Correlation of pain relief with physical function in hand osteoarthritis: randomized controlled trial post hoc analysis

Abstract Introduction Nonsteroidal anti-inflammatory drugs are recommended for the relief of pain associated with hand osteoarthritis (OA) but do not alter the underlying structural changes that contribute to impaired physical function. The current analysis examined the relationship of pain relief with measures of function and global rating of disease in patients with hand OA. Methods This was a combined analysis of 2 prospective, randomized, double-blind, 8-week, multicenter, parallel-group studies comparing diclofenac sodium 1% gel with placebo gel (vehicle) in patients with radiographically confirmed mild to moderate hand OA. Patients (n = 783) aged ≥ 40 years applied diclofenac sodium 1% gel (2 g) or vehicle to each hand 4 times daily for 8 weeks. Outcome measures included pain intensity assessed on a 100-mm Visual Analog Scale (VAS); the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) subscales for pain, stiffness, and physical function (100-mm VAS); and a global rating of disease (100-mm VAS). Change in VAS pain intensity from baseline to week 8 was categorized (<0%, 0%-<15%, 15%-<30%, 30%-<50%, 50%-<70%, and ≥ 70%) without regard to treatment and compared in each category with the mean change from baseline in each AUSCAN subindex and the global rating of disease. Pearson correlations between changes in outcome measures from baseline to week 8 were calculated. Results Changes in VAS pain intensity were accompanied by similar changes in AUSCAN scores and global rating of disease. Pearson correlations confirmed significant associations (P < 0.001) between change in VAS pain intensity and changes in AUSCAN pain (correlation coefficient [r] = 0.81), AUSCAN function (r = 0.75), AUSCAN stiffness (r = 0.66), and global rating of disease (r = 0.76). Conclusions Pain relief correlated with improvements in physical function, stiffness, and global rating of disease in patients with hand OA, irrespective of treatment. This suggests that pain or anticipation of pain inhibits physical function and influences patient perception of disease severity in hand OA. These results also suggest that any intervention to relieve the pain of hand OA may improve function and patient perception of disease severity, despite the absence of a disease-modifying mechanism of action. Trial registration Clinicaltrials.gov NCT00171652, NCT00171665

To Act and Learn: A Bakhtinian Exploration of Action Learning

This paper considers the work of the Russian social philosopher and cultural theorist, Mikhail Mikhailovich Bakhtin as a source of understanding for those involved in action learning. Drawing upon data gathered over two years during the evaluation of 20 action learning sets in the north of England, we will seek to work with the ideas of Bakhtin to consider their value for those involved in action learning. We consider key Bakhtin features such as Making Meaning, Participative Thinking, Theoreticism and Presence, Others and Outsideness, Voices and Carnival to highlight how Bakhtin's can enhance our understanding of the nature of action and learning

Childhood tetanus in Australia: ethical issues for a should-be-forgotten preventable disease

Refusal of a parent to have a child vaccinated against tetanus raised ethical issues for the treating clinicians. The clinicians felt their duty to the child was compromised, but recognised that our society leaves the authority for such decisions with the parents. As there was no reason, other than different beliefs about vaccination, to doubt the parent\u27s care for the child, the clinicians limited their response to providing strong recommendations in favour of vaccination. Other issues raised by this case include community protection, and the costs to the community of treating a vaccine-preventable disease

Multisector Dynamics: Advancing the Science of Complex Adaptive Human-Earth Systems

The field of MultiSector Dynamics (MSD) explores the dynamics and co-evolutionary pathways of human and Earth systems with a focus on critical goods, services, and amenities delivered to people through interdependent sectors. This commentary lays out core definitions and concepts, identifies MSD science questions in the context of the current state of knowledge, and describes ongoing activities to expand capacities for open science, leverage revolutions in data and computing, and grow and diversify the MSD workforce. Central to our vision is the ambition of advancing the next generation of complex adaptive human-Earth systems science to better address interconnected risks, increase resilience, and improve sustainability. This will require convergent research and the integration of ideas and methods from multiple disciplines. Understanding the tradeoffs, synergies, and complexities that exist in coupled human-Earth systems is particularly important in the context of energy transitions and increased future shocks

Air Pollution and ST-Segment Depression in Elderly Subjects

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic

Internet-Based Photoaging Within Australian Pharmacies to Promote Smoking Cessation: Randomized Controlled Trial

Background: Tobacco smoking leads to death or disability and a drain on national resources. The literature suggests that cigarette smoking continues to be a major modifiable risk factor for a variety of diseases and that smokers aged 18-30 years are relatively resistant to antismoking messages due to their widely held belief that they will not be lifelong smokers. Objective: To conduct a randomized controlled trial (RCT) of a computer-generated photoaging intervention to promote smoking cessation among young adult smokers within a community pharmacy setting. Methods: A trial was designed with 80% power based on the effect size observed in a published pilot study; 160 subjects were recruited (80 allocated to the control group and 80 to the intervention group) from 8 metropolitan community pharmacies located around Perth city center in Western Australia. All participants received standardized smoking cessation advice. The intervention group participants were also digitally photoaged by using the Internet-based APRIL Face Aging software so they could preview images of themselves as a lifelong smoker and as a nonsmoker. Due to the nature of the intervention, the participants and researcher could not be blinded to the study. The main outcome measure was quit attempts at 6-month follow-up, both self-reported and biochemically validated through testing for carbon monoxide (CO), and nicotine dependence assessed via the Fagerström scale.Results: At 6-month follow-up, 5 of 80 control group participants (6.3%) suggested they had quit smoking, but only 1 of 80 control group participants (1.3%) consented to, and was confirmed by, CO validation. In the intervention group, 22 of 80 participants (27.5%) reported quitting, with 11 of 80 participants (13.8%) confirmed by CO testing. This difference in biochemically confirmed quit attempts was statistically significant (χ21=9.0, P=.003). A repeated measures analysis suggested the average intervention group smoking dependence score had also significantly dropped compared to control participants (P<.001). These differences remained statistically significant after adjustment for small differences in gender distribution and nicotine dependence between the groups. The mean cost of implementing the intervention was estimated at AU $5.79 per participant. The incremental cost-effectiveness ratio was AU$46 per additional quitter. The mean cost that participants indicated they were willing to pay for the digital aging service was AU $20.25 (SD 15.32). Conclusions: Demonstrating the detrimental effects on facial physical appearance by using a computer-generated simulation may be both effective and cost-effective at persuading young adult smokers to quit

Alzheimer\u27s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially During Resting and Task States

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults

Evidence regarding clinical use of microvolt T-wave alternans

Background: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. Objective: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. Methods: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (≤15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). Results: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. Conclusion: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD

Differential expression of transforming growth factor-β isoforms and receptors in experimental membranous nephropathy

Transforming growth factor-β1 stimulates matrix production by glomerular mesangial and epithelial cells. In membranous nephropathy (MN) overproduction of matrix by glomerular epithelial cells (GEC) is believed to be responsible for glomerular basement membrane thickening and spikes. We studied experimental MN in rats (passive Heymann nephritis, PHN) at 5, 10 and 30 days. PHN rats exhibited a marked increase in GEC immunostaining for TGF-β2 at all time points. TGF-β3 staining was increased at day 10 only, and TGF-β1 was unchanged. Glomerular mRNA for TGF-β2 and -β3 was increased by day 5 when urine protein increased, whereas TGF-β1 was not. TGF-β2 bioactivity was increased at day 5. There was also a marked increase in GEC immunostaining for TGF-β receptor type I (TβIR) and TGF-β receptor type II (TβIIR) at all time points in PHN. mRNA levels for both receptors increased at day 5. Increases in protein expression and mRNA levels for the TGF-β2 and -β3 isoforms, and TβIR and TβRII were prevented by complement depletion. We conclude that complement-mediated injury to the GEC in vivo is associated with the up-regulation of TGF-β2 and -β3 isoforms, an increase in TGF-β2 bioactivity, and an increase in TβRI and TβRII expression. This contrasts with changes in TGF-β1 reported in mesangial disease, suggesting that TGF-β2 and -β3 may be important in diseases of the GEC. The differential expression of TGF-β isoforms and receptors may be important determinants of the GEC response to injury

Motor Preparatory Activity in Posterior Parietal Cortex is Modulated by Subjective Absolute Value

For optimal response selection, the consequences associated with behavioral success or failure must be appraised. To determine how monetary consequences influence the neural representations of motor preparation, human brain activity was scanned with fMRI while subjects performed a complex spatial visuomotor task. At the beginning of each trial, reward context cues indicated the potential gain and loss imposed for correct or incorrect trial completion. FMRI-activity in canonical reward structures reflected the expected value related to the context. In contrast, motor preparatory activity in posterior parietal and premotor cortex peaked in high “absolute value” (high gain or loss) conditions: being highest for large gains in subjects who believed they performed well while being highest for large losses in those who believed they performed poorly. These results suggest that the neural activity preceding goal-directed actions incorporates the absolute value of that action, predicated upon subjective, rather than objective, estimates of one's performance