452 research outputs found

    Testing feasibility of relevant outcome measures in an inpatient setting to demonstrate the value of occupational therapy

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    Introduction Measures of participation restrictions in daily life occupations are not typically used and may aid discharge planning and demonstrate the impact of occupational therapy services in inpatient settings. The overall aim of this mixed-methods study was to test the feasibility of relevant outcome measures by (1) investigating which of the three identified measures—the Home Support Needs Assessment, the Personal Care Participation Assessment and Resource Tool, and the Functional Autonomy Measurement System—best identifies meaningful changes in participation restrictions in daily life occupations required for community life; and (2) investigating the acceptability, usefulness, and feasibility of each measure to support inpatient practice. Methods Occupational therapists (n = 3) completed the three measures with patient participants (n = 12) at admission and discharge. Each occupational therapist participated in a semi-structured interview. Outcome measure responses were summarised statistically. Qualitative data were analysed using reflexive thematic analysis. Findings Total scores on all three measures changed significantly between admission and discharge (P < 0.002). Three themes reflected the occupational therapist participants' perceptions of the acceptability, usefulness, and feasibility of the outcome measures: ‘Clinically and Professionally Meaningful Tools’, ‘Becoming Familiar’, and ‘Fostering My Daily Work’. Conclusion Each measure demonstrated a meaningful change. Selection and successful implementation of an outcome measure depends on its local acceptability to occupational therapists and organisational practices. All three measures are promising tools to address a measurement gap in occupational therapy practice. Future research could embed one measure into practice using knowledge translation methods, with a large-scale evaluation of the value of occupational therapy

    Regionally acquired intestinal failure data suggest an underestimate in national service requirements

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    Objectives, setting and patients: With complete case referral for prolonged parenteral nutrition (PN) beyond term equivalent, serving a stable population of 1.25 million people, we describe the long-term outcome and survival of patients referred to an intestinal failure (IF) nutrition support team over the first 8 years of existence at a regional paediatric centre, and extrapolate to potential numbers of national home parenteral nutrition (HPN) cases and intestinal transplantation data. Design and outcome measures: Retrospective analysis detailing patient demographics, interventions, use of HPN, occurrence of intestinal failure-associated liver disease (IFALD), and outcomes of enteral adaptation, survival, and referral for and receipt of organ transplantation. Results: 23 patients were referred over 8 years, 20 being PN dependent within the neonatal period. Diagnoses included short bowel syndrome (SBS) (18), neuromuscular abnormalities (4) and congenital enterocyte disorder (1). 12 696 days of PN were delivered with 314 confirmed episodes of sepsis at a median of 12 episodes per patient. 144 central venous catheters (CVCs) were required at a median of four per patient. IFALD occurred in 17 (73%) patients, with 10 (44%) referred for transplant assessment. Thirteen (56%) children received HPN. Overall mortality was 44%. A significant predictor for survival in the SBS group was residual bowel >40 cm (82% vs 28%, p = 0.049). Conclusions: Survival for IF at 56% was lower than reported from non-UK supra-regional centres, and nationally collected data, possibly reflecting pre-selected referral populations. Data from regional centres with complete ascertainment may be important both when counselling parents and when planning regional and national HPN and IF specialist services

    Communicative focus on form and second language suprasegmental learning: teaching Cantonese learners to perceive mandarin tones

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    The current study examined how form-focused instruction (FFI) with and without corrective feedback (CF) as output enhancement can facilitate L2 perception of Mandarin tones at both the phonetic and phonological levels in 41 Cantonese learners of Mandarin. Two experimental groups, FFI-only and FFI-CF, received a 90-minute FFI treatment designed to encourage them to notice and practice the categorical distinctions of Mandarin tones through a range of communicative input and output activities. During these activities, the instructors provided CF only to students in the FFI-CF group by recasting and pushing them to repair their mispronunciations of the target features (i.e., output enhancement). The control group received comparable meaning-oriented instruction without any FFI. The effectiveness of FFI was assessed via a forced-choice identification task with both trained and untrained items for a variety of tonal contrasts in Mandarin (high level Tone 1 vs. mid-rising Tone 2 vs. high falling Tone 4). According to statistical comparisons, the FFI-only group attained significant improvement in all lexical and tonal contexts, and such effectiveness was evident particularly in the acquisition of Tone 1 and Tone 4—supposedly the most difficult instances due to their identical phonological status in the learners’ L1, Cantonese. The FFI-CF group, however, demonstrated marginally significant gains only under the trained lexical conditions. The results in turn suggest that FFI promotes learners’ attentional shift from vocabulary to sound learning (generalizable gains in trained and untrained items) and facilitates their access to new phonetic and phonological categories. Yet, the relative advantage of adding CF to FFI as output enhancement remains unclear, especially with respect to the less experienced L2 learners in the current study

    Systematic review of the clinical effectiveness and cost-effectiveness and economic modelling of minimal incision total hip replacement approaches in the management of arthritic disease of the hip

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    Objectives: To assess the clinical effectiveness and cost-effectiveness of minimal incision approaches to total hip replacement (THR) for arthritis of the hip. Data sources: Major electronic databases were searched from 1966 to 2007. Relevant websites were also examined and experts in the field were consulted. Review methods: Studies of minimal (one or two) incision THR compared with standard THR were assessed for inclusion in the review of clinical effectiveness. A systematic review of economic evaluations comparing a minimal incision approach to standard THR was also performed and the estimates from the systematic review of clinical effectiveness were incorporated into an economic model. Utilities data were sourced to estimate quality-adjusted life-years (QALYs). Due to lack of data, no economic analysis was conducted for the two mini-incision surgical method. Results: Nine randomised controlled trials (RCTs), 17 non-randomised comparative studies, six case series and one registry were found to be useful for the comparison of single mini-incision THR with standard THR. One RCT compared two mini-incision THR with standard THR, and two RCTs, five non-randomised comparative studies and two case series compared two mini-incision with single mini-incision THR. The RCTs were of moderate quality. Most had fewer than 200 patients and had a follow-up period of less than 1 year. The single mini-incision THR may have some perioperative advantages, e.g. blood loss [weighted mean difference (WMD) –57.71 ml, p £30,000) if recovery was 1.5 weeks faster. A threshold analysis around risk of revision showed, using the same cost per QALY threshold, mini-incision THR would have to have no more than a 7.5% increase in revisions compared with standard THR for it to be no longer considered cost-effective (one more revision for every 200 procedures performed). Further sensitivity analysis involved relaxing assumptions of equal long-term outcomes where possible. and broadly similar results to the base-case analysis were found in this and further sensitivity analyses. Conclusions: Compared with standard THR, minimal incision THR has small perioperative advantages in terms of blood loss and operation time. It may offer a shorter hospital stay and quicker recovery. It appears to have a similar procedure cost to standard THR, but evidence on its longer term performance is very limited. Further long-term follow-up data on costs and outcomes including analysis of subgroups of interest to the NHS would strengthen the current economic evaluation.The Health Services Research Unit and the Health Economics Research Unit are both core funded by the Chief Scientist Office of the Scottish Government Health Directorates.Peer reviewedPublisher PD

    Challenges of Loss to Follow-up in Tuberculosis Research.

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    In studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and reasons for not attending were examined. In 160 children who attended and 102 children who did not attend scheduled 2-month follow-up baseline health characteristics, demographic data and risk factors for not attending follow-up were determined. Qualitative interviews were used to understand patient and caretakers reasons for not returning for scheduled follow-up. Being treated for active tb in the dots program (OR: 4.14; 95% CI:1.99-8.62;p-value<0.001) and receiving money for the bus fare (OR:129; 95% CI 16->100;P-value<0.001) were positive predictors for attending follow-up at 2 months, and 21/85(25%) of children not attending scheduled follow-up had died. Interviews revealed that limited financial resources, i.e. lack of money for transportation and poor communication, were related to non-adherence. Patients lost to follow-up is a potential problem for TB research. Receiving money for transportation to the hospital and communication is crucial for adherence to follow-up conducted at a study facility. Strategies to ensure follow-up should be part of any study protocol

    GABA transporter function, oligomerization state, and anchoring: correlates with subcellularly resolved FRET

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    The mouse γ-aminobutyric acid (GABA) transporter mGAT1 was expressed in neuroblastoma 2a cells. 19 mGAT1 designs incorporating fluorescent proteins were functionally characterized by [^3H]GABA uptake in assays that responded to several experimental variables, including the mutations and pharmacological manipulation of the cytoskeleton. Oligomerization and subsequent trafficking of mGAT1 were studied in several subcellular regions of live cells using localized fluorescence, acceptor photobleach Förster resonance energy transfer (FRET), and pixel-by-pixel analysis of normalized FRET (NFRET) images. Nine constructs were functionally indistinguishable from wild-type mGAT1 and provided information about normal mGAT1 assembly and trafficking. The remainder had compromised [^3H]GABA uptake due to observable oligomerization and/or trafficking deficits; the data help to determine regions of mGAT1 sequence involved in these processes. Acceptor photobleach FRET detected mGAT1 oligomerization, but richer information was obtained from analyzing the distribution of all-pixel NFRET amplitudes. We also analyzed such distributions restricted to cellular subregions. Distributions were fit to either two or three Gaussian components. Two of the components, present for all mGAT1 constructs that oligomerized, may represent dimers and high-order oligomers (probably tetramers), respectively. Only wild-type functioning constructs displayed three components; the additional component apparently had the highest mean NFRET amplitude. Near the cell periphery, wild-type functioning constructs displayed the highest NFRET. In this subregion, the highest NFRET component represented ~30% of all pixels, similar to the percentage of mGAT1 from the acutely recycling pool resident in the plasma membrane in the basal state. Blocking the mGAT1 C terminus postsynaptic density 95/discs large/zona occludens 1 (PDZ)-interacting domain abolished the highest amplitude component from the NFRET distributions. Disrupting the actin cytoskeleton in cells expressing wild-type functioning transporters moved the highest amplitude component from the cell periphery to perinuclear regions. Thus, pixel-by-pixel NFRET analysis resolved three distinct forms of GAT1: dimers, high-order oligomers, and transporters associated via PDZ-mediated interactions with the actin cytoskeleton and/or with the exocyst

    A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability

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    43 p.-5 fig.Despite the approval of several multikinase inhibitors that target SRC and the overwhelming evidence of the role of SRC in the progression and resistance mechanisms of many solid malignancies, inhibition of its kinase activity has thus far failed to improve patient outcomes. Here we report the small molecule eCF506 locks SRC in its native inactive conformation, thereby inhibiting both enzymatic and scaffolding functions that prevent phosphorylation and complex formation with its partner FAK. This unprecedented mechanism of action resulted in highly potent and selective pathway inhibition, in culture and in vivo. Treatment with eCF506 resulted in increased antitumor efficacy and tolerability in syngeneic murine cancer models, demonstrating significant therapeutic advantages over existing SRC/ABL inhibitors. Therefore, this novel mode of inhibiting SRC could lead to improved treatment of SRC-associated disorders.C.T. thanks the CMVM of the University of Edinburgh (Principal's scholarship). D.L. acknowledges support from the Spanish Ministry of Science, Innovation and Universities for the Spanish State Research Agency Retos Grant RTI2018-099318-B-I00, cofunded by the European Regional Development Fund (FEDER). E.R.W., J.C.D. and K.G.M. are funded by CRUK. J.R.L.O. acknowledges support from the Molecular Interactions Facility funds at the CIB-CSIC. T.V. is funded by H2020-MSCA-IF-2016-749299. RCM thanks the support from the Vice Rectorate for Research of the University of Granada. X.-F.L. and B.-Z.Q. are funded by a CRUK Career Development Fellowship (C49791/A17367). B.-Z.Q. also acknowledges support from an ERC Starting Grant (716379). C.S, M.C.F. and V.G.B are funded by CRUK Programme Grant C157/A15703. N.O.C. and A.U.B are grateful to the CMVM of the University of Edinburgh and Wellcome Trust for financial support (ISSF3).Peer reviewe
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