Assessment of Patient Empowerment - A Systematic Review of Measures

BackgroundPatient empowerment has gained considerable importance but uncertainty remains about the best way to define and measure it. The validity of empirical findings depends on the quality of measures used. This systematic review aims to provide an overview of studies assessing psychometric properties of questionnaires purporting to capture patient empowerment, evaluate the methodological quality of these studies and assess the psychometric properties of measures identified.MethodsElectronic searches in five databases were combined with reference tracking of included articles. Peer-reviewed articles reporting psychometric testing of empowerment measures for adult patients in French, German, English, Portuguese and Spanish were included. Study characteristics, constructs operationalised and psychometric properties were extracted. The quality of study design, methods and reporting was assessed using the COSMIN checklist. The quality of psychometric properties was assessed using Terwee’s 2007 criteria.Findings30 studies on 19 measures were included. Six measures are generic, while 13 were developed for a specific condition (N=4) or specialty (N=9). Most studies tested measures in English (N=17) or Swedish (N=6). Sample sizes of included studies varied from N=35 to N=8261. A range of patient empowerment constructs was operationalised in included measures. These were classified into four domains: patient states, experiences and capacities; patient actions and behaviours; patient self-determination within the healthcare relationship and patient skills development. Quality assessment revealed several flaws in methodological study quality with COSMIN scores mainly fair or poor. The overall quality of psychometric properties of included measures was intermediate to positive. Certain psychometric properties were not tested for most measures.DiscussionFindings provide a basis from which to develop consensus on a core set of patient empowerment constructs and for further work to develop a (set of) appropriately validated measure(s) to capture this. The methodological quality of psychometric studies could be improved by adhering to published quality criteria.     

EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis

The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and induces apoptosis resistance.     

The CD4+AT2R+ T cell subpopulation improves post‐infarction remodelling and restores cardiac function

Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4⁺ AT2R⁺ cells in the rat heart and spleen post‐infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4⁺ AT2R⁺ T cells in circulating blood, post‐infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4⁺ cells. CD4⁺ AT2R⁺ T cells within blood CD4⁺ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4⁺ AT2R⁺ T cells which expressed regulatory FoxP3, secreted interleukin‐10 and other inflammatory‐related cytokines. Furthermore, intramyocardial injection of MI‐induced splenic CD4⁺ AT2R⁺ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4⁺ AT2R⁺ cells as a T cell subset improving heart function post‐MI corresponding with reduced infarction size in a rat MI‐model. Our results indicate CD4⁺ AT2R⁺ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.     

Turnover Rates of Hepatic Collagen and Circulating Collagen-Associated Proteins in Humans with Chronic Liver Disease

Accumulation and degradation of scar tissue in fibrotic liver disease occur slowly, typically over many years. Direct measurement of fibrogenesis, the rate of scar tissue deposition, may provide valuable therapeutic and prognostic information. We describe here results from a pilot study utilizing in vivo metabolic labeling to measure the turnover rate of hepatic collagen and collagen-associated proteins in plasma for the first time in human subjects. Eight subjects with chronic liver disease were labeled with daily oral doses of ²H₂O for up to 8 weeks prior to diagnostic liver biopsy and plasma collection. Tandem mass spectrometry was used to measure the abundance and fractional synthesis rate (FSR) of proteins in liver and blood. Relative protein abundance and FSR data in liver revealed marked differences among subjects. FSRs of hepatic type I and III collagen ranged from 0.2–0.6% per day (half-lives of 4 months to a year) and correlated significantly with worsening histologic fibrosis. Analysis of plasma protein turnover revealed two collagen-associated proteins, lumican and transforming growth factor beta-induced-protein (TGFBI), exhibiting FSRs that correlated significantly with FSRs of hepatic collagen. In summary, this is the first direct measurement of liver collagen turnover in vivo in humans and suggests a high rate of collagen remodeling in advanced fibrosis. In addition, the FSRs of collagen-associated proteins in plasma are measurable and may provide a novel strategy for monitoring hepatic fibrogenesis rates.     

Sleeping under the Ocean: Despite Total Isolation,Nuclear Submariners Maintain Their Sleep and Wake Patterns throughout Their Under Sea Mission

BackgroundTo assess the effects of isolation, inadequate exposure to light and specific shift work on the subjective and objective measurements of sleep and alertness of submariners.PurposeA strictly controlled randomized crossover study with the polysomnography recorded twice during the mission.MethodsSetting: Shift and night work with prolonged (70 days) social isolation from the real world (with no phone or Internet contact with families or friends during a routine mission aboard the “Téméraire” French Strategic Submarine with Ballistic Nuclear missiles (SSBN). Participants: 19 submariners working on a 24-hour shift for three days in a row schedule. Interventions: The participants attended two polysomnographic (PSG) recordings of night sleep on Day 21 (D21) and Day 51 (D51) of the 70-day patrol; urine cortisol levels were also taken after sleep, and subjective assessments of sleep, sleepiness, mood and anxiety on D21 and D51. The light and temperature on board were also recorded.ResultsPSG analyses showed that sleep did not significantly vary in length (total sleep time) or in quality between D21 and D51. The mariners reported the same subjective sleep, sleepiness, anxiety or mood (except for a slightly worse score for confusion on D51). Blood cortisol levels did not vary significantly.ConclusionsThese results show that humans living in an isolated environment for more than two months with this specific shift schedule do not suffer from any significant effects on sleep, sleepiness and confusion between D21 and D51, when they follow an organized regular shift pattern with controlled light and temperature.     

Oxidative Stress Induces Caveolin 1 Degradation and Impairs Caveolae Functions in Skeletal Muscle Cells

Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H₂O₂) at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H₂O₂ treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H₂O₂ treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H₂O₂ treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H₂O₂ decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.     

Measuring Faecal Epi-Androsterone as an Indicator of Gonadal Activity in Spotted Hyenas (Crocuta crocuta)

Enzyme immunoassays (EIA) that measure faecal testosterone metabolites (fTM) are useful tools to monitor gonadal activity. The aim of this study was to validate an “in-house” epiandrosterone EIA to monitor fTM in spotted hyenas. FTM were characterised in a male and a female hyena that each received an injection of ³H-testosterone. High-performance liquid chromatography (HPLC) analyses revealed a cluster of highly polar enzyme-hydrolysable hormone metabolite conjugates. We performed hydrolysis using β-glucuronidase to deconjugate metabolites and improve sensitivity of the assay. Because β-glucuronidase from Helix pomatia has been reported to bias testosterone measurements in some species, we compared the enzymatic activity of the commonly used β-glucuronidase extracted from H. pomatia with the same enzyme from Escherichia coli. Our results showed that β-glucuronidases from both sources produced similar results from spotted hyena faeces. We therefore hydrolysed samples with H. pomatia enzymes. HPLC analyses also demonstrated that following hydrolysis the epiandrosterone EIA measured significant amounts of immunoreactive metabolites corresponding to radiolabelled metabolites in both sexes. Additionally, HPLC and GC-MS analyses confirmed the presence of epiandrosterone in faeces of spotted hyenas. The biological relevance of the epiandrosterone EIA was validated by demonstrating (1) a significant increase in fTM levels in response to a testosterone injection within 16 h, (2) no biological responsiveness to an adrenocorticotropic hormone (ACTH) injection and (3) significant differences in fTM levels between juvenile males and adult immigrant males in a free-ranging wild population. Our results clearly demonstrate that the epiandrosterone EIA is a reliable non-invasive method to monitor gonadal activity in spotted hyenas.     

On the Relevance of Natural Stimuli for the Study of Brainstem Correlates: The Example of Consonance Perception

Some combinations of musical tones sound pleasing to Western listeners, and are termed consonant, while others sound discordant, and are termed dissonant. The perceptual phenomenon of consonance has been traced to the acoustic property of harmonicity. It has been repeatedly shown that neural correlates of consonance can be found as early as the auditory brainstem as reflected in the harmonicity of the scalp-recorded frequency-following response (FFR). “Neural Pitch Salience” (NPS) measured from FFRs—essentially a time-domain equivalent of the classic pattern recognition models of pitch—has been found to correlate with behavioral judgments of consonance for synthetic stimuli. Following the idea that the auditory system has evolved to process behaviorally relevant natural sounds, and in order to test the generalizability of this finding made with synthetic tones, we recorded FFRs for consonant and dissonant intervals composed of synthetic and natural stimuli. We found that NPS correlated with behavioral judgments of consonance and dissonance for synthetic but not for naturalistic sounds. These results suggest that while some form of harmonicity can be computed from the auditory brainstem response, the general percept of consonance and dissonance is not captured by this measure. It might either be represented in the brainstem in a different code (such as place code) or arise at higher levels of the auditory pathway. Our findings further illustrate the importance of using natural sounds, as a complementary tool to fully-controlled synthetic sounds, when probing auditory perception.