Lumbar epidural steroids are not cost effective in sciatica

Background Lumbar Epidural Steroids Injections (ESI’s) have previously been shown to provide some degree of pain relief in sciatica. Number Needed To Treat (NNT) to achieve 50% pain relief has been estimated at 7 from the results of randomised controlled trials. Pain relief is temporary. They remain one of the most commonly provided procedures in the UK. It is unknown whether this pain relief represents good value for money. Methods 228 patients were randomised into a multi-centre Double Blind Randomised Controlled Trial. Subjects received up to 3 ESI’s or intra-spinous saline depending on response and fall off with the first injection. All other treatments were permitted. All received a review of analgesia, education and physical therapy. Quality of life was assessed using the SF36 at 6 points and compared using independent sample t-tests. Follow up was up to 1 yr. Missing data was imputed using last observation carried forward (LOCF). QALY’s (Quality of Life Years) were derived from preference based heath values (summary health utility score). SF-6D health state classification was derived from SF-36 raw score data. Standard gambles (SG) were calculated using Model 10. SG scores were calculated on trial results. LOCF was not used for this. Instead average SG were derived for a subset of patients with observations for all visits up to week 12. Incremental QALY’s were derived as the difference in the area between the SG curve for the active group and placebo group. Results SF36 domains showed a significant improvement in pain at week 3 but this was not sustained (mean 54 Active vs 61 Placebo P<0.05). Other domains did not show any significant gains compared with placebo. For derivation of SG the number in the sample in each period differed. In week 12, average SG scores for active and placebo converged. In other words, the health gain for the active group as measured by SG was achieved by the placebo group by week 12. The incremental QALY gained for a patient under the trial protocol compared with the standard care package was 0.0059350. This is equivalent to an additional 2.2 days of full health. The cost per QALY gained to the provider from a patient management strategy administering one epidural as suggested by results was £25 745.68. This result was derived assuming that the gain in QALY data calculated for patients under the trial protocol would approximate that under a patient management strategy based on the trial results (one ESI). This is above the threshold suggested by some as a cost effective treatment. Conclusions The transient benefit in pain relief afforded by ESI’s does not appear to be cost-effective. Further work is needed to develop more cost-effective conservative treatments for sciatica.

Validation of a parent-proxy quality of life questionnaire for paediatric chronic cough (PC-QOL)

Background Quality of life (QOL) measures are an important patient-relevant outcome measure for clinical studies. Currently there is no fully validated cough-specific QOL measure for paediatrics. The objective of this study was to validate a cough-specific QOL questionnaire for paediatric use. Method 43 children (28 males, 15 females; median age 29 months, IQR 20–41 months) newly referred for chronic cough participated. One parent of each child completed the 27-item Parent Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough-related measures (visual analogue score and verbal category descriptive score) on two occasions separated by 2–3 weeks. Cough counts were also objectively measured on both occasions. Results Internal consistency for both the domains and total PC-QOL at both test times was excellent (Cronbach alpha range 0.70–0.97). Evidence for repeatability and criterion validity was established, with significant correlations over time and significant relationships with the cough measures. The PC-QOL was sensitive to change across the test times and these changes were significantly related to changes in cough measures (PC-QOL with: verbal category descriptive score, rs=−0.37, p=0.016; visual analogue score, rs=−0.47, p=0.003). Significant correlations of the difference scores for the social domain of the PC-QOL and the domain and total scores of the PedsQL were also noted (rs=0.46, p=0.034). Conclusion The PC-QOL is a reliable and valid outcome measure that assesses QOL related to childhood cough at a given time point and measures changes in cough-specific QOL over time.

Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line

Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose pleiotropic effects on epithelial cells include the stimulation of motility, mitosis and tubulogenesis. These responses are mediated by the cell surface tyrosine kinase receptor c-met. Because both the cytokine and receptor are found in the gastrointestinal tract, we have studied the effects of HGF/SF on transformed gut epithelial cells which express c-met. Here we describe the response of a new transformed human jejunal epithelioid cell line (HIE-7) to HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2, Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and protein. In addition, electron microscopic analysis revealed the presence of primitive junctions and rudimentary microvilli, but features of polarization were absent. When grown on reconstituted basement membranes, HIE-7 cells formed closely associated multicellular cord-like structures adjacent to acellular spaces. However, the cells did not mature structurally, form lumen-like structures or express disaccharidase mRNA, even in the presence of recombinant HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated their rapid migration in a modified wound assay. To determine whether the motogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across reconstituted basement membranes, a Boyden chamber chemoinvasion assay was performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that crossed the basement membrane barrier, while only stimulating a small increase in chemotaxis across a collagen IV matrix, suggesting that the cytokine activates matrix penetration by these cells. rHGF also stimulated the invasion of basement membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948). In contrast, two moderately well differentiated colon cancer cell lines (Caco-2 and HT-29) did not manifest an invasive response when exposed to rHGF. These results suggest that HGF/SF may play a significant role in the invasive behavior of anaplastic and poorly differentiated gut epithelial tumors.

Demonstration of nonlinear absorption in Au semi-continuous film by electrical measurement

We have demonstrated the nonlinear absorption at 532 nm wavelength in an Au semi-continuous film (SF) resulting from smearing of the Fermi distribution and diffusion of conduction electrons into the substrate. The Au SF was irradiated by a pulsed laser with 8 ns pulse width at 532 nm in near resonance with the interband transition of the Au. We determined the temperature increase in the SF for different intensities by electrical measurement. We calculated the temperature increase by using a 1D heat transport equation; comparing the results of the calculation with measured values for the temperature increase, revealed the nonlinear absorption in the Au SF. We employed this deviation from linear behaviour to determine the nonlinear absorption coefficient.

Myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones include double-positive CD8+CD4+ T cells : evidence from myeloma-bearing mouse model

The graft-versus-myeloma (GVM) effect represents a powerful form of immune attack exerted by alloreactive T cells against multiple myeloma cells, which leads to clinical responses in multiple myeloma transplant recipients. Whether myeloma cells are themselves able to induce alloreactive T cells capable of the GVM effect is not defined. Using adoptive transfer of T naive cells into myeloma-bearing mice (established by transplantation of human RPMI8226-TGL myeloma cells into CD122(+) cell-depleted NOD/SCID hosts), we found that myeloma cells induced alloreactive T cells that suppressed myeloma growth and prolonged survival of T cell recipients. Myeloma-induced alloreactive T cells arising in the myeloma-infiltrated bones exerted cytotoxic activity against resident myeloma cells, but limited activity against control myeloma cells obtained from myeloma-bearing mice that did not receive T naive cells. These myeloma-induced alloreactive T cells were derived through multiple CD8(+) T cell divisions and enriched in double-positive (DP) T cells coexpressing the CD8alphaalpha and CD4 coreceptors. MHC class I expression on myeloma cells and contact with T cells were required for CD8(+) T cell divisions and DP-T cell development. DP-T cells present in myeloma-infiltrated bones contained a higher proportion of cells expressing cytotoxic mediators IFN-gamma and/or perforin compared with single-positive CD8(+) T cells, acquired the capacity to degranulate as measured by CD107 expression, and contributed to an elevated perforin level seen in the myeloma-infiltrated bones. These observations suggest that myeloma-induced alloreactive T cells arising in myeloma-infiltrated bones are enriched with DP-T cells equipped with cytotoxic effector functions that are likely to be involved in the GVM effect.

Predictors of mental health in midlife and older women : results from the Australian Healthy Aging of Women Study

Purpose: To examine the extent to which socio-demographic characteristics, modifiable lifestyle factors and health status influence the mental health of midlife and older Australian women from the Australian Healthy Aging of Women (HOW) study. Methods: Data on health status, chronic disease and modifiable lifestyle factors were collected from a random sample of 340 women aged 40-65 years, residing in Queensland, Australia in 2011. Structural equation modelling (SEM) was used to measure the effect of a range of socio-demographic characteristics (marital status, age, income), modifiable lifestyle factors (caffeine intake, alcohol consumption, exercise, physical activity, sleep), and health markers (self-reported physical health, history of chronic illness) on the latent construct, mental health. Mental health was evaluated using the Medical Outcomes Study Short Form 12 (SF-12®) and the Center for Epidemiologic Studies Depression Scale (CES-D). Results: The model was a good fit for the data (χ2 = 40.166, df =312, p 0.125, CFI = 0.976, TLI = 0.950, RMSEA = 0.030, 90% CI = 0.000-0.053); the model suggested mental health was negatively influenced by sleep disturbance (β = -0.628), sedentary lifestyle (β = -0.137), having been diagnosed with one or more chronic illnesses (β = -0.203), and poor self-reported physical health (β = - 0.161). While mental health was associated with sleep, it was not correlated with many other lifestyle factors (BMI (β = -0.050), alcohol consumption (β = 0.079), or cigarette smoking (β = 0.008)) or background socio-demographic characteristics (age (β = 0.078), or income (β = -0.039)). Conclusion: While research suggests that it is important to engage in a range health promoting behaviours to preserve good health, we found that only sleep disturbance, physical health, chronic illness and level of physical activity predicted current mental health. However, while socio-demographic characteristics and modifiable lifestyle factors seemed to have little direct impact on mental health, they probably had an indirect effect.

Physical activity, walking and quality of life in women with depressive symptoms

Background Physical activity (PA) has a positive association with health-related quality of life (HRQL) in the general population. The association between PA and HRQL in those with poor mental health is less clear. Purpose To examine the concurrent and prospective dose-response relationships between total physical activity (TPA) and walking only with HRQL in women aged 50-55 with depressive symptoms in 2001. Methods Participants were 1904 women born in 1946-1951 who completed mailed surveys for the Australian Longitudinal Study on Women's Health in 2001, 2004, 2007 and 2010 and who, in 2001, reported depressive symptoms. At each time point, they reported their weekly minutes of walking, moderate PA, and vigorous PA. A summary TPA score was created that accounted for differences in energy expenditure among the three PA types. Mixed models were used to examine associations between TPA and HRQL (SF-36 component and subscale scores) and between walking and HRQL, for women who reported walking as their only PA. Analyses were conducted in 2013-2014. Results Concurrently, higher levels of TPA and walking were associated with better HRQL (p<0.05). The strongest associations were found for physical functioning, vitality, and social functioning subscales. In prospective models, associations were attenuated, yet compared with women doing no TPA or walking, women doing “sufficient” TPA or walking had significantly better HRQL over time for most SF-36 scales. Conclusions This study extends previous work by demonstrating trends between both TPA and walking and HRQL in women reporting depressive symptoms.

Self-efficacy moderation and mediation roles on BPSD and social support influences on subjective caregiver burden in Chinese spouse caregivers of dementia patients

Background: This study aims to explore moderation and mediation roles of caregiver self-efficacy between subjective caregiver burden and (a) behavioral and psychological symptoms (BPSD) of dementia; and (b) social support. Methods: A cross-sectional study with 137 spouse caregivers of dementia patients was conducted in Shanghai. We collected demographic information for the caregiver–patient dyads, as well as information associated with dementia-related impairments, caregiver social support, caregiver self-efficacy, and SF-36. Results: Multiple regression analysis showed that caregiver self-efficacy was a moderator both between BPSD and subjective caregiver burden, and social support and subjective caregiver burden. Results also showed a partial mediation effect of caregiver self-efficacy on the impact of BPSD on subjective caregiver burden, and a mediation effect of social support on subjective caregiver burden. Caregiver self-efficacy and subjective burden significantly influenced BPSD and social support. Conclusion: Caregiver self-efficacy played an important role in the paths by which the two factors influenced subjective burden. Enhancing caregiver self-efficacy for symptom management (particularly BPSD) can be an essential strategy for determining interventions to support dementia caregivers in China, and possibly in other countries.

A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

An acute cough-specific quality of life questionnaire for children: Development and validation

Background Patient-relevant outcome measures are essential for high-quality clinical research, and quality-of-life (QoL) tools are the current standard. Currently, there is no validated children's acute cough-specific QoL questionnaire. Objective The objective of this study was to develop and validate the Parent-proxy Children's Acute Cough-specific QoL Questionnaire (PAC-QoL). Methods Using focus groups, a 48-item PAC-QoL questionnaire was developed and later reduced to 16 items by using the clinical impact method. Parents of children with a current acute cough (<2 weeks) at enrollment completed 2 validated cough score measures, the preliminary 48-item PAC-QoL, and 3 other questionnaires (the State Trait Anxiety Inventory [STAI], the Short-Form 8-item 24-hour recall Health Survey [SF-8], and the Depression, Anxiety, and Stress 21-item Scale [DASS21]). All measures were repeated on days 3 and 14. Results The median age of the 155 children enrolled was 2.3 years (interquartile range, 1.3-4.6). Median cough duration at enrollment was 3 days (interquartile range, 2-5). The reduced 16-item scale had high internal consistency (Cronbach α = 0.95). Evidence for repeatability and criterion validity was shown by significant correlations between the domains and total PAC-QoL scores and the SF-8 (r = −0.36 and −0.51), STAI (r = −0.27 and −0.39), and DASS21 (r = −0.32 and −0.41) scales on days 0 and 3, respectively. The final PAC-QoL questionnaire was sensitive to change over time, with changes significantly relating to changes in cough score measures (P < .001). Conclusion The 16-item PAC-QoL is a reliable and valid outcome measure that assesses QoL related to childhood acute cough at a given time point and reflects changes in acute cough-specific QoL over time.

Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: A randomized controlled pilot trial of The Pink Women’s Wellness Program

OBJECTIVE Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms. The aims of this pilot study were to (1) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and (2) examine the impact of the program on health-related quality of life (HRQoL) and adherence to lifestyle recommendations. METHODS Overall, 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were randomized into an intervention group (n = 26) or a control group (n = 29). Women in the intervention group received a lifestyle intervention (The Pink Women’s Wellness Program) that included clinical consultations and a tailored health education program. Measurements of menopausal symptoms (Greene Climacteric Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy—Breast), and modifiable lifestyle factors (food intake, physical activity, smoking and alcohol use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS Women in the intervention group reported clinically significant reductions in many menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d = 0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18, and d = 0.05, respectively). Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy—Breast subscale scores, physical well-being and functional well-being, and Functional Assessment of Cancer Therapy—General total scores (intervention group: d = 0.54, d = 0.50, and d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05, respectively). CONCLUSIONS The Pink Women’s Wellness Program is effective in decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study, further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms.

The mechanical and inflammatory low back pain (MIL) index: development and validation

Abstract Background The purpose of this study was the development of a valid and reliable “Mechanical and Inflammatory Low Back Pain Index” (MIL) for assessment of non-specific low back pain (NSLBP). This 7-item tool assists practitioners in determining whether symptoms are predominantly mechanical or inflammatory. Methods Participants (n = 170, 96 females, age = 38 ± 14 years-old) with NSLP were referred to two Spanish physiotherapy clinics and completed the MIL and the following measures: the Roland Morris Questionnaire (RMQ), SF-12 and “Backache Index” (BAI) physical assessment test. For test-retest reliability, 37 consecutive patients were assessed at baseline and three days later during a non-treatment period. Face and content validity, practical characteristics, factor analysis, internal consistency, discriminant validity and convergent validity were assessed from the full sample. Results A total of 27 potential items that had been identified for inclusion were subsequently reduced to 11 by an expert panel. Four items were then removed due to cross-loading under confirmatory factor analysis where a two-factor model yielded a good fit to the data (χ2 = 14.80, df = 13, p = 0.37, CFI = 0.98, and RMSEA = 0.029). The internal consistency was moderate (α = 0.68 for MLBP; 0.72 for ILBP), test-retest reliability high (ICC = 0.91; 95%CI = 0.88-0.93) and discriminant validity good for either MLBP (AUC = 0.74) and ILBP (AUC = 0.92). Convergent validity was demonstrated through similar but weak correlations between the ILBP and both the RMQ and BAI (r = 0.34, p < 0.001) and the MLBP and BAI (r = 0.38, p < 0.001). Conclusions The MIL is a valid and reliable clinical tool for patients with NSLBP that discriminates between mechanical and inflammatory LBP. Keywords: Low back pain; Psychometrics properties; Pain measurement; Screening tool; Inflammatory; Mechanical

Energy use assessment of educational buildings: Toward a campus-wide sustainable energy policy

The purpose of this article is to assess the viability of blanket sustainability policies, such as Building Rating Systems in achieving energy efficiency in university campus buildings. We analyzed the energy consumption trends of 10 LEED-certified buildings and 14 non-LEED certified buildings at a major university in the US. Energy Use Intensity (EUI) of the LEED buildings was significantly higher (EUILEED= 331.20 kBtu/sf/yr) than non-LEED buildings (EUInon-LEED=222.70 kBtu/sf/yr); however, the median EUI values were comparable (EUILEED= 172.64 and EUInon-LEED= 178.16). Because the distributions of EUI values were non-symmetrical in this dataset, both measures can be used for energy comparisons—this was also evident when EUI computations exclude outliers, EUILEED=171.82 and EUInon-LEED=195.41. Additional analyses were conducted to further explore the impact of LEED certification on university campus buildings energy performance. No statistically significant differences were observed between certified and non-certified buildings through a range of robust comparison criteria. These findings were then leveraged to devise strategies to achieve sustainable energy policies for university campus buildings and to identify potential issues with portfolio level building energy performance comparisons.

The validity of personal disturbance scale (DSSI/sAD) in people with diabetes mellitus, using longitudinal data

Despite being used since 1976, Delusions-Symptoms-States-Inventory/states of Anxiety and Depression (DSSI/sAD) has not yet been validated for use among people with diabetes. The aim of this study was to examine the validity of the personal disturbance scale (DSSI/sAD) among women with diabetes using Mater-University of Queensland Study of Pregnancy (MUSP) cohort data. The DSSI subscales were compared against DSM-IV disorders, the Mental Component Score of the Short Form 36 (SF-36 MCS), and Center for Epidemiologic Studies Depression Scale (CES-D). Factor analyses, odds ratios, receiver operating characteristic (ROC) analyses and diagnostic efficiency tests were used to report findings. Exploratory factor analysis and fit indices confirmed the hypothesized two-factor model of DSSI/sAD. We found significant variations in the DSSI/sAD domain scores that could be explained by CES-D (DSSI-Anxiety: 55%, DSSI-Depression: 46%) and SF-36 MCS (DSSI-Anxiety: 66%, DSSI-Depression: 56%). The DSSI subscales predicted DSM-IV diagnosed depression and anxiety disorders. The ROC analyses show that although the DSSI symptoms and DSM-IV disorders were measured concurrently the estimates of concordance remained only moderate. The findings demonstrate that the DSSI/sAD items have similar relationships to one another in both the diabetes and non-diabetes data sets which therefore suggest that they have similar interpretations.

Association between single-nucleotide polymorphisms in growth factor genes and quality of life in men with prostate cancer and the general population

Purpose Improved survival for men with prostate cancer has led to increased attention to factors influencing quality of life (QOL). As protein levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1) have been reported to be associated with QOL in people with cancer, we sought to identify whether single-nucleotide polymorphisms (SNPs) of these genes were associated with QOL in men with prostate cancer. Methods Multiple linear regression of two data sets (including approximately 750 men newly diagnosed with prostate cancer and 550 men from the general population) was used to investigate SNPs of VEGF and IGF-1 (10 SNPs in total) for associations with QOL (measured by the SF-36v2 health survey). Results Men with prostate cancer who carried the minor ‘T’ allele for IGF-1 SNP rs35767 had higher mean Role-Physical scale scores (≥0.3 SD) compared to non-carriers (p < 0.05). While this association was not identified in men from the general population, one IGF-1 SNP rs7965399 was associated with higher mean Bodily Pain scale scores in men from the general population that was not found in men with prostate cancer. Men from the general population who carried the rare ‘C’ allele had higher mean Bodily Pain scale scores (≥0.3 SD) than non-carriers (p < 0.05). Conclusions Through identifying SNPs that are associated with QOL in men with prostate cancer and men from the general population, this study adds to the mapping of complex interrelationships that influence QOL and suggests a role for IGF-I in physical QOL outcomes. Future research may identify biomarkers associated with increased risk of poor QOL that could assist in the provision of pre-emptive support for those identified at risk.