Translating clinical training into practice in complex mental health systems: Toward opening the 'Black Box' of implementation

<p>Abstract</p> <p>Background</p> <p>Implementing clinical training in a complex health care system is challenging. This report describes two successive trainings programs in one Veterans Affairs healthcare network and the lessons we drew from their success and failures. The first training experience led us to appreciate the value of careful implementation planning while the second suggested that use of an external facilitator might be an especially effective implementation component. We also describe a third training intervention in which we expect to more rigorously test our hypothesis regarding the value of external facilitation.</p> <p>Results</p> <p>Our experiences appear to be consonant with the implementation model proposed by Fixsen. In this paper we offer a modified version of the Fixsen model with separate components related to training and implementation.</p> <p>Conclusion</p> <p>This report further reinforces what others have noted, namely that educational interventions intended to change clinical practice should employ a multilevel approach if patients are to truly benefit from new skills gained by clinicians. We utilize an implementation research model to illustrate how the aims of the second intervention were realized and sustained over the 12-month follow-up period, and to suggest directions for future implementation research. The present report attests to the validity of, and contributes to, the emerging literature on implementation research.</p

Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFβ) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

Characterization of transcription within sdr region of Staphylococcus aureus

Staphylococcus aureus is an opportunistic pathogen responsible for various infections in humans and animals. It causes localized and systemic infections, such as abscesses, impetigo, cellulitis, sepsis, endocarditis, bone infections, and meningitis. S. aureus virulence factors responsible for the initial contact with host cells (MSCRAMMs—microbial surface components recognizing adhesive matrix molecules) include three Sdr proteins. The presence of particular sdr genes is correlated with putative tissue specificity. The transcriptional organization of the sdr region remains unclear. We tested expression of the sdrC, sdrD, or sdrE genes in various in vitro conditions, as well as after contact with human blood. In this work, we present data suggesting a separation of the sdr region into three transcriptional units, based on their differential reactions to the environment. Differential reaction of the sdrD transcript to environmental conditions and blood suggests dissimilar functions of the sdr genes. SdrE has been previously proposed to play role in bone infections, whilst our results can indicate that sdrD plays a role in the interactions between the pathogen and human immune system, serum or specifically reacts to nutrients/other factors present in human blood

Systematic Review of the Relationship Between Autism Stigma and Informal Caregiver Mental Health

Families play a crucial role in determining the mental health of the autistic individual(s) they are caring for. However, the stigma associated with autism can impair caregiver health. To investigate this, empirical evidence pertaining to stigma’s impact on informal caregivers’ mental health was systematically reviewed. All twelve included studies (n = 1442 informal caregivers) consistently reported the impact of autism related stigma upon caregiver mental health to be significant, meaningful and complex. A new theoretical framework describing the relationship between stigma and caregiver mental health is constructed. Moderating variables include those both changeable through intervention (e.g. hopelessness, self-esteem, self-compassion) and not changeable (gender, culture, financial burden and time since diagnosis). Implications and recommendations for professionals, interventions and future research are proposed

Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta

Amyloid precursor protein (APP) and its extracellular domain, soluble APP alpha (sAPPα) play important physiological and neuroprotective roles. However, rare forms of familial Alzheimer’s disease are associated with mutations in APP that increase toxic amyloidogenic cleavage of APP and produce amyloid beta (Aβ) at the expense of sAPPα and other non-amyloidogenic fragments. Although mitochondrial dysfunction has become an established hallmark of neurotoxicity, the link between Aβ and mitochondrial function is unclear. In this study we investigated the effects of increased levels of neuronal APP or Aβ on mitochondrial metabolism and gene expression, in human SH-SY5Y neuroblastoma cells. Increased non-amyloidogenic processing of APP, but not Aβ, profoundly decreased respiration and enhanced glycolysis, while mitochondrial DNA (mtDNA) transcripts were decreased, without detrimental effects to cell growth. These effects cannot be ascribed to Aβ toxicity, since higher levels of endogenous Aβ in our models do not cause oxidative phosphorylation (OXPHOS) perturbations. Similarly, chemical inhibition of β-secretase decreased mitochondrial respiration, suggesting that non-amyloidogenic processing of APP may be responsible for mitochondrial changes. Our results have two important implications, the need for caution in the interpretation of mitochondrial perturbations in models where APP is overexpressed, and a potential role of sAPPα or other non-amyloid APP fragments as acute modulators of mitochondrial metabolism

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

The representation of patient experience and satisfaction in physician rating sites. A criteria-based analysis of English- and German-language sites

<p>Abstract</p> <p>Background</p> <p>Information on patient experience and satisfaction with individual physicians could play an important role for performance measures, improved health care and health literacy. Physician rating sites (PRSs) bear the potential to be a widely available source for this kind of information. However, patient experience and satisfaction are complex constructs operationalized by multiple dimensions. The way in which PRSs allow users to express and rate patient experience and satisfaction could likely influence the image of doctors in society and the self-understanding of both doctors and patients. This study examines the extent to which PRSs currently represent the constructs of patient experience and satisfaction.</p> <p>Methods</p> <p>First, a systematic review of research instruments for measuring patient experience and satisfaction was conducted. The content of these instruments was analyzed qualitatively to create a comprehensive set of dimensions for patient experience and patient satisfaction. Second, PRSs were searched for systematically in English-language and German-language search engines of Google and Yahoo. Finally, we classified every structured question asked by the different PRS using the set of dimensions of patient experience and satisfaction.</p> <p>Results</p> <p>The qualitative content analysis of the measurement instruments produced 13 dimensions of patient experience and satisfaction. We identified a total of 21 PRSs. No PRSs represented all 13 dimensions of patient satisfaction and experience with its structured questions. The 3 most trafficked English-language PRS represent between 5 and 6 dimensions and the 3 most trafficked German language PRSs between 8 and 11 dimensions The dimensions for patient experience and satisfaction most frequently represented in PRSs included diversely operationalized ones such as <it>professional competence </it>and <it>doctor-patient relationship/support</it>. However, other less complex but nevertheless important dimensions such as <it>communication skills </it>and <it>information/advice </it>were rarely represented, especially in English-language PRSs.</p> <p>Conclusions</p> <p>Concerning the potential impact of PRSs on health systems, further research is needed to show which of the current operationalizations of patient experience and satisfaction presented in our study are establishing themselves in PRSs. Independently of this factual development, the question also arises whether and to what extent health policy can and should influence the operationalization of patient experience and satisfaction in PRSs. Here, the challenge would be to produce a set of dimensions capable of consensus from among the wide range of operationalizations found by this study.</p

Update: cohort mortality study of workers highly exposed to polychlorinated biphenyls (PCBs) during the manufacture of electrical capacitors, 1940-1998

BACKGROUND: The National Institute for Occupational Safety and Health previously reported mortality for a cohort of workers considered highly exposed to polychlorinated biphenyls (PCBs) between 1939 and 1977 at two electrical capacitor manufacturing plants. The current study updated vital status, examined liver and rectal cancer mortality previously reported in excess in this cohort and evaluated mortality from non-Hodgkin's lymphoma (NHL) and cancers of the stomach, intestine, breast, prostate, skin (melanoma) and brain reported to be in excess in other cohort and case-control studies of PCB-exposed persons. METHODS: Mortality was updated through 1998 for 2572 workers. Age-, gender-, race- and calendar year-adjusted standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using U.S., state and county referent rates. SMRs using U.S. referent rates are reported. Duration of employment was used as a surrogate for exposure. RESULTS: Consistent with the previous follow-up, mortality from biliary passage, liver and gall bladder cancer was significantly elevated (11 deaths, SMR 2.11, CI 1.05 – 3.77), but mortality from rectal cancer was not (6 deaths, SMR 1.47, CI 0.54 – 3.21). Among women, mortality from intestinal cancer (24 deaths, SMR 1.89, CI 1.21 – 2.82) and from "other diseases of the nervous system and sense organs", which include Parkinson's disease and amyotrophic lateral sclerosis, (15 deaths, SMR 2.07, CI 1.16 – 3.42) were elevated. There were four ALS deaths, all women (SMR 4.35, CI 1.19–11.14). Mortality was elevated for myeloma (7 deaths, SMR 2.11, CI 0.84 – 4.34), particularly among workers employed 10 years or more (5 deaths, SMR 2.80, CI 0.91 – 6.54). No linear associations between mortality and duration of employment were observed for the cancers of interest. CONCLUSION: This update found that the earlier reported excess in this cohort for biliary, liver and gall bladder cancer persisted with longer follow-up. Excess mortality for intestinal cancer among women was elevated across categories of duration of employment; myeloma mortality was highest among those working 10 years or more. The small numbers of deaths from liver and intestinal cancers, myeloma and nervous system diseases coupled with the lack of an exposure-response relationship with duration of employment preclude drawing definitive conclusions regarding PCB exposure and these causes of death