Demands on publicly funded ophthalmic services worldwide continue to increase with new treatments, waiting time targets, working time limits, and restricted budgets. These highlight the necessity to ...develop innovative ways of utilising existing capacity more effectively.
A new regional, fully electronic ophthalmic-referral service with digital imaging was trialled using existing information-technology (IT) infrastructure. Following successful pilot study, the service was rolled out regionally. Service delivery data was prospectively collated for all the attendances in the year prior to (2006) and the year following (2008) introduction.
Comparing 2006 against 2008, median waiting times reduced (14 vs 4 weeks), and fewer new patients were observed (8714 vs 7462 P<0.0001), with 1359 referrals receiving electronic diagnosis (e-diagnosis). New patient did not arrive (635 vs 503 P<0.0001) and emergencies also reduced (2671 v 1984 P<0.0001).
Novel use of existing IT infrastructure improves communication between primary and secondary care. This promotes more effective use of limited outpatient capacity by retaining patients with non-progressive, asymptomatic pathology in the community, whilst fast-tracking patients with sight-threatening disease. Resultant significant, sustained improvements in regional service delivery point to a simple model that could easily be adopted by other providers of universal healthcare globally.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objective
The best screening questionnaires for detecting post-stroke depression have not been identified. We aimed to validate four commonly used depression screening tools in stroke and transient ...ischemic attack patients.
Methods
Consecutive stroke and transient ischemic attack patients visiting an outpatient stroke clinic in Calgary, Alberta (Canada) completed a demographic questionnaire and four depression screening tools: Patient Health Questionnaire (PHQ)-9, PHQ-2, Hospital Anxiety and Depression Scale (HADS-D), and Geriatric Depression Scale (GDS-15). Participants then completed the Structured Clinical Interview for DSM-IV (SCID), the gold-standard for diagnosing major depression. The questionnaires were validated against the SCID and sensitivity and specificity were calculated at various cut-points. Optimal cut-points for each questionnaire were determined using receiver-operating curve analyses.
Results
Among 122 participants, 59.5% were diagnosed with stroke and 40.5% with transient ischemic attack. The point prevalence of SCID-diagnosed current major depression was 9.8%. At the optimal cut-points, the sensitivity and specificity for each screening tool were as follows: PHQ-9 (sensitivity: 81.8%, specificity: 97.1%), PHQ-2 (sensitivity: 75.0%, specificity: 96.3%), HADS-D (sensitivity: 63.6%, specificity: 98.1%), and GDS-15 (sensitivity: 45.5%, specificity: 84.8%). Areas under the receiver operating characteristic curves were as follows: PHQ-9 86.6%, PHQ-2 86.7%, HADS-D 85.9%, and GDS-15 66.3%.
Conclusions
The PHQ-2 and PHQ-9 are both suitable depression screening tools, taking less than 5 minutes to complete. The HADS-D does not appear to have any advantage over the PHQ-based scales, even though it was designed specifically for medically ill populations. The GDS-15 cannot be recommended for general use in a stroke clinic based on this study as it had worse discrimination due to low sensitivity.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Shc is a ubiquitously expressed Src homology 2 (SH2) domain protein that can transform fibroblasts and differentiate PC12
cells in a Ras-dependent fashion. Shc binds a variety of ...tyrosine-phosphorylated growth factor receptors presumably via its
carboxyl-terminal SH2 domain. We cloned a fragment of Shc when screening a bacterial expression library with tyrosine-phosphorylated
epidermal growth factor (EGF) receptor. Surprisingly, this fragment encodes the amino terminus of Shc, a region that has no
significant similarity to an SH2 domain. When expressed as a glutathione S-transferase fusion protein, this amino-terminal
domain binds to autophosphorylated EGF receptor, as well as HER2/neu and TrkA receptors. This fragment acts like an SH2 domain
in that it does not bind non-phosphorylated EGF receptor or EGF receptor with all tyrosine phosphorylation sites mutated or
deleted. Our data define a novel domain in Shc that has the potential to interact with growth factor receptors and other tyrosine-phosphorylated
proteins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In addition to tyrosine phosphorylation of the 66-, 52-, and 46-kDa Shc isoforms, epidermal growth factor (EGF) treatment of Chinese hamster ovary cells expressing the human EGF receptor also ...resulted in the serine/threonine phosphorylation of approximately 50% of the 66-kDa Shc proteins. The serine/threonine phosphorylation occurred subsequent to tyrosine phosphorylation and was prevented by pretreatment of the cells with the MEK-specific inhibitor PD98059. Surprisingly, only the gel-shifted 66-kDa Shc isoform (serine/threonine phosphorylated) was tyrosine phosphorylated and associated with Grb2. In contrast, only the non-serine/threonine-phosphorylated fraction of 66-kDa Shc was associated with the EGF receptor. To assess the relationship between the three Shc isoforms in EGF-stimulated signaling, the cDNA encoding the 66-kDa Shc species was cloned from a 16-day-old mouse embryo library. Sequence alignment confirmed that the 66-kDa Shc cDNA resulted from alternative splicing of the primary Shc transcript generating a 110-amino acid extension at the amino terminus. Co-immunoprecipitation of Shc and Grb2 from cells overexpressing the 52/46-kDa Shc isoforms versus the 66-kDa Shc species directly demonstrated a competition of binding for a limited pool of Grb2 proteins. Furthermore, expression of the 66-kDa Shc isoform markedly accelerated the inactivation of ERK following EGF stimulation. Together, these data indicate that the serine/threonine phosphorylation of 66-kDa Shc impairs its ability to associate with the tyrosine-phosphorylated EGF receptor and can function in a dominant-interfering manner by inhibiting EGF receptor downstream signaling pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives:
There is a lack of clear guidance regarding the management of ongoing suicidality in young people experiencing major depressive disorder. This study utilised an expert consensus approach ...in identifying practice principles to complement relevant clinical guidelines for the treatment of major depressive disorder in young people. The study also sought to outline a broad treatment framework for clinical intervention with young people experiencing ongoing suicidal ideation.
Methods:
In-depth focus groups were undertaken with a specialist multidisciplinary clinical team (the Youth Mood Clinic at Orygen Youth Health Clinical Program, Melbourne) working with young people aged 15–25 years experiencing ongoing suicidal ideation. Each focus group was audio recorded and transcribed verbatim using orthographic conventions. Principles of grounded theory and thematic analysis were used to analyse and code the resultant data.
Results:
The identified codes were subsequently synthesised into eight practice principles reflecting engagement and consistency of care, ongoing risk assessment and documentation, individualised crisis planning, engaging systems of support, engendering hopefulness, development of adaptive coping, management of acute risk, and consultation and supervision.
Conclusions:
The identified practice principles provide a broad management framework, and may assist to improve treatment consistency and clinical management of young people experiencing ongoing suicidal ideation. The practice principles may be of use to health professionals working within a team-based setting involved in the provision of care, even if peripherally, to young people with ongoing suicidal ideation. Findings address the lack of treatment consistency and shared terminology and may provide containment and guidance to multidisciplinary clinicians working with this at-risk group.
Patients with neurologic conditions commonly have depression. Online tools have the potential to improve outcomes in these patients in an efficient and accessible manner. We aimed to identify ...evidence-informed online tools for patients with comorbid neurologic conditions and depression.
A scoping review of online tools (free, publicly available, and not requiring a facilitator) for patients with depression and epilepsy, Parkinson disease (PD), multiple sclerosis (MS), traumatic brain injury (TBI), or migraine was conducted. MEDLINE, EMBASE, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL Register of Controlled Trials were searched from database inception to January 2017 for all 5 neurologic conditions. Gray literature using Google and Google Scholar as well as app stores for both Android and Apple devices were searched. Self-management or self-efficacy online tools were not included unless they were specifically targeted at depression and one of the neurologic conditions and met the other eligibility criteria.
Only 4 online tools were identified. Of these 4 tools, 2 were web-based self-management programs for patients with migraine or MS and depression. The other 2 were mobile apps for patients with PD or TBI and depression. No online tools were found for epilepsy.
There are limited depression tools for people with neurologic conditions that are evidence-informed, publicly available, and free. Future research should focus on the development of high-quality, evidence-based online tools targeted at neurologic patients.
Shc is an adaptor protein that contains two phosphotyrosine-binding domains, a Src homology 2 (SH2) domain and the newly described phosphotyrosine interaction (PI) domain. Shc interacts with several ...tyrosine-phosphorylated proteins and is itself tyrosine-phosphorylated in cells stimulated with a variety of growth factors and cytokines. Upon phosphorylation, Shc binds to the Grb2∙Sos complex leading to the activation of the Ras signaling pathway. Mutational analysis of the nerve growth factor (NGF) receptor (TrkA) suggested that the binding of Shc to the activated receptor is required for NGF-induced neuronal differentiation of PC12 cells. Here we report that the PI domain of Shc directly binds to tyrosine 490 on the autophosphorylated NGF receptor. The PI domain specifically recognizes an I/LXNPXpY motif (where p indicates phosphorylation) as determined by phosphopeptide competition assay. In addition, the PI domain is able to efficiently compete for binding of full-length Shc proteins to the NGF receptor. In PC12 cells, the Shc SH2 domain interacts with an unidentified tyrosine-phosphorylated protein of 115 kDa but not with the activated NGF receptor. The ability of Shc to interact with different tyrosine-phosphorylated proteins via its PI and SH2 domains may allow Shc to play a unique role in tyrosine kinase signal transduction pathways.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Skin‐sensitizing chemicals exhibit dose–response relationships for the elicitation of contact dermatitis. Previously, considerable work has been carried out in which the elicitation of allergic skin ...reaction has been examined as a function of the applied concentration. However, the relationship between exposure time, dose and response has not been explored in any depth. The present work has extended our initial assessment of the relationship between both exposure time and concentration for para‐phenylenediamine (PPD) in a group of 19 PPD‐allergic volunteers. The results clearly demonstrate that a relationship exists between both exposure time and concentration. Positive responses to PPD were directly proportional to exposure time: at 5 min 16% responded; at 15 min, 38%; at 30 min, 50%; and at 120 min, 69%. A similar direct relationship was found between concentration of PPD and response: after 120 min, 22% of patients had responded to 0.01%, and 69% to 1% PPD. All exposures for 1 and 2 min were negative. Subsequent evaluation using repeated 5 min open application testing demonstrated a cumulative effect, as after 8 days 39% of the panel reacted, more than double the number that reacted to a single occluded 5‐min treatment. It was noted that there was marked subject variability in exposure time and dose required to elicit an allergic response. These results are of relevance for the general interpretation of patch test data, especially with regard to risk assessment.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The phosphotyrosineinteraction (PI)/phosphotyrosinebinding (PTB) domain of Shc binds specific tyrosine-phosphorylated motifs found on activated growth factor receptors and proteins such as polyoma ...virus middle T antigen (MT). Phenylalanine 198 (Phe198) has been identified as a crucial residue involved in the interaction of the Shc PI/PTB with phosphopeptides. In NIH 3T3 cells expressing MT, p52 Shc carrying the F198V mutation is weakly phosphorylated and does not bind MT or Grb2. Overexpression of the PI/PTB domain alone as Shc amino acids 1–238 acted in a dominant interfering fashion blocking MT-induced transformation. However, expression of a slightly longer construct, Shc 1–260, which encompasses Tyr239/Tyr240, a novel Shc tyrosine phosphorylation site, did not block transformation. This was found to be due to the ability of Shc 1–260 to become tyrosine-phosphorylated and bind Grb2. Furthermore, full-length Shc in which Tyr239/Tyr240 had been mutated to phenylalanine did not become tyrosine-phosphorylated or bind Grb2 but did inhibit colony formation in soft agar. Conversely, p52 Shc carrying a mutation in the other tyrosine phosphorylation site, Tyr317, became heavily tyrosine-phosphorylated, bound Grb2, and gave rise to colonies in soft agar.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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