Preparing pharmacists to deliver a targeted service in hypertension management: Evaluation of an interprofessional training program

© 2015 Bajorek et al. Background: Non-adherence to medicines by patients and suboptimal prescribing by clinicians underpin poor blood pressure (BP) control in hypertension. In this study, a training program was designed to enable community pharmacists to deliver a service in hypertension management targeting therapeutic adjustments and medication adherence. A comprehensive evaluation of the training program was undertaken. Methods: Tailored training comprising a self-directed pre-work manual, practical workshop (using real patients), and practice scenarios, was developed and delivered by an inter-professional team (pharmacists, GPs). Supported by practical and written assessment, the training focused on the principles of BP management, BP measurement skills, and adherence strategies. Pharmacists' experience of the training (expectations, content, format, relevance) was evaluated quantitatively and qualitatively. Immediate feedback was obtained via a questionnaire comprising Likert scales (1∈=∈"very well" to 7∈=∈"poor") and open-ended questions. Further in-depth qualitative evaluation was undertaken via semi-structured interviews several months post-training (and post service implementation). Results: Seventeen pharmacists were recruited, trained and assessed as competent. All were highly satisfied with the training; other than the 'amount of information provided' (median score∈=∈5, "just right"), all aspects of training attained the most positive score of '1'. Pharmacists most valued the integrated team-based approach, GP involvement, and inclusion of real patients, as well as the pre-reading manual, BP measurement workshop, and case studies (simulation). Post-implementation the interviews highlighted that comprehensive training increased pharmacists' confidence in providing the service, however, training of other pharmacy staff and patient recruitment strategies were highlighted as a need in future. Conclusions: Structured, multi-modal training involving simulated and inter-professional learning is effective in preparing selected community pharmacists for the implementation of new services in the context of hypertension management. This training could be further enhanced to prepare pharmacists for the challenges encountered in implementing and evaluating services in practice

Psychiatry out-of-hours: a focus group study of GPs' experiences in Norwegian casualty clinics

Background: For Norwegian general practitioners (GPs), acute treatment of mental illness and substance abuse are among the most commonly experienced emergency situations in out-of-hours primary healthcare. The largest share of acute referrals to emergency psychiatric wards occurs out-of-hours, and out-of-hours services are responsible for a disproportionately high share of compulsory referrals. Concerns exist regarding the quality of mental healthcare provided in the out-of-hours setting. The aim of this study was to explore which challenges GPs experience when providing emergency care out-of-hours to patients presenting problems related to mental illness or substance abuse. Methods: We conducted a qualitative study based on two individual interviews and six focus groups with purposively sampled GPs (totally 45 participants). The interviews were analysed successively in an editing style, using a thematic approach based on methodological descriptions by Charmaz and Malterud. Results: Safety and uncertainty were the dominating themes in the discussions. The threat to personal safety due to unpredictable patient behaviour was a central concern, and present security precautions in the out-of-hours services were questioned. The GPs expressed high levels of uncertainty in their work with patients presenting problems related to mental illness or substance abuse. The complexity of the problems presented, shortage of time, limited access to reliable information and limited range of interventions available during out-of-hours contributed to this uncertainty. Perceived access to second opinion seemed to have a major impact on subjectively experienced work stress. Conclusions: The GPs experienced out-of-hours psychiatry as a field with high levels of uncertainty and limited support to help them meet the experienced challenges. This might influence the quality of care provided. If the current organisation of emergency mental healthcare is to be kept, we need to provide GPs with a better support framework out-of-hours

Violence in health care: the contribution of the Australian Patient Safety Foundation to incident monitoring and analysis

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Because of growing concern about violence in health care in Australia, we reviewed the relevant data on incidents involving violence collected using the Australian Incident Monitoring System (AIMS). Among 42 338 incidents reported from 1 July 2000 to 30 June 2002, 3621 (9% of all incidents) involved patients and physical violence or violent verbal exchange; staff injury was reported in 5% of cases. The proportion was higher in emergency departments (16%, with frequent involvement of mental health problems or alcohol or drug intoxication) and mental health units (28%). Contributing factors include changes in our society and in mental health service provision. With the closure of public psychiatric hospitals in the past decade, more patients with mental illness are seeking care in public hospital emergency departments. AIMS analysis highlights the importance of understanding the contributing and precipitating factors in violent incidents, and supports a variety of preventive initiatives, including de-escalation training for staff; violence management plans; improved building design to protect staff and patients; and fast-tracking of patients with mental health problems as well as improved waiting times in public hospital emergency services. We recommend that a national system be developed to share and compare incident monitoring data, to monitor trends, and to facilitate learning and thinking at all levels - ward, department, hospital, state and national.Klee A Benveniste, Peter D Hibbert and William B Runcima

Fractional dynamics pharmacokinetics–pharmacodynamic models

While an increasing number of fractional order integrals and differential equations applications have been reported in the physics, signal processing, engineering and bioengineering literatures, little attention has been paid to this class of models in the pharmacokinetics–pharmacodynamic (PKPD) literature. One of the reasons is computational: while the analytical solution of fractional differential equations is available in special cases, it this turns out that even the simplest PKPD models that can be constructed using fractional calculus do not allow an analytical solution. In this paper, we first introduce new families of PKPD models incorporating fractional order integrals and differential equations, and, second, exemplify and investigate their qualitative behavior. The families represent extensions of frequently used PK link and PD direct and indirect action models, using the tools of fractional calculus. In addition the PD models can be a function of a variable, the active drug, which can smoothly transition from concentration to exposure, to hyper-exposure, according to a fractional integral transformation. To investigate the behavior of the models we propose, we implement numerical algorithms for fractional integration and for the numerical solution of a system of fractional differential equations. For simplicity, in our investigation we concentrate on the pharmacodynamic side of the models, assuming standard (integer order) pharmacokinetics

Spin chemistry investigation of peculiarities of photoinduced electron transfer in donor-acceptor linked system

Photoinduced intramolecular electron transfer in linked systems, (R,S)- and (S,S)-naproxen-N-methylpyrrolidine dyads, has been studied by means of spin chemistry methods [magnetic field effect and chemically induced dynamic nuclear polarization (CIDNP)]. The relative yield of the triplet state of the dyads in different magnetic field has been measured, and dependences of the high-field CIDNP of the N-methylpyrrolidine fragment on solvent polarity have been investigated. However, both (S,S)- and (R,S)-enantiomers demonstrate almost identical CIDNP effects for the entire range of polarity. It has been demonstrated that the main peculiarities of photoprocesses in this linked system are connected with the participation of singlet exciplex alongside with photoinduced intramolecular electron transfer in chromophore excited state quenching.This work was supported by the grants 08-03-00372 and 11-03-01104 of the Russian Foundation for Basic Research, and the grant of Priority Programs of the Russian Academy of Sciences, nr. 5.1.5.Magin, I.; Polyakov, N.; Khramtsova, E.; Kruppa, A.; Stepanov, A.; Purtov, P.; Leshina, T.... (2011). Spin chemistry investigation of peculiarities of photoinduced electron transfer in donor-acceptor linked system. Applied Magnetic Resonance. 41(2-4):205-220. https://doi.org/10.1007/s00723-011-0288-3S205220412-4J.S. Park, E. Karnas, K. Ohkubo, P. Chen, K.M. Kadish, S. Fukuzumi, C.W. Bielawski, T.W. Hudnall, V.M. Lynch, J.L. Sessler, Science 329, 1324–1327 (2010)S.Y. Reece, D.G. Nocera, Annu. Rev. Biochem. 78, 673–699 (2009)M.S. Afanasyeva, M.B. Taraban, P.A. Purtov, T.V. Leshina, C.B. Grissom, J. Am. Chem. Soc. 128, 8651–8658 (2006)M.A. Fox, M. Chanon, in Photoinduced Electron Transfer. C: Photoinduced Electron Transfer Reactions: Organic Substrates (Elsevier, New York, 1988), p. 754P.J. Hayball, R.L. Nation, F. Bochner, Chirality 4, 484–487 (1992)N. Suesa, M.F. Fernandez, M. Gutierrez, M.J. Rufat, E. Rotllan, L. Calvo, D. Mauleon, G. Carganico, Chirality 5, 589–595 (1993)A.M. Evans, J. Clin. Pharmacol. 36, 7–15 (1996)Y. Inoue, T. Wada, S. Asaoka, H. Sato, J.-P. Pete, Chem Commun. 4, 251–259 (2000)T. Yorozu, K. Hayashi, M. Irie, J. Am. Chem. Soc. 103, 5480–5548 (1981)N.J. Turro, in Modern Molecular Photochemistry (Benjamin/Cummings, San Francisco, 1978)K.M. Salikhov, Y.N. Molin, R.Z. Sagdeev, A.L. Buchachenko, in Spin Polarization and Magnetic Field Effects in Radical Reactions (Akademiai Kiado, Budapest, 1984), p. 419E.A. Weiss, M.A. Ratner, M.R. Wasielewski, J. Phys. Chem. A 107, 3639–3647 (2003)A.S. Lukas, P.J. Bushard, E.A. Weiss, M.R. Wasielewski, J. Am. Chem. Soc. 125, 3921–3930 (2003)R. Nakagaki, K. Mutai, M. Hiramatsu, H. Tukada, S. Nakakura, Can. J. Chem. 66, 1989–1996 (1988)M.C. Jim′enez, U. Pischel, M.A. Miranda, J. Photochem. Photobiol. C Photochem. Rev. 8, 128–142 (2007)S. Abad, U. Pischel, M.A. Miranda, Photochem. Photobiol. Sci. 4, 69–74 (2005)U. Pischel, S. Abad, L.R. Domingo, F. Bosca, M.A. Miranda, Angew. Chem. Int. Ed. 42, 2531–2534 (2003)G.L. Closs, R.J. Miller, J. Am. Chem. Soc. 101, 1639–1641 (1979)G.L. Closs, R.J. Miller, J. Am. Chem. Soc. 103, 3586–3588 (1981)M. Goez, Chem. Phys. Lett. 188, 451–456 (1992)I.F. Molokov, Y.P. Tsentalovich, A.V. Yurkovskaya, R.Z. Sagdeev, J. Photochem. Photobiol. A 110, 159–165 (1997)U. Pischel, S. Abad, M.A. Miranda, Chem. Commun. 9, 1088–1089 (2003)H. Hayashi, S. Nagakura, Bull. Chem. Soc. Jpn. 57, 322–328 (1984)Y. Sakaguchi, H. Hayashi, S. Nagakura, Bull. Chem. Soc. Jpn. 53, 39–42 (1980)H. Yonemura, H. Nakamura, T. Matsuo, Chem. Phys. Lett. 155, 157–161 (1989)N. Hata, M. Hokawa, Chem. Lett. 10, 507–510 (1981)M. Shiotani, L. Sjoeqvist, A. Lund, S. Lunell, L. Eriksson, M.B. Huang, J. Phys. Chem. 94, 8081–8090 (1990)E. Schaffner, H. Fischer, J. Phys. Chem. 100, 1657–1665 (1996)Y. Mori, Y. Sakaguchi, H. Hayashi, Chem. Phys. Lett. 286, 446–451 (1998)I.M. Magin, A.I. Kruppa, P.A. Purtov, Chem. Phys. 365, 80–84 (2009)K.K. Barnes, Electrochemical Reactions in Nonaqueous Systems (M. Dekker, New York, 1970), p. 560J. Bargon, J. Am. Chem. Soc. 99, 8350–8351 (1977)M. Goez, I. Frisch, J. Phys. Chem. A 106, 8079–8084 (2002)A.K. Chibisov, Russ. Chem. Rev. 50, 615–629 (1981)J. Goodman, K. Peters, J. Am. Chem. Soc. 107, 1441–1442 (1985)H. Cao, Y. Fujiwara, T. Haino, Y. Fukazawa, C.-H. Tung, Y. Tanimoto, Bull. Chem. Soc. Jpn. 69, 2801–2813 (1996)P.A. Purtov, A.B. Doktorov, Chem. Phys. 178, 47–65 (1993)A.I. Kruppa, O.I. Mikhailovskaya, T.V. Leshina, Chem. Phys. Lett. 147, 65–71 (1988)M.E. Michel-Beyerle, R. Haberkorn, W. Bube, E. Steffens, H. Schröder, H.J. Neusser, E.W. Schlag, H. Seidlitz, Chem. Phys. 17, 139–145 (1976)K. Schulten, H. Staerk, A. Weller, H.-J. Werner, B. Nickel, Z. Phys. Chem. 101, 371–390 (1976)K. Gnadig, K.B. Eisenthal, Chem. Phys. Lett. 46, 339–342 (1977)T. Nishimura, N. Nakashima, N. Mataga, Chem. Phys. Lett. 46, 334–338 (1977)M.G. Kuzmin, I.V. Soboleva, E.V. Dolotova, D.N. Dogadkin, High Eng. Chem. 39, 86–96 (2005

Distribution pattern of psoriasis, anxiety and depression as possible causes of sexual dysfunction in patients with moderate to severe psoriasis

BACKGROUND: Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relation. However, beyond genital psoriasis, the importance of the disease's distribution patterns has not been considered. OBJECTIVES: To research sexual function in psoriasis patients and investigate the roles of anxiety, depression and psoriasis' distribution patterns in sexual dysfunction. METHODS: A comparative study matched for sex and age was performed. Eighty patients with moderate to severe psoriasis and 80 healthy controls were included. The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index. RESULTS: Psoriasis was associated with sexual dysfunction, odds ratio=5.5 (CI 95% 2.6-11.3; p<0.001). Certain distribution patterns of psoriasis, involving specific body regions, were associated with an increase in sexual dysfunction in the group presenting the disease, odds ratio 7.9 (CI 95% 2.3-33.4; p<0.001). Multivariate logistic regression analysis identified anxiety and depression, and the involvement of these specific areas, as possible independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis. CONCLUSION: This study identifies body areas potentially related to sexual dysfunction, independently of anxiety and depression, in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when choosing the treatment for psoriasis patients

Neural Stem Cells Achieve and Maintain Pluripotency without Feeder Cells

Background: Differentiated cells can be reprogrammed into pluripotency by transduction of four defined transcription factors. Induced pluripotent stem cells (iPS cells) are expected to be useful for regenerative medicine as well as basic research. Recently, the report showed that mouse embryonic fibroblasts (MEF) cells are not essential for reprogramming. However, in using fibroblasts as donor cells for reprogramming, individual fibroblasts that had failed to reprogram could function as feeder cells. Methodology/Principal Finding: Here, we show that adult mouse neural stem cells (NSCs), which are not functional feeder cells, can be reprogrammed into iPS cells using defined four factors (Oct4, Sox2, Klf4, and c-Myc) under feeder-free conditions. The iPS cells, generated from NSCs expressing the Oct4-GFP reporter gene, could proliferate for more than two months (passage 20). Generated and maintained without feeder cells, these iPS cells expressed pluripotency markers (Oct4 and Nanog), the promoter regions of Oct4 and Nanog were hypomethylated, could differentiated into to all three germ layers in vitro, and formed a germline chimera. These data indicate that NSCs can achieve and maintain pluripotency under feeder-free conditions. Conclusion/Significance: This study suggested that factors secreted by feeder cells are not essential in the initial/early stages of reprogramming and for pluripotency maintenance. This technology might be useful for a human system, as

In vitro generation of neuromesodermal progenitors reveals distinct roles for wnt signalling in the specification of spinal cord and paraxial mesoderm identity

Cells of the spinal cord and somites arise from shared, dual-fated precursors, located towards the posterior of the elongating embryo. Here we show that these neuromesodermal progenitors (NMPs) can readily be generated in vitro from mouse and human pluripotent stem cells by activating Wnt and Fgf signalling, timed to emulate in vivo development. Similar to NMPs in vivo, these cells co-express the neural factor Sox2 and the mesodermal factor Brachyury and differentiate into neural and paraxial mesoderm in vitro and in vivo. The neural cells produced by NMPs have spinal cord but not anterior neural identity and can differentiate into spinal cord motor neurons. This is consistent with the shared origin of spinal cord and somites and the distinct ontogeny of the anterior and posterior nervous system. Systematic analysis of the transcriptome during differentiation identifies the molecular correlates of each of the cell identities and the routes by which they are obtained. Moreover, we take advantage of the system to provide evidence that Brachyury represses neural differentiation and that signals from mesoderm are not necessary to induce the posterior identity of spinal cord cells. This indicates that the mesoderm inducing and posteriorising functions of Wnt signalling represent two molecularly separate activities. Together the data illustrate how reverse engineering normal developmental mechanisms allows the differentiation of specific cell types in vitro and the analysis of previous difficult to access aspects of embryo development

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family