Abstract Objectives To systematically review the instruments used to assess postural control and fear of falling in people with chronic obstructive pulmonary disease (COPD), and to synthesize and ...evaluate their breadth of content and measurement properties. Data Sources MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL, PsycINFO, PEDro, and OTSeeker databases searched in September 2012. Study Selection Two independent reviewers performed the selection of articles, the ICF linking process and quality assessment. Only quantitative studies were included, irrespective of language or publication date. Data Extraction This systematic review comprised two phases. Phase 1 aimed to identify the commonly used instruments to assess postural control and fear of falling in the COPD literature. The breadth of content of each instrument was examined based on the International Classification of Functioning, Disability and Health (ICF). In phase 2, a measurement property search filter was adopted and used in four electronic databases to retrieve properties reported in the COPD population. The COSMIN checklist was used to assess the methodological quality of each measurement property reported. Data Synthesis Seventeen out of 401 publications were eligible in phase 1. Seventeen instruments were identified including 15 for postural control and 2 for fear of falling assessment. The Berg Balance Scale, the Short Physical Performance Battery, and the Activities-specific Balance Confidence (ABC) scale were the most frequently used instruments to assess postural control and fear of falling respectively. The ICF categories covered varied considerably among instruments. The Balance Evaluation Systems test and ABC presented the greatest breadth of content. Measurement properties reported included criterion predictive validity (4 instruments), construct validity (11 instruments) and responsiveness (1 instrument), with inconsistent findings based on ‘fair’ and ‘poor’ quality studies. Conclusions Different instruments with heterogeneous content have been used to assess postural control and fear of falling outcomes. Standardized assessment methods and best evidence on measurement properties is required in the COPD literature.
To identify measurement tools used for upper limb evaluation in people with Parkinson disease (PD), to summarize the content of each tool using the International Classification of Functioning, ...Disability and Health, and to examine the reliability, validity, clinical utility, and responsiveness of the measurement tools specific to this clinical group.
Two systematic searches of online databases included articles published from inception to November 2013.
Search 1 identified upper limb measures. Search 2 retrieved studies investigating the measurement properties of these tools in people with PD.
Independent reviewers screened articles and extracted data, classified measurement tool content on the basis of the International Classification of Functioning, Disability and Health content domains, and applied both the COnsensus-based Standards for the selection of health status Measurement INstruments checklist to evaluate the study's methodological quality and a second checklist by Terwee et al to assess the measurement tool's quality. A third reviewer adjudicated differences between reviewers. Information on clinical utility was also compiled.
The 18 identified measures included PD-specific scales, generic measures, and tools developed for other clinical populations; most measures evaluated impairments and/or activity limitations. Measurement properties of 10 of the 18 identified measures were evaluated in people with PD. No high-quality studies investigated validity or responsiveness. High-quality evidence supported the interrater reliability of some Unified Parkinson's Disease Rating Scale subtests, and lower quality studies provided limited evidence for the test-retest reliability of measures evaluating fine hand function and bradykinesia.
There are relatively few high-quality studies to support the measurement properties, particularly the validity and responsiveness, of tools currently used to evaluate upper limb disability and function in people with PD. Further research is needed to inform measurement tool selection and treatment evaluation in this clinical group.
Abstract Metastatic breast cancer (MBC) remains a terminal illness for which major treatment advances are slow to appear, and hence it is crucial that effective palliative interventions be developed ...to reduce the cancer-related symptoms of women with this condition during the remaining years of their lives. This pilot/feasibility study examined a novel, yoga-based palliative intervention, the Yoga of Awareness Program, in a sample of women with MBC. The eight-week protocol included gentle yoga postures, breathing exercises, meditation, didactic presentations, and group interchange. Outcome was assessed using daily measures of pain, fatigue, distress, invigoration, acceptance, and relaxation during two preintervention weeks and the final two weeks of the intervention. Thirteen women completed the intervention (mean age = 59; mean time since diagnosis = 7 years; two African American, 11 Caucasian). During the study, four participants had cancer recurrences, and the physical condition of several others deteriorated noticeably. Despite low statistical power, pre-to-post multilevel outcomes analyses showed significant increases in invigoration and acceptance. Lagged analyses of length of home yoga practice (controlling for individual mean practice time and outcome levels on the lagged days) showed that on the day after a day during which women practiced more, they experienced significantly lower levels of pain and fatigue, and higher levels of invigoration, acceptance, and relaxation. These findings support the need for further investigation of the effects of the Yoga of Awareness Program in women with MBC.
To determine the characteristics of motor planning surrounding initial contact during gait through examination of thigh muscle timing, amplitude, and co-contraction of the paretic and nonparetic ...limbs in people poststroke, and to investigate whether muscle timing, amplitude, and clinical performance measures of balance and mobility differ based on the level of co-contraction.
Observational study.
University-based research laboratory.
Individuals (n=27) in the subacute phase after stroke and healthy controls (n=8) (N=35).
Not applicable.
Timing (onset and offset) and normalized amplitude (percent electromyography maximum) of the biceps femoris (BF) and rectus femoris (RF) muscles were measured during terminal swing and early stance. A co-contraction index (CCI) was calculated for the BF and RF muscle activity. Individuals with CCI values equal to or below the mean of the healthy group were in the low CCI group, whereas those with values above the mean were in the high CCI group. Functional balance and mobility evaluation used the Community Balance and Mobility Scale (CB&M).
For the paretic and nonparetic limbs, measures of timing, amplitude, and co-contraction were similar for both limbs. Compared with the healthy group, the high CCI group had lower CB&M scores, longer durations, and higher levels of RF and BF muscle activity, whereas the low CCI group had electromyographic measures statistically similar to healthy controls.
The motor control of gait after subacute stroke is characterized by symmetry of timing and amplitude of muscle recruitment at the knee. High co-contraction levels surrounding the knee were associated with lower functional balance and mobility. These findings suggest a compensatory strategy of increased co-contraction in those with more impairment while maintaining symmetry of lower-limb biomechanics between limbs.
Summary Background Accurate electrocardiographic (ECG) differentiation of ventricular tachycardia (VT) from supraventricular tachycardia with aberrancy (SVT-A) on ECG is key to therapeutic ...decision-making in the emergency department (ED) setting. Objective The goal of this study was to test the accuracy and agreement of emergency medicine residents to differentiate VT from SVT-A using the Vereckei criteria. Methods Six emergency medicine residents volunteered to participate in the review of 114 ECGs from 86 patients with a diagnosis of either VT or SVT-A based on an electrophysiology study. The resident reviewers initially read 12-lead ECGs blinded to clinical information, and then one week later reviewed a subset of the same 12-lead ECGs unblinded to clinical information. Results One reviewer was excluded for failing to follow study protocol and one reviewer was excluded for reviewing less than 50 blinded ECGs. The remaining four reviewers each read 114 common ECGs blinded to clinical data and their diagnostic accuracy for VT was 74% (sensitivity 70%, specificity 80%), 75% (sensitivity 76%, specificity 73%), 61% (sensitivity 81%, specificity 25%), and 68% (sensitivity 84%, specificity 40%). The intraclass correlation coefficient (ICC) was 0.31 (95% CI 0.22–0.42). Eliminating two of the four reviewers who left a disproportionately high number of ECGs unclassified resulted in an increase in overall mean diagnostic accuracy (70–74%) and agreement (0.31–0.50) in the two remaining reviewers. Three reviewers read 45 common ECGs unblinded to clinical information and had accuracies for VT 93%, 93% and 78%. Conclusion The new single lead Vereckei criteria, when applied by emergency medicine residents achieved only fair-to-good individual accuracy and moderate agreement. The addition of clinical information resulted in substantial improvement in test characteristics. Further improvements (accuracy and simplification) of algorithms for differentiating VT from SVT-A would be helpful prior to clinical implementation.
Neuroblastoma is a common cancer in children especially those under 5-years old, however they can have varied presentations that may make diagnosis difficult. Neuroblastoma is not usually high on a ...clinician's differential for a child's gait dysfunction. We describe a case of a 6-year-old female who presented to the Emergency Department for new onset right hip pain. She had associated gait disturbance and pain with ambulation as well as a new lump on her right parietal skull. An MRI of the brain, lumbar spine, and pelvis revealed the diagnosis of a left adrenal neuroblastoma that had metastasized to the femur, the lumbar spine, and the skull. This case shows the importance of early suspicion of malignancy in a patient with seemingly disparate symptoms to ensure early intervention.
Summary Background We previously identified a functional variant in a let-7 microRNA (miRNA) complementary site in the 3′-untranslated region of the KRAS oncogene (rs61764370) which is associated ...with cancer. We aimed to investigate the association of this KRAS variant with breast cancer and tumour biology. Methods We assessed frequency distributions of the KRAS variant in 415 patients with histologically confirmed breast cancer and 457 controls from Connecticut, USA (study group 1) and association of this variant with breast-cancer subtypes in 690 Irish women with known oestrogen receptor (ER), progesterone receptor (PR), and HER2 statuses, and 360 controls (study group 2). We pooled data for study groups 1 and 2 with a cohort of 140 women with triple-negative breast cancer and 113 controls to assess the association of the KRAS variant with triple-negative breast cancer risk, and genome-wide mRNA and specific miRNA expression in patients with triple-negative breast cancer. Findings Although frequency distributions of the KRAS variant in study group 1 did not differ between all genotyped individuals, eight (33%) of 24 premenopausal women with ER/PR-negative cancer had the KRAS variant, compared with 27 (13%) of 201 premenopausal controls (p=0·015). In study group 2, the KRAS variant was significantly enriched in women with triple-negative breast cancer (19 21% of 90 cases) compared with 64 (13%) of 478 for luminal A, 13 (15%) of 87 for luminal B, and two (6%) of 35 for HER2-positive subgroups (p=0·044). Multivariate analysis in the pooled study groups showed that the KRAS variant was associated with triple-negative breast cancer in premenopausal women (odds ratio 2·307, 95% CI 1·261–4·219, p=0·0067). Gene-expression analysis of triple-negative breast-cancer tumours suggested that KRAS -variant positive tumours have significantly altered gene expression, and are enriched for the luminal progenitor and BRCA1 deficiency signatures. miRNA analysis suggested reduced levels of let-7 miRNA species in KRAS -variant tumours. Interpretation The KRAS variant might be a genetic marker for development of triple-negative breast cancer in premenopausal women, and altered gene and miRNA expression signatures should enable molecular and biological stratification of patients with this subgroup of breast cancer. Funding US National Institutes of Health.
Background Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase–mediated catabolism of ...triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. Objective The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Methods Body mass index–matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by1 H-nuclear magnetic resonance. Adenosine triphosphate–binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using 3 Hcholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Results Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low–density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Conclusions Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol.
Abstract Background The epidemiology of community-associated Clostridium difficile infection is not well known. We performed a multicenter, case-control study to further describe community-associated ...C. difficile infection and assess novel risk factors. Methods We conducted this study at 5 sites from October 2006 through November 2007. Community-associated C. difficile infection included individuals with diarrhea, a positive C. difficile toxin, and no recent (12 weeks) discharge from a health care facility. We selected controls from the same clinics attended by cases. We collected clinical and exposure data at the time of illness and cultured residual stool samples and performed ribotyping. Results Of 1041 adult C. difficile infections, 162 (15.5%) met criteria for community-associated: 66 case and 114 control patients were enrolled. Case patients were relatively young (median 64 years), female (56%), and frequently required hospitalization (38%). Antimicrobials, malignancy, exposure to high-risk persons, and remote health care exposure were independently associated with community-associated C. difficile infection. In 40% of cases, we could not confirm recent antibiotic exposure. Stomach-acid suppressants were not associated with community-associated infection, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors appeared protective. Prevalence of the hypervirulent NAP-1/027 strain was infrequent (17%). Conclusions Community-associated C. difficile infection resulted in a substantial health care burden. Antimicrobials are a significant risk factor for community-associated infection. However, other unique factors also may contribute, including person-to-person transmission, remote health care exposures, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. A role for stomach-acid suppressants in community-associated C. difficile infection is not supported.
Objective Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably ...detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). Study Design This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306). Results MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%. Conclusion High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.
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