The symptom of fatigue impairs function in people with multiple sclerosis (MS). Choosing appropriate measures to assess fatigue is challenging. The purpose of this article is to report the findings ...of a systematic review of patient-reported fatigue measures for people with MS.
PubMed, CINAHL, and Embase databases were searched through January 2020 using terms related to fatigue and MS. Studies were included if the sample size was 30 or more or smaller samples if adequately powered, and if information about measurement characteristics (ie, test-retest reliability, content validity, responsiveness, interpretability, or generalizability) of the measure(s) could be extracted. Study quality was appraised with the 2-point COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Data about measurement characteristics, psychometrics, and clinical utility were extracted and results were synthesized.
Twenty-four articles met inclusion criteria with information about 17 patient-reported fatigue measures. No studies had critical methodologic flaws. Measurement characteristic data were not available for all measures. Clinical utility varied in time to complete and fatigue domains assessed.
Five measures had data pertaining to all properties of interest. Of these, only the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) had excellent reliability, responsiveness data, no notable ceiling/floor effects, and high clinical utility. We recommend the MFIS for comprehensive measurement and the FSS for screening of subjective fatigue in people with MS.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A443 ).
We sought to identify risk factors for central line-associated bloodstream infection (CLABSI) to describe children who might benefit from adjunctive interventions.
Case-control study of children ...admitted to the medical-surgical intensive care unit (ICU) or cardiac ICU from January 1, 2004, through December 31, 2007.
Children's Hospital Boston is a freestanding, 396-bed quaternary care pediatric hospital with a 29-bed medical-surgical ICU and a 24-bed cardiac ICU.
Case patients were patients with CLABSI who were identified by means of prospective surveillance. Control subjects were patients with a central venous catheter who were matched by ICU admission date.
Multivariate conditional logistic regression models were used to identify independent risk factors for CLABSI and to derive and to validate a prediction rule.
Two hundred three case patients were matched with 406 control subjects. Independent predictors of CLABSI included duration of ICU central access (odds ratio OR for 15 or more days, 18.41 95% confidence interval {CI}, 4.10-82.56; P < .001), central venous catheter placement in the ICU (OR for 2 or more ICU-placed catheters, 8.63 95% CI, 2.63-28.38; P = .001), nonoperative cardiovascular disease (OR, 7.44 95% CI, 2.13-25.98; P = .012), presence of gastrostomy tube (OR, 3.48 95% CI, 1.55-7.79; P = .003), receipt of parenteral nutrition (OR, 3.12 95% CI, 1.55-6.32; P = .002), and receipt of blood transfusion (OR, 2.55 95% CI, 1.21-5.36; P = .014). By use of risk factors known before central venous catheter placement, our model predicted CLABSI with a positive predictive value of 54% and a negative predictive value of 79%.
Duration of central access, receipt of parenteral nutrition, and receipt of blood transfusion were confirmed as risk factors for CLABSI among children in the ICU. Newly identified risk factors include presence of gastrostomy tube, nonoperative cardiovascular disease, and ICU placement of central venous catheter. Children with these risk factors may be candidates for adjunctive interventions for CLABSI prevention.
Various studies have described the benefits of using outcome measures (OM) in physical therapist practice; however, multiple barriers interfere with their use. Most notably, a limited understanding ...of how to select and apply the best OM has been reported to be a barrier. The purposes of this article are to: 1. describe the process used by the MSTF to evaluate the psychometric data and clinical utility of OMs for use in people with multiple sclerosis (MS), 2. describe the consensus process used to recommend OMs for this patient population, and 3. provide evidence-based recommendations to assist clinicians in selecting appropriate OMs for people with MS. Of these, 36 measured aspects of body function/ structure, 40 pertained to activity, and 17 pertained to participation. Seventeen OMs were MS specific, whereas 46 were generic or pertained to other diagnostic groups. Twenty-three of the OMs reviewed used a self-report method of administration, 38 used a performance-based method, and 2 used a combination of both methods.
Despite increased awareness of the value of treating inpatient hyperglycemia, little is known about glucose control in U.S. hospitals.
The Remote Automated Laboratory System-Plus (RALS-Plus Medical ...Automation Systems, Charlottesville, VA) was used to extract inpatient point-of-care bedside glucose (POC-BG) tests from 126 hospitals for the period January to December 2007. Patient-day-weighted mean POC-BG and hypoglycemia/hyperglycemia rates were calculated for intensive care unit (ICU) and non-ICU areas. The relationship of POC-BG levels with hospital characteristics was determined.
A total of 12,559,305 POC-BG measurements were analyzed: 2,935,167 from the ICU and 9,624,138 from the non-ICU. Patient-day-weighted mean POC-BG was 165 mg/dL for ICU and 166 mg/dL for non-ICU. Hospital hyperglycemia (>180 mg/dL) prevalence was 46.0% for ICU and 31.7% for non-ICU. Hospital hypoglycemia (<70 mg/dL) prevalence was low at 10.1% for ICU and 3.5% for non-ICU. For ICU and non-ICU there was a significant relationship between number of beds and patient-day-weighted mean POC-BG levels, with larger hospitals (> or = 400 beds) having lower patient-day weighted mean POC-BG per patient day than smaller hospitals (<200 beds, P < 0.001). Rural hospitals had higher POC-BG levels compared to urban and academic hospitals (P < 0.05), and hospitals in the West had the lowest values.
POC-BG data captured through automated data management software can support hospital efforts to monitor the status of inpatient glycemic control. From these data, hospital hyperglycemia is common, hypoglycemia prevalence is low, and POC-BG levels vary by hospital characteristics. Increased hospital participation in data collection and reporting may facilitate the creation of a national benchmarking process for the development of best practices and improved inpatient hyperglycemia management.
Peat represents a globally significant pool of sequestered carbon. However, peatland carbon stocks are highly threatened by anthropogenic climate change, including drought, which leads to a large ...release of carbon dioxide. Although the enzymatic mechanisms underlying drought-driven carbon release are well documented, the effect of drought on peatland microbial communities has been little studied. Here, we carried out a replicated and controlled drought manipulation using intact peat 'mesocosm cores' taken from bog and fen habitats, and used a combination of community fingerprinting and sequencing of marker genes to identify community changes associated with drought. Community composition varied with habitat and depth. Moreover, community differences between mesocosm cores were stronger than the effect of the drought treatment, emphasising the importance of replication in microbial marker gene studies. While the effect of drought on the overall composition of prokaryotic and eukaryotic communities was weak, a subset of the microbial community did change in relative abundance, especially in the fen habitat at 5 cm depth. 'Drought-responsive' OTUs were disproportionately drawn from the phyla Bacteroidetes and Proteobacteria. Collectively, the data provide insights into the microbial community changes occurring alongside drought-driven carbon release from peatlands, and suggest a number of novel avenues for future research.
To evaluate the diagnostic utility of publicly funded clinical exome sequencing (ES) for patients with suspected rare genetic diseases.
We prospectively enrolled 297 probands who met eligibility ...criteria and received ES across 5 sites in Ontario, Canada, and extracted data from medical records and clinician surveys. Using the Fryback and Thornbury Efficacy Framework, we assessed diagnostic accuracy by examining laboratory interpretation of results and assessed diagnostic thinking by examining the clinical interpretation of results and whether clinical-molecular diagnoses would have been achieved via alternative hypothetical molecular tests.
Laboratories reported 105 molecular diagnoses and 165 uncertain results in known and novel genes. Of these, clinicians interpreted 102 of 105 (97%) molecular diagnoses and 6 of 165 (4%) uncertain results as clinical-molecular diagnoses. The 108 clinical-molecular diagnoses were in 104 families (35% diagnostic yield). Each eligibility criteria resulted in diagnostic yields of 30% to 40%, and higher yields were achieved when >2 eligibility criteria were met (up to 45%). Hypothetical tests would have identified 61% of clinical-molecular diagnoses.
We demonstrate robustness in eligibility criteria and high clinical validity of laboratory results from ES testing. The importance of ES was highlighted by the potential 40% of patients that would have gone undiagnosed without this test.
SPI-077 and SPI-077 B103 are formulations of cisplatin encapsulated in pegylated STEALTH liposomes that accumulate in tumors. However, the extent to which active platinum (Pt) is released from the ...liposome is unknown. Thus, we evaluated the disposition of encapsulated and released Pt in plasma and tumors after administration of STEALTH liposomal and nonliposomal cisplatin.
Cisplatin (10 mg/kg), SPI-077 (10 mg/kg), and SPI-077 B103 (5 mg/kg) were administered i.v. to mice bearing B16 murine melanoma tumors. Microdialysis probes were placed into the right and left sides of each tumor, and serial samples were collected from tumor extracellular fluid (ECF) after administration of each agent. After each microdialysis procedure, tumor samples were obtained at each probe site to measure total Pt and Pt-DNA adducts. In a separate study, serial plasma samples (three mice per time point) were obtained. Unbound Pt in tumor ECF and plasma, and total Pt in tumor homogenates were measured by flameless atomic absorption spectrophotometry. Area under the tumor ECF (AUC(ECF)) concentration versus time curves of unbound Pt were calculated. Intrastrand GG (Pt-GG) and AG (Pt-AG) Pt-DNA adducts were measured via (32)P-postlabeling.
Mean+/-SD peak concentrations of total Pt in tumor homogenates after administration of cisplatin, SPI-077, and SPI-077 B-103 were 3.2+/-1.9, 11.9+/-3.0, and 3.5+/-0.3 microg/g, respectively. After cisplatin, mean+/-SD AUC(ECF) of unbound Pt was 0.72+/-0.46 microg/ml.h. There was no detectable unbound Pt in tumor ECF after SPI-077 or SPI-077 B-103 treatment. Mean+/-SD peak concentration of Pt-GG DNA adducts after administration of cisplatin, SPI-077, and SPI-077 B-103 were 13.1+/-3.3, 3.5+/-1.3, and 2.1+/-0.3 fmol Pt/microg DNA, respectively.
This study suggests that more SPI-077 and SPI-077 B103 distribute into tumors, but release less Pt into tumor ECF, and form fewer Pt-DNA adducts than does cisplatin.
Abstract
BACKGROUND
DNA and RNA-based tumor sequencing tests have the potential to guide the clinical management of children with CNS tumors. However, data describing the utility of these tests are ...limited.
METHODS
Children with high-risk or recurrent CNS tumors are included in the diverse cohort of patients enrolling in the KidsCanSeq study from six Texas sites. DNA and RNA from FFPE tumor is subjected to targeted sequencing using a 124-gene mutation panel and an 81-gene fusion panel. Tumor capture transcriptome sequencing, exome sequencing, and copy number array (as well as germline panel and exome testing) are also performed. Tumor variants are classified using AMP/ASCO/CAP consensus guidelines.
RESULTS
A total of 74 children with high-risk/recurrent CNS tumors enrolled as of 1/28/20. Targeted tumor DNA and RNA panel testing was completed for 57 patients with varied diagnoses. At least one tumor variant with strong or potential clinical significance was identified in 43 of 57 (75%) tumors, with therapeutic significance in 20 of 57 (35%) tumors. The 38 therapeutically-relevant variants most frequently affected MAPK signaling (BRAF x9, EGFR x3, FGFR2, FGFR3, KRAS, NF1, NTRK2) and the AKT/mTOR pathway (PIK3CA x3, PTEN x2, mTOR, TSC1, PIK3R1). Most had not been detected by prior targeted diagnostic testing (27/38, 71%).
CONCLUSION
Integrated DNA and RNA-based panel testing identified variants with potential to impact clinical decision-making in a majority of children with high-risk/recurrent CNS tumors. The comparative yield of panel testing vs. exome/transcriptome/array will be evaluated in the KidsCanSeq study cohort.
We surveyed US and Canadian pediatric hospitals about their use of central line-associated bloodstream infection (CLABSI) prevention strategies beyond typical insertion and maintenance bundles. We ...found wide variation in supplemental strategies across hospitals and in their penetration within hospitals. Future studies should assess specific adjunctive prevention strategies and CLABSI rates.
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