Preliminary Analysis of the Feasibility and Effectiveness of Whole Body Vibration as a Therapeutic Intervention in a Skilled Nursing Facility

Skeletal muscle sarcopenia results in loss of strength, power and functional capabilities leading to decreased independence and an increased reliance on the healthcare system. Exercise is an effective countermeasure to age related loss of muscle, but may be difficult in elderly patients with complex functional limitations. Whole body vibration (WBV) is a novel tool used to stimulate the neuromuscular system; research indicates it may improve strength, power, and balance in many populations. Purpose: The purposes of this study were to determine if WBV training is feasible in a skilled nursing facility and if standard of care (SOC) with augmented WBV training improves physical function in patients compared to SOC alone. Methods: A prospective cohort design was used to accomplish the study objectives. Twelve patients (10 females; 2 males) who were residents at a skilled nursing facility consented to the study protocol and were divided into two groups. Group 1 (CON; 73.8 ± 5.7 y; 165.0 ± 0.03 cm; 77.5 ± 11.6kg) underwent SOC therapy intervention including progressive balance, strength, and range of motion exercises. Group 2 (VIB; 74.1 ± 2.3y; 169.0 ± 0.04cm; 70.5 ± 4.3kg) underwent a similar physical therapy intervention but also completed progressive WBV treatment on a symmetrically vibrating plate (2mm; 25-35 Hz). Patients completed clinical tests of physical function before and after the 23 ± 2.3 day intervention. Physical function tests included timed up-and-go (TUG) tests from a 40cm chair and a Berg balance assessment (BBA). Additionally, manual muscle tests were completed using a hand-held dynamometer for hip flexion (HF), hip abduction (HA), knee extension (KE), knee flexion (KF), plantar flexion (PF), and dorsi-flexion (DF). Student’s t-tests were used to compare the difference scores pre- and post-intervention; alpha was set at p\u3c0.05 to determine statistical significance. Results: No adverse effects were documented in either group throughout the study. Mean physical function improved in all tested variables for both groups. However, no between group differences (CON vs. VIB) were observed in BBA (p=0.52), TUG (p=0.07), HF (p=0.80), HA (p=0.47), KE (p=0.73), KF (p=0.97), PF (p=0.59), and DF (p=0.83). Conclusions: Use of WBV as an adjunct exercise intervention in a skilled nursing facility was feasible and safe in this small sample. Although no between group differences were evident, a larger sample is needed to definitively accept or reject the hypothesis. Moreover, systematic research is needed to develop precise protocols to effectively and efficiently utilize WBV in hospitalized elders

Timed Up-And-Go Scores are Associated with Balance but not Lower-Extremity Force Production in Elderly Skilled Nursing Facility Patients

Aging is associated with numerous deleterious muscular, skeletal, and neurologic adaptations that may result in functional performance decrements. These decrements are accelerated during periods of unplanned physical inactivity (e.g. hospitalization). Reductions in gait velocity are well documented in the elderly and may result from fear of falling, poor balance, or inability to accelerate because of reduced ground reaction force capabilities. Purpose: To determine if timed up-and-go scores were related to balance or lower extremity force production in skilled nursing facility patients. Methods: Data were collected on 40 patients (77.1±1.4y; 164.2±1.7cm; 75.3±3.3 kg) in an inpatient skilled nursing facility. The 15 males and 25 female patients had a mini mental exam score of \u3e20, and provided informed consent. Each patient completed a timed up-and-go (TUG) test where they stood from a 40cm chair and walked 3 meters before circling a cone and returning to the chair. Total time from the initiation of movement until patients regained the seated position was recorded and used for analysis. The Berg Balance Test was also completed by each patient; only composite scores were used for comparison. Manual muscle tests were completed on the hip, knee, and ankle using a hand-held dynamometer that provided isometric peak force. Isometric force tests were completed for hip flexion (HF), hip abduction (HA), knee extension (KE), knee flexion (KF), plantar flexion (PF), and dorsi-flexion (DF). Pearson’s correlation coefficients were calculated between TUG and Berg composite score and isometric force production at each joint. A multiple regression model was determined using backward elimination. For each comparison, an alpha of p\u3c0.05 was used to determine statistical significance. Results: Independently, TUG times were significantly associated with Berg (r=-0.61; p \u3c0.001), but not age (r=0.24), height (r=0.22), weight (r=0.00), or force production in HF (r=-0.04), HA (r=0.06), KE (r=0.07), KF (r=0.07), DF (r=0.07), or PF (r=-0.11). The final multiple regression model derived via backward elimination explained 53% of the variance in TUG (r=-0.74) and included Berg (p\u3c0.001), HA (p=0.001) and KF (p=0.02) scores. Conclusions: These data suggest that decrements in gait performance with an agility component (TUG) are associated with balance, but poorly associated with single-joint measurements of lower extremity force production. Experimental studies are needed to determine if therapeutic interventions improving balance result in improved gait performance or if multi-joint force production tests better predict gait velocity

Reynolds-number dependence of the dimensionless dissipation rate in homogeneous magnetohydrodynamic turbulence

This paper examines the behavior of the dimensionless dissipation rate $C_{\varepsilon}$ for stationary and nonstationary magnetohydrodynamic (MHD) turbulence in presence of external forces. By combining with previous studies for freely decaying MHD turbulence, we obtain here both the most general model equation for $C_{\varepsilon}$ applicable to homogeneous MHD turbulence and a comprehensive numerical study of the Reynolds number dependence of the dimensionless total energy dissipation rate at unity magnetic Prandtl number. We carry out a series of medium to high resolution direct numerical simulations of mechanically forced stationary MHD turbulence in order to verify the predictions of the model equation for the stationary case. Furthermore, questions of nonuniversality are discussed in terms of the effect of external forces as well as the level of cross- and magnetic helicity. The measured values of the asymptote $C_{\varepsilon,\infty}$ lie between $0.193 \leqslant C_{\varepsilon,\infty} \leqslant 0.268$ for free decay, where the value depends on the initial level of cross- and magnetic helicities. In the stationary case we measure $C_{\varepsilon,\infty} = 0.223$.Comment: 18 pages, 2 figure

Lung Volume Reduction Surgery:Reinterpreted With Longitudinal Data Analyses Methodology

Background: The largest randomised controlled trial evaluating results of lung volume reduction surgery (LVRS) was conducted by the National Emphysema Treatment Trial (NETT) that published a series of reports for outcomes up to 24 months. However, patient outcomes were difficult to interpret due to limitations in and the presentation of conventional statistical analyses applied to longitudinal data. We reevaluated the NETT results using longitudinal data methodology to report longer-term outcomes to facilitate interpretation by clinicians and patients who are considering LVRS for emphysema management. Methods: Trial data were released by the United States National Institutes of Health and the National Heart, Lung, and Blood Institute and analyzed using a mixed-effects model. Data on the difference in lung function variables between patients receiving LVRS vs medical care out to 5 years were estimated and are presented. Results: The 5-year differences in patients randomised to LVRS were a small but sustained improvement in lung function indicators of forced expiratory volume in 1 second, forced vital capacity, and residual volume of +1.4% (

Pemetrexed Induced Thymidylate Synthase Inhibition in Non-Small Cell Lung Cancer Patients: A Pilot Study with 3 '-Deoxy-3 '-[F-18]fluorothymidine Positron Emission Tomography

OBJECTIVES: Pemetrexed is a thymidylate synthase (TS) inhibitor and is effective in non-small cell lung cancer (NSCLC). 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT), a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients. METHODS: Fourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET) scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST), time to progression (TTP) and overall survival (OS) were determined. RESULTS: Eleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months); median OS was 13.0 months (range 5.1-30.8 months). Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS. CONCLUSIONS: Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in ¹⁸F-FLT uptake within the tumor. No significant association with tumor response, TTP or OS was observed

Metagenes Associated with Survival in Non-Small Cell Lung Cancer

NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies

Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial

Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only moderate, with systemic relapse being the major cause of death. Pre-operative (neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage IIIA patients. We believe similar trials are now appropriate in all stages of operable lung cancer. A feasibility study was performed in 22 patients with early stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of chemotherapy [mitomycin-C 8 mg m−2, vinblastine 6 mg m−2 and cisplatin 50 mg m−2 (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible patients, 22 agreed to participate (feasibility 55%) and all complied with the full treatment schedule. All symptomatic patients achieved either complete (50%) or partial (50%) relief of tumour-related symptoms with pre-operative chemotherapy. Fifty-five per cent achieved objective tumour response, and a further 27% minor tumour shrinkage; none had progressive disease. Partial pathological response was seen in 50%. No severe (WHO grade III–IV) toxicities occurred. No significant deterioration in quality of life was detected during chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC, and this study has now been initiated as a UK-wide Medical Research Council phase III trial. © 1999 Cancer Research Campaig

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing αVβ3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and αVβ3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0–60%) expressed LH39, while αVβ3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5–90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed

Propranolol in the treatment of infantile haemangiomas:lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey

Oral propranolol is widely prescribed as first line treatment for infantile haemangiomas (IHs) and anecdotally prescribing practice differs widely between centres