Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p

Estimating genetic diversity across the neutral genome with the use of dense marker maps

<p>Abstract</p> <p>Background</p> <p>With the advent of high throughput DNA typing, dense marker maps have become available to investigate genetic diversity on specific regions of the genome. The aim of this paper was to compare two marker based estimates of the genetic diversity in specific genomic regions lying in between markers: IBD-based genetic diversity and heterozygosity.</p> <p>Methods</p> <p>A computer simulated population was set up with individuals containing a single 1-Morgan chromosome and 1665 SNP markers and from this one, an additional population was produced with a lower marker density i.e. 166 SNP markers. For each marker interval based on adjacent markers, the genetic diversity was estimated either by IBD probabilities or heterozygosity. Estimates were compared to each other and to the true genetic diversity. The latter was calculated for a marker in the middle of each marker interval that was not used to estimate genetic diversity.</p> <p>Results</p> <p>The simulated population had an average minor allele frequency of 0.28 and an LD (r²) of 0.26, comparable to those of real livestock populations. Genetic diversities estimated by IBD probabilities and by heterozygosity were positively correlated, and correlations with the true genetic diversity were quite similar for the simulated population with a high marker density, both for specific regions (r = 0.19-0.20) and large regions (r = 0.61-0.64) over the genome. For the population with a lower marker density, the correlation with the true genetic diversity turned out to be higher for the IBD-based genetic diversity.</p> <p>Conclusions</p> <p>Genetic diversities of ungenotyped regions of the genome (i.e. between markers) estimated by IBD-based methods and heterozygosity give similar results for the simulated population with a high marker density. However, for a population with a lower marker density, the IBD-based method gives a better prediction, since variation and recombination between markers are missed with heterozygosity.</p

Validation of a method for identifying nursing home admissions using administrative claims

<p>Abstract</p> <p>Background</p> <p>Currently there is no standard algorithm to identify whether a subject is residing in a nursing home from administrative claims. Our objective was to develop and validate an algorithm that identifies nursing home admissions at the resident-month level using the MarketScan Medicare Supplemental and Coordination of Benefit (COB) database.</p> <p>Methods</p> <p>The computer algorithms for identifying nursing home admissions were created by using provider type, place of service, and procedure codes from the 2000 – 2002 MarketScan Medicare COB database. After the algorithms were reviewed and refined, they were compared with a detailed claims review by an expert reviewer. A random sample of 150 subjects from the claims was selected and used for the validity analysis of the algorithms. Contingency table analysis, comparison of mean differences, correlations, and t-test analyses were performed. Percentage agreement, sensitivity, specificity, and Kappa statistics were analyzed.</p> <p>Results</p> <p>The computer algorithm showed strong agreement with the expert review (99.9%) for identification of the first month of nursing home residence, with high sensitivity (96.7%), specificity (100%) and a Kappa statistic of 0.97. Weighted Pearson correlation coefficient between the algorithm and the expert review was 0.97 (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>A reliable algorithm indicating evidence of nursing home admission was developed and validated from administrative claims data. Our algorithm can be a useful tool to identify patient transitions from and to nursing homes, as well as to screen and monitor for factors associated with nursing home admission and nursing home discharge.</p

Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD

<p>Abstract</p> <p>Background</p> <p>A suggested role for T cells in COPD pathogenesis is based on associations between increased lung cytotoxic T lymphocyte (CD8⁺) numbers and airflow limitation. CD69 is an early T cell activation marker. Natural Killer cell group 2 D (NKG2D) receptors are co-stimulatory molecules induced on CD8⁺T cells upon activation. The activating function of NKG2 D is triggered by binding to MHC class 1 chain-related (MIC) molecules A and B, expressed on surface of stressed epithelial cells. The aim of this study was to evaluate the expression of MIC A and B in the bronchial epithelium and NKG2 D and CD69 on BAL lymphocytes in subjects with COPD, compared to smokers with normal lung function and healthy never-smokers.</p> <p>Methods</p> <p>Bronchoscopy with airway lavages and endobronchial mucosal biopsy sampling was performed in 35 patients with COPD, 21 healthy never-smokers and 16 smokers with normal lung function. Biopsies were immunohistochemically stained and BAL lymphocyte subsets were determined using flow cytometry.</p> <p>Results</p> <p>Epithelial CD3⁺lymphocytes in bronchial biopsies were increased in both smokers with normal lung function and in COPD patients, compared to never-smokers. Epithelial CD8⁺lymphocyte numbers were higher in the COPD group compared to never-smoking controls. Among gated CD3⁺cells in BAL, the percentage of CD8⁺NKG2D⁺cells was enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. The percentage of CD8⁺CD69⁺cells and cell surface expression of CD69 were enhanced in patients with COPD and smokers with normal lung function, compared to never-smokers. No changes in the expression of MIC A or MIC B in the airway epithelium could be detected between the groups, whereas significantly decreased soluble MICB was detected in bronchial wash from smokers with normal lung function, compared to never-smokers.</p> <p>Conclusions</p> <p>In COPD, we found increased numbers of cytotoxic T cells in both bronchial epithelium and airway lumen. Further, the proportions of CD69- and NKG2D-expressing cytotoxic T cells in BAL fluid were enhanced in both subjects with COPD and smokers with normal lung function and increased expression of CD69 was found on CD8⁺cells, indicating the cigarette smoke exposure-induced expansion of activated cytotoxic T cells, which potentially can respond to stressed epithelial cells.</p

Whole body composition analysis by the BodPod air-displacement plethysmography method in children with phenylketonuria shows a higher body fat percentage

BACKGROUND: Phenylketonuria (PKU) causes irreversible central nervous system damage unless a phenylalanine (PHE) restricted diet with amino acid supplementation is maintained. To prevent growth retardation, a protein/amino acid intake beyond the recommended dietary protein allowance is mandatory. However, data regarding disease and/or diet related changes in body composition are inconclusive and retarded growth and/or adiposity is still reported. The BodPod whole body air-displacement plethysmography method is a fast, safe and accurate technique to measure body composition. AIM: To gain more insight into the body composition of children with PKU. METHODS: Patients diagnosed with PKU born between 1991 and 2001 were included. Patients were identified by neonatal screening and treated in our centre. Body composition was measured using the BodPod system (Life Measurement Incorporation©). Blood PHE values determined every 1–3 months in the year preceding BodPod analysis were collected. Patients were matched for gender and age with data of healthy control subjects. Independent samples t tests, Mann–Whitney and linear regression were used for statistical analysis. RESULTS: The mean body fat percentage in patients with PKU (n = 20) was significantly higher compared to healthy controls (n = 20) (25.2% vs 18.4%; p = 0.002), especially in girls above 11 years of age (30.1% vs 21.5%; p = 0.027). Body fat percentage increased with rising body weight in patients with PKU only (R = 0.693, p = 0.001), but did not correlate with mean blood PHE level (R = 0.079, p = 0.740). CONCLUSION: Our data show a higher body fat percentage in patients with PKU, especially in girls above 11 years of age

Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent

Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women

BACKGROUND: Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used. METHODS: 1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (&gt; 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements. RESULTS: In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p &lt; 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men. CONCLUSIONS: The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later

Small area contextual effects on self-reported health: Evidence from Riverside, Calgary

<p>Abstract</p> <p>Background</p> <p>We study geographic variation within one community in the City of Calgary using a more fine-grained geographic unit than the Census tract, the Census Dissemination Area (DA). While most Riverside residents consider their neighbourhood to be a fairly cohesive community, we explore the effect of socio-economic variation between these small geographic areas on individuals' self-reported health, net of individual level determinants.</p> <p>Methods</p> <p>We merge data from the 2001 Census for Riverside, Calgary with a 2004 random telephone survey of Riverside residents. Our data are unique in that we have information on individuals from every DA wholly contained in the Riverside community. These data enable us to conduct multinomial logistic regression analyses of self-reported health using both individual-level and DA-level variables as predictors.</p> <p>Results</p> <p>We find significant variation in measures of DA socio-economic status within the Riverside community. We find that individual self-reported health is affected by variation in an index of DA-level socio-economic disadvantage, controlling for individual variation in gender, age, and socio-economic status. We investigate each aspect of the DA index of disadvantage separately, and find that average education and the percent of households that are headed by a lone parent are most important.</p> <p>Conclusions</p> <p>These findings demonstrate that, even within a cohesive community, contextual effects on health can be located at a smaller geographic level than the Census tract. Research on the effects of local area socio-economic disadvantage on health that combines administrative and survey data enables researchers to develop more comprehensive measures of social and material deprivation. Our findings suggest that both social and material deprivation affect health at the local level.</p

Measurement of D-s(+) and D-s(*+) production in B meson decays and from continuum e(+)e(-) annihilation at √s=10.6 GeV

This is the pre-print version of the Article. The official published version can be accessed from the links below. Copyright @ 2002 APSNew measurements of Ds+ and Ds*+ meson production rates from B decays and from qq̅ continuum events near the Υ(4S) resonance are presented. Using 20.8 fb-1 of data on the Υ(4S) resonance and 2.6 fb-1 off-resonance, we find the inclusive branching fractions B(B⃗Ds+X)=(10.93±0.19±0.58±2.73)% and B(B⃗Ds*+X)=(7.9±0.8±0.7±2.0)%, where the first error is statistical, the second is systematic, and the third is due to the Ds+→φπ+ branching fraction uncertainty. The production cross sections σ(e+e-→Ds+X)×B(Ds+→φπ+)=7.55±0.20±0.34pb and σ(e+e-→Ds*±X)×B(Ds+→φπ+)=5.8±0.7±0.5pb are measured at center-of-mass energies about 40 MeV below the Υ(4S) mass. The branching fractions ΣB(B⃗Ds(*)+D(*))=(5.07±0.14±0.30±1.27)% and ΣB(B⃗Ds*+D(*))=(4.1±0.2±0.4±1.0)% are determined from the Ds(*)+ momentum spectra. The mass difference m(Ds+)-m(D+)=98.4±0.1±0.3MeV/c2 is also measured.This work was supported by DOE and NSF (USA), NSERC (Canada), IHEP (China), CEA and CNRS-IN2P3 (France), BMBF (Germany), INFN (Italy), NFR (Norway), MIST (Russia), and PPARC (United Kingdom). Individuals have received support from the Swiss NSF, A. P. Sloan Foundation, Research Corporation, and Alexander von Humboldt Foundation