Improving specialised care for neuromuscular patients reduces the frequency of preventable emergency hospital admissions

Two retrospective audits were undertaken across several hospitals to understand the frequency and preventability of emergency admissions in people with neuromuscular disease (NMD). Following audit 1 (A1), a number of preventable themes emerged on the basis of which recommendations were made to improve quality and co-ordination of care and a network approach was developed to improve awareness and education amongst patients and non-expert professionals. Audit 2 (A2) was undertaken to determine the effect of these measures. The central NHS IT database identified emergency NMD admissions. Case notes were reviewed and audited against pre-agreed criteria. A1 included 576 admissions (395 patients) A2 included 361 admissions (314 patients). Preventable admissions (where an NMD was known) accounted for 63% in A1 and 33% in A2, with more patients followed up at a specialized neuromuscular centre in A2. There were fewer re-admissions in A2 (12%) compared with A1 (25%) and lower mortality (A1: 4.5%, A2: 0.3%). A2 showed a significant rise in patients admitted under the care of neuroscience during the acute admission and fewer preventable ITU admissions. These audits demonstrate a significant impact for both patient care and potential for financial savings following the implementation of recommendations made after A1

Development and implementation of the Structured Training Trainer Assessment Report (STTAR) in the English National Training Programme for laparoscopic colorectal surgery

Background: There is a lack of educational tools available for surgical teaching critique, particularly for advanced laparoscopic surgery. The aim was to develop and implement a tool that assesses training quality and structures feedback for trainers in the English National Training Programme for laparoscopic colorectal surgery. Methods: Semi-structured interviews were performed and analysed, and items were extracted. Through the Delphi process, essential items pertaining to desirable trainer characteristics, training structure and feedback were determined. An assessment tool (Structured Training Trainer Assessment Report—STTAR) was developed and tested for feasibility, acceptability and educational impact. Results: Interview transcripts (29 surgical trainers, 10 trainees, four educationalists) were analysed, and item lists created and distributed for consensus opinion (11 trainers and seven trainees). The STTAR consisted of 64 factors, and its web-based version, the mini-STTAR, included 21 factors that were categorised into four groups (training structure, training behaviour, trainer attributes and role modelling) and structured around a training session timeline (beginning, middle and end). The STTAR (six trainers, 48 different assessments) demonstrated good internal consistency (α = 0.88) and inter-rater reliability (ICC = 0.75). The mini-STTAR demonstrated good inter-item reliability (α = 0.79) and intra-observer reliability on comparison of 85 different trainer/trainee combinations (r = 0.701, p = <0.001). Both were found to be feasible and acceptable. The educational report for trainers was found to be useful (4.4 out of 5). Conclusions: An assessment tool that evaluates training quality was developed and shown to be reliable, acceptable and of educational value. It has been successfully implemented into the English National Training Programme for laparoscopic colorectal surgery

HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-25% of breast cancers, usually as a result of HER2 gene amplification. Positive HER2 status is considered to be an adverse prognostic factor. Recognition of the role of HER2 in breast cancer growth has led to the development of anti-HER2 directed therapy, with the humanized monoclonal antibody trastuzumab (Herceptin (R)) having been approved for the therapy of HER2-positive metastatic breast cancer. Clinical studies have further suggested that HER2 status can provide important information regarding success or failure of certain hormonal therapies or chemotherapies. As a result of these developments, there has been increasing demand to perform HER2 testing on current and archived breast cancer specimens. This article reviews the molecular background of HER2 function, activation and inhibition as well as current opinions concerning its role in chemosensitivity and interaction with estrogen receptor biology. The different tissue-based assays used to detect HER2 amplification and overexpression are discussed with respect to their advantages and disadvantages, when to test (at initial diagnosis or pre-treatment), where to test (locally or centralized) and the need for quality assurance to ensure accurate and valid testing results

Shape-induced force fields in optical trapping

Advances in optical tweezers, coupled with the proliferation of two-photon polymerization systems, mean that it is now becoming routine to fabricate and trap non-spherical particles. The shaping of both light beams and particles allows fine control over the flow of momentum from the optical to mechanical regimes. However, understanding and predicting the behaviour of such systems is highly complex in comparison with the traditional optically trapped microsphere. In this Article, we present a conceptually new and simple approach based on the nature of the optical force density. We illustrate the method through the design and fabrication of a shaped particle capable of acting as a passive force clamp, and we demonstrate its use as an optically trapped probe for imaging surface topography. Further applications of the design rules highlighted here may lead to new sensors for probing biomolecule mechanics, as well as to the development of optically actuated micromachines

Differential phenotypic expression of a novel PDHA1 mutation in a female monozygotic twin pair

Pyruvate dehydrogenase complex (PDC) deficiency caused by mutations in the X-linked PDHA1 gene has a broad clinical presentation, and the pattern of X-chromosome inactivation has been proposed as a major factor contributing to its variable expressivity in heterozygous females. Here, we report the first set of monozygotic twin females with PDC deficiency, caused by a novel, de novo heterozygous missense mutation in exon 11 of PDHA1 (NM_000284.3: c.1100A>T). Both twins presented in infancy with a similar clinical phenotype including developmental delay, episodes of hypotonia or encephalopathy, epilepsy, and slowly progressive motor impairment due to pyramidal, extrapyramidal, and cerebellar involvement. However, they exhibited clear differences in disease severity that correlated well with residual PDC activities (approximately 60% and 20% of mean control values, respectively) and levels of immunoreactive E1α subunit in cultured skin fibroblasts. To address whether the observed clinical and biochemical differences could be explained by the pattern of X-chromosome inactivation, we undertook an androgen receptor assay in peripheral blood. In the less severely affected twin, a significant bias in the relative activity of the two X chromosomes with a ratio of approximately 75:25 was detected, while the ratio was close to 50:50 in the other twin. Although it may be difficult to extrapolate these results to other tissues, our observation provides further support to the hypothesis that the pattern of X-chromosome inactivation may influence the phenotypic expression of the same mutation in heterozygous females and broadens the clinical and genetic spectrum of PDC deficiency

Do Basic Psychomotor Skills Transfer Between Different Image-based Procedures?

Background - Surgical techniques that draw from multiple types of image-based procedures (IBP) are increasing, such as Natural Orifice Transluminal Endoscopic Surgery, fusing laparoscopy and flexible endoscopy. However, little is known about the relation between psychomotor skills for performing different types of IBP. For example, do basic psychomotor colonoscopy and laparoscopy skills interact? Methods - Following a cross-over study design, 29 naïve endoscopists were trained on the Simbionix GI Mentor and the SimSurgery SEP simulators. Group C (n = 15) commenced with a laparoscopy session, followed by four colonoscopy sessions and a second laparoscopy session. Group L (n = 14) started with a colonoscopy session, followed by four laparoscopy sessions and a second colonoscopy session. Results - No significant differences were found between the performances of group L and group C in their first training sessions on either technique. With additional colonoscopy training, group C outperformed group L in the second laparoscopy training session on the camera navigation task. Conclusions - Overall, training in the basic colonoscopy tasks does not affect performance of basic laparoscopy tasks (and vice versa). However, to limited extent, training of basic psychomotor skills for colonoscopy do appear to contribute to the performance of angled laparoscope navigation tasks. Thus, training and assessment of IBP typespecific skills should focus on each type of tasks independently. Future research should further investigate the influence of psychometric abilities on the performance of IBP and the transfer of skills for physicians who are experienced in one IBP type and would like to become proficient in another type of IBP.Industrial DesignIndustrial Design Engineerin

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing