Clinical Pathways to Disability

This paper examines the pathways by which individuals transition from healthy to disabled. Because of the high prevalence and costs associated with disability, understanding these pathways is critical to developing interventions to prevent or minimize disability. We compare two estimates of disabling conditions: those observed in medical claims and conditions indicated by the disabled individual. A small number of conditions explain about half of incident disability: arthritis, infectious disease, dementia, heart failure, diabetes, and stroke. These conditions show up in medical claims and self reports. A large number of elderly also attribute disability to old age and various symptoms. Because so many of the most disabling conditions do not have clear medical treatments, the outlook for major reductions in disability might be limited.

How Do the Better Educated Do It? Socioeconomic Status and the Ability to Cope with Underlying Impairment

There is a pronounced gradient in disability across socioeconomic groups, with better educated and higher income groups reporting substantially less disability. In this paper, we consider why that is the case, focusing on impairments in basic physical and cognitive aspects of living for the elderly. Our empirical work has two parts. First, we consider how much of this gradient in disability is a result of underlying differences in functioning versus the ability to cope with impairments. We show differences in functioning are the major part of the difference in disability, but both are important. Second, we consider how the better educated elderly cope with disability. Better educated people use substantially more assistive technology than the less educated and are more likely to use paid help. But use of these services is not the primary reason that the better educated are better able to cope. We conclude with thoughts about other potential factors that may explain differential coping.

Intensive Medical Care and Cardiovascular Disease Disability Reductions

There is little empirical evidence to explain why disability declined among the elderly over the past 20 years. In this paper, we explore the role of improved medical care for cardiovascular disease on health status improvements over time. We show that the incidence of cardiovascular disease hospitalizations remained relatively constant between 1984 and 1999 at the same time that post-event survival improved and disability declined. We find that use of appropriate therapies, including pharmaceuticals such as beta-blockers, aspirin, and ace-inhibitors, and invasive procedures, explains up to 50% and 70% of the reductions in disability and death over time, respectively. Elderly patients living in regions with high use of appropriate medical therapies had better health outcomes than patients living in low-use areas. Finally, we estimate that preventing disability after an acute event can add as much as 3.7 years of quality-adjusted life expectancy, or $316,000 of value.

FDA Actions against Misleading or Unsubstantiated Economic and Quality-of-Life Promotional Claims: An Analysis of Warning Letters and Notices of Violation

AbstractObjectivesThe objective of this study was to understand the types of economic and quality-of-life promotional claims the FDA considers false or misleading.MethodsPublicly available FDA letters (n = 569) sent to pharmaceutical companies from 1997 through 2001 for inappropriate promotional claims were reviewed. A standard data collection form was developed, including six categories for economic violations and three for QOL violations. For QOL, only letters with explicit violations for false or misleading claims using the words “quality of life” or patient “well-being” were considered. Other information collected included type of regulatory letter and media in which violations were found.ResultsTwenty-eight (4.9%) letters cited false and/or misleading economic claims. The most common economic violation was “unsupported comparative claim of effectiveness, safety, or interchangeability” (n = 14). Twenty-eight (4.9%) letters cited QOL violations, of which four contained both economic and QOL violations. The most common QOL violation was “lack of substantial evidence for QOL claims” (n = 15). None of the FDA letters used the term “patient reported outcomes.” Violations were found most frequently in brochure and Web site-based promotions.ConclusionsThe body of evidence that is emerging illustrates how the FDA is regulating promotional material containing misleading or unsubstantiated economic and QOL claims. However, knowing what constitutes an appropriate claim remains challenging because there are no formal guidelines describing what constitutes a violation, nor what level of substantiating evidence is required. More guidance may be needed to ensure appropriate use of these claims in drug promotions

The predictive power of depression screening procedures for veterans with coronary artery disease

Depression leads to a worse outcome for patients with coronary artery disease (CAD). Thus, accurately identifying depression in CAD patients is imperative. In many veterans affairs (VA) hospitals, patients are screened for depression once a year using the patient health questionnaire (PHQ-9). Although the PHQ-9 is generally considered a specific and sensitive measure of depression, there is reason to believe that these screening procedures may miss a large number of cases of depression within CAD patients and cardiology patients more generally. The goal of this study was to provide data as to the predictive power of this depression screening procedure by (a) comparing the prevalence rate of depression identified by the PHQ-9 to known prevalence rates and (b) examining whether patients identified as “depressed” also had conditions that consistently co-occur with depression (eg, post-traumatic stress disorder [PTSD], other medical issues). Participants were 813 consecutive patients who received an angiogram in the cardiac catheterization laboratory at a large VA Medical Center. Prevalence of depression was 6.9% in the overall sample and less than 6% when the sample was restricted to CAD patients with significant stenosis. Depression was significantly associated with PTSD, smoking, and alcohol problems. However, depression was not associated with other medical problems such as diabetes, renal failure, peripheral vascular disease, or anemia. In conclusion, the low prevalence rate of depression and lack of associations with comorbid medical problems may suggest that the VA’s depression screening procedures have low sensitivity for identifying depression in CAD patients. It is recommended that clinicians treating CAD regularly screen for depression and do not rely on archival depression screens

Staphylococcus aureus Biofilm and Planktonic cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes

<p>Abstract</p> <p>Background</p> <p>Many chronic diseases, such as non-healing wounds are characterized by prolonged inflammation and respond poorly to conventional treatment. Bacterial biofilms are a major impediment to wound healing. Persistent infection of the skin allows the formation of complex bacterial communities termed biofilm. Bacteria living in biofilms are phenotypically distinct from their planktonic counterparts and are orders of magnitude more resistant to antibiotics, host immune response, and environmental stress. <it>Staphylococcus aureus </it>is prevalent in cutaneous infections such as chronic wounds and is an important human pathogen.</p> <p>Results</p> <p>The impact of <it>S. aureus </it>soluble products in biofilm-conditioned medium (BCM) or in planktonic-conditioned medium (PCM) on human keratinocytes was investigated. Proteomic analysis of BCM and PCM revealed differential protein compositions with PCM containing several enzymes involved in glycolysis. Global gene expression of keratinocytes exposed to biofilm and planktonic <it>S. aureus </it>was analyzed after four hours of exposure. Gene ontology terms associated with responses to bacteria, inflammation, apoptosis, chemotaxis, and signal transduction were enriched in BCM treated keratinocytes. Several transcripts encoding cytokines were also upregulated by BCM after four hours. ELISA analysis of cytokines confirmed microarray results at four hours and revealed that after 24 hours of exposure, <it>S. aureus </it>biofilm induced sustained low level cytokine production compared to near exponential increases of cytokines in planktonic treated keratinocytes. The reduction in cytokines produced by keratinocytes exposed to biofilm was accompanied by suppressed phosphorylation of MAPKs. Chemical inhibition of MAPKs did not drastically reduce cytokine production in BCM-treated keratinocytes suggesting that the majority of cytokine production is mediated through MAPK-independent mechanisms.</p> <p>Conclusions</p> <p>Collectively the results indicate that <it>S. aureus </it>biofilms induce a distinct inflammatory response compared to their planktonic counterparts. The differential gene expression and production of inflammatory cytokines by biofilm and planktonic cultures in keratinocytes could have implications for the formation and persistence of chronic wounds. The formation of a biofilm should be considered in any study investigating host response to bacteria.</p

Intrareef variations in Li/Mg and Sr/Ca sea surface temperature proxies in the Caribbean reef‐building coral Siderastrea siderea

Caribbean sea surface temperatures (SSTs) have increased at a rate of 0.2°C per decade since 1971, a rate double that of the mean global change. Recent investigations of the coral Siderastrea siderea on the Belize Mesoamerican Barrier Reef System (MBRS) have demonstrated that warming over the last 30 years has had a detrimental impact on calcification. Instrumental temperature records in this region are sparse, making it necessary to reconstruct longer SST records indirectly through geochemical temperature proxies. Here we investigate the skeletal Sr/Ca and Li/Mg ratios of S. siderea from two distinct reef zones (forereef and backreef) of the MBRS. Our field calibrations of S. siderea show that Li/Mg and Sr/Ca ratios are well correlated with temperature, although both ratios are 3 times more sensitive to temperature change in the forereef than in the backreef. These differences suggest that a secondary parameter also influences these SST proxies, highlighting the importance for site‐ and species‐specific SST calibrations. Application of these paleothermometers to downcore samples reveals highly uncertain reconstructed temperatures in backreef coral, but well‐matched reconstructed temperatures in forereef coral, both between Sr/Ca‐SSTs and Li/Mg‐SSTs, and in comparison to the Hadley Centre Sea Ice and Sea Surface Temperature record. Reconstructions generated from a combined Sr/Ca and Li/Mg multiproxy calibration improve the precision of these SST reconstructions. This result confirms that there are circumstances in which both Li/Mg and Sr/Ca are reliable as stand‐alone and combined proxies of sea surface temperature. However, the results also highlight that high‐precision, site‐specific calibrations remain critical for reconstructing accurate SSTs from coral‐based elemental proxies