Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

Objective To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. Design Longitudinal, observational design. Setting Osteoarthritis Initiative cohort. Participants Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 Interventions Not applicable. Main Outcome Measures Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. Results Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by −.072 (95% confidence interval, −.121 to −.020). Conclusions Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower‐Extremity Symptoms

Objective To identify an evidence‐based minimum physical activity threshold to predict improved or sustained high function for adults with lower‐extremity joint symptoms. Methods Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower‐extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2‐year gait speed and patient‐reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate‐vigorous (MV) activity in bouts lasting 10 minutes or more (MV‐bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). Results Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. Conclusion These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower‐extremity joint symptoms. This evidence‐based threshold is less rigorous than federal guidelines (≥150 MV‐bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower‐extremity symptoms

A Randomized Trial of a Motivational Interviewing Intervention to Increase Lifestyle Physical Activity and Improve Self-Reported Function in Adults with Arthritis

Background Arthritis is a leading cause of chronic pain and functional limitations. Exercise is beneficial for improving strength and function and decreasing pain. We evaluated the effect of a motivational interviewing-based lifestyle physical activity intervention on self-reported physical function in adults with knee osteoarthritis (KOA) or rheumatoid arthritis (RA). Methods Participants were randomized to intervention or control. Control participants received a brief physician recommendation to increase physical activity to meet national guidelines. Intervention participants received the same brief baseline physician recommendation in addition to motivational interviewing sessions at baseline, 3, 6, and 12 months. These sessions focused on facilitating individualized lifestyle physical activity goal setting. The primary outcome was change in self-reported physical function. Secondary outcomes were self-reported pain and accelerometer-measured physical activity. Self-reported KOA outcomes were evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for KOA (WOMAC scores range from 0 to 68 for function and 0 to 20 for pain) and the Health Assessment Questionnaire (HAQ) for RA. Outcomes were measured at baseline, 3, 6, 12, and 24 months. Multiple regression accounting for repeated measures was used to evaluate the overall intervention effect on outcomes controlling for baseline values. Results Participants included 155 adults with KOA (76 intervention and 79 control) and 185 adults with RA (93 intervention and 92 control). Among KOA participants, WOMAC physical function improvement was greater in the intervention group compared to the control group [difference = 2.21 (95% CI: 0.01, 4.41)]. WOMAC pain improvement was greater in the intervention group compared to the control group [difference = 0.70 (95% CI: −0.004, 1.41)]. There were no significant changes in physical activity. Among RA participants, no significant intervention effects were found. Conclusion Participants with KOA receiving the lifestyle intervention experienced modest improvement in self-reported function and a trend toward improved pain compared to controls. There was no intervention effect for RA participants. Further refinement of this intervention is needed for more robust improvement in function, pain, and physical activity

In-Situ Nuclear Magnetic Resonance Investigation of Strain, Temperature, and Strain-Rate Variations of Deformation-Induced Vacancy Concentration in Aluminum

Critical strain to serrated flow in solid solution alloys exhibiting dynamic strain aging (DSA) or Portevin–LeChatelier effect is due to the strain-induced vacancy production. Nuclear magnetic resonance (NMR) techniques can be used to monitor in situ the dynamical behavior of point and line defects in materials during deformation, and these techniques are nondestructive and noninvasive. The new CUT-sequence pulse method allowed an accurate evaluation of the strain-enhanced vacancy diffusion and, thus, the excess vacancy concentration during deformation as a function of strain, strain rate, and temperature. Due to skin effect problems in metals at high frequencies, thin foils of Al were used and experimental results correlated with models based on vacancy production through mechanical work (vs thermal jogs), while in situ annealing of excess vacancies is noted at high temperatures. These correlations made it feasible to obtain explicit dependencies of the strain-induced vacancy concentration on test variables such as the strain, strain rate, and temperature. These studies clearly reveal the power and utility of these NMR techniques in the determination of deformation-induced vacancies in situ in a noninvasive fashion.

Identification of Compounds That Inhibit IGF-I Signaling in Hyperglycemia

Increased responsiveness of vascular cells to the growth factor IGF-I has been implicated in complications associated with diabetes. Here we describe the development of an assay and screening of a library of compounds for their ability to accelerate cleavage of the transmembrane protein integrin-associated protein (IAP) thereby disrupting the association between IAP and SHPS-1 which we have shown as critical for the enhanced response of vascular cells to IGF-I. The cell-based ELISA utilizes an antibody that specifically detects cleaved, but not intact, IAP. Of the 1040 compounds tested, 14 were considered active by virtue of their ability to stimulate an increase in antibody-binding indicative of IAP cleavage. In experiments with smooth muscle and retinal endothelial cell cultures in hyperglycemic conditions, each active compound was shown to accelerate the cleavage of IAP, and this was associated with a decrease in IAP association with SHPS-1 as determined by coimmunoprecipitation of the proteins from cell lysates. As a consequence of the acceleration in IAP cleavage, the compounds were shown to inhibit IGF-I-stimulated phosphorylation of key signaling molecules including Shc and ERK1/2, and this in turn was associated with a decrease in IGF-I-stimulated cell proliferation. Identification of these compounds that utilize this mechanism has the potential to yield novel therapeutic approaches for the prevention and treatment of vascular complications associated with diabetes

Defining Plasmodium falciparum Treatment in South West Asia: A Randomized Trial Comparing Artesunate or Primaquine Combined with Chloroquine or SP

INTRODUCTION: Antimalarial resistance has led to a global policy of artemisinin-based combination therapy. Despite growing resistance chloroquine (CQ) remained until recently the official first-line treatment for falciparum malaria in Pakistan, with sulfadoxine-pyrimethamine (SP) second-line. Co-treatment with the gametocytocidal primaquine (PQ) is recommended for transmission control in South Asia. The relative effect of artesunate (AS) or primaquine, as partner drugs, on clinical outcomes and gametocyte carriage in this setting were unknown. METHODS: A single-blinded, randomized trial among Afghan refugees in Pakistan compared six treatment arms: CQ; CQ+(single-dose)PQ; CQ+(3 d)AS; SP; SP+(single-dose)PQ, and SP+(3 d)AS. The objectives were to compare treatment failure rates and effect on gametocyte carriage, of CQ or SP monotherapy against the respective combinations (PQ or AS). Outcomes included trophozoite and gametocyte clearance (read by light microscopy), and clinical and parasitological failure. FINDINGS: A total of 308 (87%) patients completed the trial. Failure rates by day 28 were: CQ 55/68 (81%); CQ+AS 19/67 (28%), SP 4/41 (9.8%), SP+AS 1/41 (2.4%). The addition of PQ to CQ or SP did not affect failure rates (CQ+PQ 49/67 (73%) failed; SP+PQ 5/33 (16%) failed). AS was superior to PQ at clearing gametocytes; gametocytes were seen on d7 in 85% of CQ, 40% of CQ+PQ, 21% of CQ+AS, 91% of SP, 76% of SP+PQ and 23% of SP+AS treated patients. PQ was more effective at clearing older gametocyte infections whereas AS was more effective at preventing emergence of mature gametocytes, except in cases that recrudesced. CONCLUSIONS: CQ is no longer appropriate by itself or in combination. These findings influenced the replacement of CQ with SP+AS for first-line treatment of uncomplicated falciparum malaria in the WHO Eastern Mediterranean Region. The threat of SP resistance remains as SP monotherapy is still common. Three day AS was superior to single-dose PQ for reducing gametocyte carriage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00959517

Advances in Distinguishing Groundwater Influenced by Oil Sands Process-Affected Water (OSPW) from Natural Bitumen-Influenced Groundwater

The objective of this study was to advance analytical methods for detecting oil sands process-affected water (OSPW) seepage from mining containments and discriminating any such seepage from the natural bitumen background in groundwaters influenced by the Alberta McMurray formation. Improved sampling methods and quantitative analyses of two groups of monoaromatic acids were employed to analyze OSPW and bitumen-affected natural background groundwaters for source discrimination. Both groups of monoaromatic acids showed significant enrichment in OSPW, while ratios of O /O containing heteroatomic ion classes of acid extractable organics (AEOs) did not exhibit diagnostic differences. Evaluating the monoaromatic acids to track a known plume of OSPW-affected groundwater confirmed their diagnostic abilities. A secondary objective was to assess anthropogenically derived artificial sweeteners and per- and polyfluoroalkyl substances (PFAS) as potential tracers for OSPW. Despite the discovery of acesulfame and PFAS in most OSPW samples, trace levels in groundwaters influenced by general anthropogenic activities preclude them as individual robust tracers. However, their inclusion with the other metrics employed in this study served to augment the tiered, weight of evidence methodology developed. This methodology was then used to confirm earlier findings of OSPW migrations into groundwater reaching the Athabasca River system adjacent to the reclaimed pond at Tar Island Dyke

Indoor Residual Spraying in Combination with Insecticide-Treated Nets Compared to Insecticide-Treated Nets Alone for Protection against Malaria: A Cluster Randomised Trial in Tanzania.

Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) of houses provide effective malaria transmission control. There is conflicting evidence about whether it is more beneficial to provide both interventions in combination. A cluster randomised controlled trial was conducted to investigate whether the combination provides added protection compared to ITNs alone. In northwest Tanzania, 50 clusters (village areas) were randomly allocated to ITNs only or ITNs and IRS. Dwellings in the ITN+IRS arm were sprayed with two rounds of bendiocarb in 2012. Plasmodium falciparum prevalence rate (PfPR) in children 0.5-14 y old (primary outcome) and anaemia in children <5 y old (secondary outcome) were compared between study arms using three cross-sectional household surveys in 2012. Entomological inoculation rate (secondary outcome) was compared between study arms. IRS coverage was approximately 90%. ITN use ranged from 36% to 50%. In intention-to-treat analysis, mean PfPR was 13% in the ITN+IRS arm and 26% in the ITN only arm, odds ratio = 0.43 (95% CI 0.19-0.97, n = 13,146). The strongest effect was observed in the peak transmission season, 6 mo after the first IRS. Subgroup analysis showed that ITN users were additionally protected if their houses were sprayed. Mean monthly entomological inoculation rate was non-significantly lower in the ITN+IRS arm than in the ITN only arm, rate ratio = 0.17 (95% CI 0.03-1.08). This is the first randomised trial to our knowledge that reports significant added protection from combining IRS and ITNs compared to ITNs alone. The effect is likely to be attributable to IRS providing added protection to ITN users as well as compensating for inadequate ITN use. Policy makers should consider deploying IRS in combination with ITNs to control transmission if local ITN strategies on their own are insufficiently effective. Given the uncertain generalisability of these findings, it would be prudent for malaria control programmes to evaluate the cost-effectiveness of deploying the combination.\ud \u