An Electronic Clinical Decision Support System for the Management of Low Back Pain in Community Pharmacy: Development and Mixed Methods Feasibility Study

Background People with low back pain (LBP) in the community often do not receive evidence-based advice and management. Community pharmacists can play an important role in supporting people with LBP as pharmacists are easily accessible to provide first-line care. However, previous research suggests that pharmacists may not consistently deliver advice that is concordant with guideline recommendations and may demonstrate difficulty determining which patients require prompt medical review. A clinical decision support system (CDSS) may enhance first-line care of LBP, but none exists to support the community pharmacist–client consultation. Objective This study aimed to develop a CDSS to guide first-line care of LBP in the community pharmacy setting and to evaluate the pharmacist-reported usability and acceptance of the prototype system. Methods A cross-platform Web app for the Apple iPad was developed in conjunction with academic and clinical experts using an iterative user-centered design process during interface design, clinical reasoning, program development, and evaluation. The CDSS was evaluated via one-to-one user-testing with 5 community pharmacists (5 case vignettes each). Data were collected via video recording, screen capture, survey instrument (system usability scale), and direct observation. Results Pharmacists’ agreement with CDSS-generated self-care recommendations was 90% (18/20), with medicines recommendations was 100% (25/25), and with referral advice was 88% (22/25; total 70 recommendations). Pharmacists expressed uncertainty when screening for serious pathology in 40% (10/25) of cases. Pharmacists requested more direction from the CDSS in relation to automated prompts for user input and page navigation. Overall system usability was rated as excellent (mean score 92/100, SD 6.5; 90th percentile compared with similar systems), with acceptance rated as good to excellent. Conclusions A novel CDSS (high-fidelity prototype) to enhance pharmacist care of LBP was developed, underpinned by clinical practice guidelines and informed by a multidisciplinary team of experts. User-testing revealed a high level of usability and acceptance of the prototype system, with suggestions to improve interface prompts and information delivery. The small study sample limits the generalizability of the findings but offers important insights to inform the next stage of system development. </jats:sec

HLA-E-restricted, Gag-specific CD8+ T cells can suppress HIV-1 infection, offering vaccine opportunities

Human leukocyte antigen-E (HLA-E) normally presents an HLA class Ia signal peptide to the NKG2A/C-CD94 regulatory receptors on natural killer (NK) cells and T cell subsets. Rhesus macaques immunized with a cytomegalovirus-vectored simian immunodeficiency virus (SIV) vaccine generated Mamu-E (HLA-E homolog)-restricted T cell responses that mediated post-challenge SIV replication arrest in >50% of animals. However, HIV-1-specific, HLA-E-restricted T cells have not been observed in HIV-1-infected individuals. Here, HLA-E-restricted, HIV-1-specific CD8 + T cells were primed in vitro. These T cell clones and allogeneic CD8 + T cells transduced with their T cell receptors suppressed HIV-1 replication in CD4 + T cells in vitro. Vaccine induction of efficacious HLA-E-restricted HIV-1-specific T cells should therefore be possible

Combining host and vector data informs emergence and potential impact of an Usutu virus outbreak in UK wild birds

Following the first detection in the United Kingdom of Usutu virus (USUV) in wild birds in 2020, we undertook a multidisciplinary investigation that combined screening host and vector populations with interrogation of national citizen science monitoring datasets to assess the potential for population impacts on avian hosts. Pathological findings from six USUV-positive wild passerines were non-specific, highlighting the need for molecular and immunohistochemical examinations to confirm infection. Mosquito surveillance at the index site identified USUV RNA in Culex pipiens s.l. following the outbreak. Although the Eurasian blackbird (Turdus merula) is most frequently impacted by USUV in Europe, national syndromic surveillance failed to detect any increase in occurrence of clinical signs consistent with USUV infection in this species. Furthermore, there was no increase in recoveries of dead blackbirds marked by the national ringing scheme. However, there was regional clustering of blackbird disease incident reports centred near the index site in 2020 and a contemporaneous marked reduction in the frequency with which blackbirds were recorded in gardens in this area, consistent with a hypothesis of disease-mediated population decline. Combining results from multidisciplinary schemes, as we have done, in real-time offers a model for the detection and impact assessment of future disease emergence events

A Morbidity Survey of South African Primary Care

Publication of this article was funded by the Stellenbosch University Open Access Fund.The original publication is available at www.plosone.org/BibliographyBackground: Recent studies have described the burden of disease in South Africa. However these studies do not tell us which of these conditions commonly present to primary care providers, how these conditions may present and how providers make sense of them in terms of their diagnoses. Clinical nurse practitioners are the main primary care providers and need to be better prepared for this role. This study aimed to determine the range and prevalence of reasons for encounter and diagnoses found among ambulatory patients attending public sector primary care facilities in South Africa. Methodology/Principal Findings: The study was a multi-centre prospective cross-sectional survey of consultations in primary care in four provinces of South Africa: Western Cape, Limpopo, Northern Cape and North West. Consultations were coded prior to analysis by using the International Classification of Primary Care-Version 2 in terms of reasons for encounter (REF) and diagnoses. Altogether 18856 consultations were included in the survey and generated 31451 reasons for encounter (RFE) and 24561 diagnoses. Women accounted for 12526 (66.6%) and men 6288 (33.4%). Nurses saw 16238 (86.1%) and doctors 2612 (13.9%) of patients. The top 80 RFE and top 25 diagnoses are reported and ongoing care for hypertension was the commonest RFE and diagnosis. The 20 commonest RFE and diagnoses by age group are also reported. Conclusions/Significance: Ambulatory primary care is dominated by non-communicable chronic diseases. HIV/AIDS and TB are common, but not to the extent predicted by the burden of disease. Pneumonia and gastroenteritis are commonly seen especially in children. Women’s health issues such as family planning and pregnancy related visits are also common. Injuries are not as common as expected from the burden of disease. Primary care providers did not recognise mental health problems. The results should guide the future training and assessment of primary care providers.Stellenbosch University Open Access FundPublishers' Versio

Identification of Stage-Specific Breast Markers using Quantitative Proteomics

YesMatched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.Cyprus Research Promotion Foundation, Yorkshire Cancer Researc

Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome

Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result in a virtual lack of glycosylation of α-dystroglycan. Compound heterozygous LARGE mutations have been reported in a single human patient, manifesting with mild congenital muscular dystrophy (CMD) and severe mental retardation. These mutations are likely to retain some residual LARGE glycosyltransferase activity as indicated by residual α-dystroglycan glycosylation in patient cells. We hypothesized that more severe LARGE mutations are associated with a more severe CMD phenotype in humans. Here we report a 63-kb intragenic LARGE deletion in a family with Walker-Warburg syndrome (WWS), which is characterized by CMD, and severe structural brain and eye malformations. This finding demonstrates that LARGE gene mutations can give rise to a wide clinical spectrum, similar as for other genes that have a role in the post-translational modification of the α-dystroglycan protein

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches

The humanistic roots of Islamic administration and leadership for education : philosophical foundations for cross-cultural and transcultural teaching

For a number of decades, a humanistic approach has been a minor but persistent one in the Western field of administrative and leadership studies, and only recently has been broadening to include other humanist traditions (Dierksmeier et al., 2011) and has yet to be fully explored in educational administration and its pedagogy and curriculum although some foundational work has been done (e.g., Samier, 2005). The focus in this chapter is on the Islamic humanist tradition as it relates to the teaching of educational administration and leadership in a Muslim context, with implications for cross-cultural and transcultural use. The second purpose of the chapter is to show the correspondences that exist between the Islamic and Western humanist traditions in terms of human values, knowledge and educational ideal, which in this chapter are argued to be close to the Western Idealist tradition and the German Bildung conception of education as well as the strong interpretive and hermeneutic foundations that originated in the Islamic tradition and which influenced the foundations of many relevant European schools of thought, particularly in the Enlightenment.The initial section of the chapter is a comparative examination of the central principles of the Islamic humanist tradition from the classical through to contemporary times with the Western humanist tradition as they relate to conceptions of the good, ethics, the construction of meaning and a set of higher order values predicated upon human dignity, integrity, empathy, well-being, and the public good (Goodman, 2003) covering a number of important scholars like Al Farabi, al Isfanhani, and Edward Said (e.g., Kraemer, 1986). In both, professions are viewed as meaningful work that allow for large measures of decision making, and are grounded in human qualities and needs including autonomy, freedom and emancipation balanced with responsibilities, obligations and duties to society. These are compared with the corresponding principles of knowledge in Western humanism which includes a strong constructivist view of reality (Makdisi, 1990). Secondly, the chapter examines the principles of good or ideal leadership and administration that humanism aims at in its preparation of officials, including those in the educational sector in both the classical Islamic tradition (Hassi, 2012) and Western approaches to humanistic administration and leadership (Czarniawska-Joerges & Guillet de Monthoux, 1994; Gagliardi & Czarniawska, 2006; Leoussi, 2000). The third section focusses on close correspondences that exist between the Islamic (Afsaruddin, 2016; al-Attas, 1980; Yasin & Jani, 2013) and Western (Aloni, 2007; Veugelers, 2011) humanist education traditions in terms of educational ideal as well as the kind of teaching practices that distinguish these traditions (Daiber, 2013; Dossett, 2014) as they apply to educational administration and leadership (Greenfield & Ribbins, 1993). The chapter concludes with a discussion of how the Islamic humanist tradition can contribute to cross-cultural and transcultural graduate teaching in international educational administration (Khan & Amann, 2013)