), CRF severity and global improvement, vitality, depression, anxiety, sleep disturbance, and pain. Outcomes were assessed at baseline (T1), post-intervention (T2), and 6-month follow-up (T3) using intent-to-treat analysis.

Results

Between-group differences in CRF interference were not significant at any time point; however, there was a trend favoring MBSR (d = ?0.46, p = 0.073) at T2. MBSR participants reported significantly greater improvement in vitality (d = 0.53, p = 0.003) and were more likely to report CRF as moderately to completely improved compared to the PES group (χ2 (1) = 4.1765, p = 0.041) at T2. MBSR participants also reported significantly greater reductions in pain at T2 (d = 0.53, p = 0.014). In addition, both MBSR and PES produced moderate-to-large and significant within-group improvements in all fatigue outcomes, depression, anxiety, and sleep at T2 and T3 compared to T1.

Conclusion

MBSR and PES appear efficacious for CRF and related symptoms. Larger trials including a usual care arm are warranted.

Trial Registration

ClinicalTrials.gov Identifier: NCT01724333.

     

Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials

Introduction

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults.

Methods

Data sources. Six electronic databases (“generalized anxiety (disorder)” and “randomized trial”) and reference lists of identified publications were searched to March 2017. Study selection. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind–body therapies). Data extraction. Cochrane Collaboration methodology was used for quality assessment and data extraction.

Results

Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: ? 3.24 (95% CI ? 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor.

Conclusion

Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

     

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.

     

How does esophagus look on barium esophagram in pediatric eosinophilic esophagitis?

Purpose

The clinical, endoscopic, and histologic findings of eosinophilic esophagitis (EoE) are well characterized; however, there have been very limited data regarding the radiologic findings of pediatric EoE. We report on the radiologic findings of pediatric EoE observed on barium esophagram and correlate them with the endoscopic findings.

Methods and materials

We identified children diagnosed with EoE in our center from 2004 to 2015. Two pediatric radiologists met after their independent evaluations of each fluoroscopic study to reach a consensus on each case. Clinical and endoscopic data were collected by retrospective chart review.

Results

Twenty-six pediatric EoE cases (age range 2–13 years; median 7.5 years) had barium esophagram done as part of the diagnostic approach for dysphagia. Thirteen children had abnormal radiologic findings of esophagus (50%): rings formation (n = 4), diffuse irregularity of mucosa (n = 8), fixed stricture formation (n = 3), and narrow-caliber esophagus (n = 10). Barium esophagram failed to show one of 10 cases of narrow-caliber esophagus and 10 of 14 cases of rings formation visualized endoscopically. The mean duration of symptoms prior to diagnosis of EoE was longer (3.7 vs. 1.7 year; p value 0.019), and the presentation with intermittent food impaction was commoner in the group with abnormal barium esophagram as compared to the group with normal barium esophagram (69% vs. 8%; p value 0.04).

Conclusion

Barium swallow study is frequently normal in pediatric EoE. With the exception of narrow-caliber esophagus, our data show poor correlation between radiologic and endoscopic findings.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Accuracy of simple approaches to assessing liver volume in radiological imaging

Objectives

The purpose of the study was to evaluate the accuracy of measured diameters and calculated volume indices for determining liver size and to derive a simple approach for estimating liver volume.

Methods

Three hundred twenty-nine volunteers (cohort A) were grouped according to liver volume: small (n = 109), medium (n = 110), and large (n = 110). True liver volume was determined by magnetic resonance imaging (MRI) using manual segmentation. Maximum diameters (maxdiam) of the liver and distances in midclavicular line (MCL) were measured. Volume indices were calculated as a simple product of the measured diameters. The calculated volume indices were calibrated to predict true liver volume. Performance of the calibrated method was evaluated in a control group (cohort B) including randomly selected volunteers (n = 110) and a patient group with histopathologically proven parenchymal liver diseases (n = 28).

Results

In cohort A, there was strong correlation between diameters and true liver volume (r _s = 0.631–0.823). Calculated volume indices had slightly better correlation (maxdiam r _s = 0.903, MCL r _s = 0.920). A calibration index was calculated from the volumes and diameters determined in cohort A. Application of this calibration on cohort B verified a very strong correlation between calibrated volume indices and true liver volume (maxdiam r _s = 0.920, MCL r _s = 0.909). In addition, the low mean difference between predicted liver volume (maxdiam = ?70.9 cm³;MCL = ?88.4 cm³) and true liver volume confirms that the calibrated method allows accurate assessment of liver volume.

Conclusions

Both simple diameters and volume indices allow estimating liver size. A simple calibration formula enables prediction of true liver volume without significant expense.

     

Usability and Acceptability of the Abatacept Pre-Filled Autoinjector for the Subcutaneous Treatment of Rheumatoid Arthritis

Introduction

The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs.

Methods

Two independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity.

Results

In the formative (pre-validation) study (n = 54), two high-priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors—formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use.

Conclusion

The abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use.

Funding

Bristol-Myers Squibb.