Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy.

Charcot neuroarthropathy is a rare but serious complication of diabetes, causing progressive destruction of the bones and joints of the foot leading to deformity, altered biomechanics and an increased risk of ulceration. Management is complicated by a lack of consensus on diagnostic criteria and an incomplete understanding of the pathogenesis. In this review, we consider recent insights into the development of Charcot neuroarthropathy. It is likely to be dependent on several interrelated factors which may include a genetic pre-disposition in combination with diabetic neuropathy. This leads to decreased neuropeptides (nitric oxide and calcitonin gene-related peptide), which may affect the normal coupling of bone formation and resorption, and increased levels of Receptor activator of nuclear factor kappa-B ligand, potentiating osteoclastogenesis. Repetitive unrecognized trauma due to neuropathy increases levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6, tumour necrosis factor α) which could also contribute to increased bone resorption, in combination with a pre-inflammatory state, with increased autoimmune reactivity and a profile of monocytes primed to transform into osteoclasts - cluster of differentiation 14 (CD14). Increased blood glucose and loss of circulating Receptor for Advanced Glycation End-Products (AGLEPs), leading to increased non-enzymatic glycation of collagen and accumulation of AGLEPs in the tissues of the foot, may also contribute to the pathological process. An understanding of the relative contributions of each of these mechanisms and a final common pathway for the development of Charcot neuroarthropathy are still lacking. Cite this article: S. E. Johnson-Lynn, A. W. McCaskie, A. P. Coll, A. H. N. Robinson. Neuroarthropathy in diabetes: pathogenesis of Charcot arthropathy. Bone Joint Res 2018;7:373-378. DOI: 10.1302/2046-3758.75.BJR-2017-0334.R1

Comparison of the Effectiveness of Transcutaneous Electrical Nerve Stimulation and Interferential Therapy on the Upper Trapezius in Myofascial Pain Syndrome: A Randomized Controlled Study.

OBJECTIVE: The aim of this study was to compare the effectiveness of transcutaneous electrical nerve stimulation and interferential therapy (IFT) both in combination with hot pack, myofascial release, active range of motion exercise, and a home exercise program on myofascial pain syndrome patients with upper trapezius myofascial trigger point. DESIGN: A total of 105 patients with an upper trapezius myofascial trigger point were recruited to this single-blind randomized controlled trial. Following random allocation of patients to three groups, three therapeutic regimens-control-standard care (hot pack, active range of motion exercises, myofascial release, and a home exercise program with postural advice), transcutaneous electrical nerve stimulation-standard care and IFT-standard care-were administered eight times during 4 wks at regular intervals. Pain intensity and cervical range of motions (cervical extension, lateral flexion to the contralateral side, and rotation to the ipsilateral side) were measured at baseline, immediately after the first treatment, before the eighth treatment, and 1 wk after the eighth treatment. RESULTS: Immediate and short-term improvements were marked in the transcutaneous electrical nerve stimulation group (n = 35) compared with the IFT group (n = 35) and the control group (n = 35) with respect to pain intensity and cervical range of motions (P < 0.05). The IFT group showed significant improvement on these outcome measurements than the control group did (P < 0.05). CONCLUSION: Transcutaneous electrical nerve stimulation with standard care facilitates recovery better than IFT does in the same combination

Expectancy changes the self-monitoring of voice identity

Self‐voice attribution can become difficult when voice characteristics are ambiguous, but functional magnetic resonance imaging (fMRI) investigations of such ambiguity are sparse. We utilized voice‐morphing (self‐other) to manipulate (un‐)certainty in self‐voice attribution in a button‐press paradigm. This allowed investigating how levels of self‐voice certainty alter brain activation in brain regions monitoring voice identity and unexpected changes in voice playback quality. FMRI results confirmed a self‐voice suppression effect in the right anterior superior temporal gyrus (aSTG) when self‐voice attribution was unambiguous. Although the right inferior frontal gyrus (IFG) was more active during a self‐generated compared to a passively‐heard voice, the putative role of this region in detecting unexpected self‐voice changes during action was demonstrated only when hearing the voice of another speaker and not when attribution was uncertain. Further research on the link between right aSTG and IFG is required and may establish a threshold monitoring voice identity in action. The current results have implications for a better understanding of the altered experience of self‐voice feedback in auditory verbal hallucinations

Prospectively Collected Characteristics of Adult Patients, Their Consultations and Outcomes as They Report Breathlessness When Presenting to General Practice in Australia

Introduction:Breathlessness is a subjective sensation, so understanding its impacts requires patients' reports, including prospective patient-defined breathlessness as a reason for presenting to general practitioners (GP).The aim of this study was to define the prevalence of breathlessness as a reason for GP consultations while defining the clinico-demographic factors of these patients and the characteristics and outcomes of those consultations.Methods:Using nine years of the Family Medicine Research Centre database of 100 consecutive encounters from 1,000 practices annually, the patient-defined reason for encounter 'breathlessness' was explored using prospectively collected data in people ≥18 years with clinical data coded using the International Classification for Primary Care V2. Dichotomous variables were analysed using chi square and 95% confidence intervals calculated using Kish's formula for a single stage clustered design.Results:Of all the 755,729 consultations collected over a nine year period from 1 April, 2000, 7255 included breathlessness as a reason for encounter (0.96%; 95% CI 0.93 to 0.99) most frequently attributed to chronic obstructive pulmonary disease. Only 48.3% of GPs saw someone reporting breathlessness. The proportion of consultations with breathlessness increased with age. Breathlessness trebled the likelihood that the consultation occurred in the community rather than the consulting room (p<0.0001) and increased 2.5 fold the likelihood of urgent referral to hospital (p<0.0001). Of those with breathlessness, 12% had undiagnosed breathlessness at the end of the consultation (873/7255) with higher likelihood of being younger females.Discussion:Breathlessness is a prevalent symptom in general practitioner. Such prevalence enables future research focused on understanding the temporal pattern of breathlessness and the longitudinal care offered to, and outcomes for these patients, including those who leave the consultation without a diagnosis. © 2013 Currow et al

Measuring distance through dense weighted networks: The case of hospital-associated pathogens

Hospital networks, formed by patients visiting multiple hospitals, affect the spread of hospital-associated infections, resulting in differences in risks for hospitals depending on their network position. These networks are increasingly used to inform strategies to prevent and control the spread of hospital-associated pathogens. However, many studies only consider patients that are received directly from the initial hospital, without considering the effect of indirect trajectories through the network. We determine the optimal way to measure the distance between hospitals within the network, by reconstructing the English hospital network based on shared patients in 2014–2015, and simulating the spread of a hospital-associated pathogen between hospitals, taking into consideration that each intermediate hospital conveys a delay in the further spread of the pathogen. While the risk of transferring a hospital-associated pathogen between directly neighbouring hospitals is a direct reflection of the number of shared patients, the distance between two hospitals far-away in the network is determined largely by the number of intermediate hospitals in the network. Because the network is dense, most long distance transmission chains in fact involve only few intermediate steps, spreading along the many weak links. The dense connectivity of hospital networks, together with a strong regional structure, causes hospital-associated pathogens to spread from the initial outbreak in a two-step process: first, the directly surrounding hospitals are affected through the strong connections, second all other hospitals receive introductions through the multitude of weaker links. Although the strong connections matter for local spread, weak links in the network can offer ideal routes for hospital-associated pathogens to travel further faster. This hold important implications for infection prevention and control efforts: if a local outbreak is not controlled in time, colonised patients will appear in other regions, irrespective of the distance to the initial outbreak, making import screening ever more difficult

An assessment of potential unintended consequences following a national antimicrobial stewardship programme in England: an interrupted time series analysis

Background: The 'Quality Premium' (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. Methods: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of pre-defined conditions of unintended consequences of reduced prescribing. Monthly age and sex-standardised rates were calculated using a direct method of standardisation. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. Results: We identified 27,334 GP consultations and over five million emergency hospital admissions with pre-defined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. Conclusions: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers

Chewing gum benefits sustained attention in the absence of task degradation.

OBJECTIVES: The present study examined the effect of chewing gum on sustained attention and associated changes in subjective alertness. METHODS: In a within-participants design, 20 participants completed an extended version of the sustained attention response task (SART: Robertson et al., 1997), both with and without chewing gum. Self-rated measures of alertness, contentedness, and calmness were taken before and after the SART. RESULTS: Chewing gum was associated with improved attentional task performance. This finding was not contingent upon a general decrease in attentional performance and was apparent at all stages of the task. Subjective measures of alertness, contentedness, and calmness were higher following the chewing of gum. Changes in sustained attention co-varied with subjective alertness. DISCUSSION: The effects of chewing gum on attention and alertness are consistent with past literature and were not contingent on declines in attention. Additionally, we found evidence that gum-induced changes in self-rated alertness and attention are related. We found no support for the proposition that chewing gum can impair attention due to the division of resources

Using a Multi-Level Process Comparison for Process Change Analysis in Cancer Pathways

The area of process change over time is a particular concern in healthcare, where patterns of care emerge and evolve in response to individual patient needs. We propose a structured approach to analyse process change over time that is suitable for the complex domain of healthcare. Our approach applies a qualitative process comparison at three levels of abstraction: a holistic perspective (process model), a middle-level perspective (trace), and a fine-grained detail (activity). Our aim was to detect change points, localise and characterise the change, and unravel/understand the process evolution. We illustrate the approach using a case study of cancer pathways in Leeds where we found evidence of change points identified at multiple levels. In this paper, we extend our study by analysing the miners used in process discovery and providing a deeper analysis of the activity of investigation in trace and activity levels. In the experiment, we show that this qualitative approach provides a useful understanding of process change over time. Examining change at three levels provides confirmatory evidence of process change where perspectives agree, while contradictory evidence can lead to focused discussions with domain experts. This approach should be of interest to others dealing with processes that undergo complex change over time

Descriptive epidemiology of Escherichia coli bacteraemia in England, April 2012 to March 2014

We determined the incidence, risk factors and antimicrobial susceptibility associated with Escherichia coli bacteraemia in England over a 24 month period. Case data were obtained from the national mandatory surveillance database, with susceptibility data linked from LabBase2, a voluntary national microbiology database. Between April 2012 and March 2014, 66,512 E. coli bacteraemia cases were reported. Disease incidence increased by 6% from 60.4 per 100,000 population in 2012-13 to 63.5 per 100,000 population in 2013-14 (p < 0.0001). Rates of E. coli bacteraemia varied with patient age and sex, with 70.5% (46,883/66,512) of cases seen in patients aged ≥ 65 years and 52.4% (33,969/64,846) of cases in females. The most common underlying cause of bacteraemia was infection of the genital/urinary tract (41.1%; 27,328/66,512), of which 98.4% (26,891/27,328) were urinary tract infections (UTIs). The majority of cases (76.1%; 50,617/66,512) had positive blood cultures before or within two days of admission and were classified as community onset cases, however 15.7% (10,468/66,512) occurred in patients who had been hospitalised for over a week. Non-susceptibility to ciprofloxacin, third-generation cephalosporins, piperacillin-tazobactam, gentamicin and carbapenems were 18.4% (8,439/45,829), 10.4% (4,256/40,734), 10.2% (4,694/46,186), 9.7% (4,770/49,114) and 0.2% (91/42,986), respectively. Antibiotic non-susceptibility was higher in hospital-onset cases than for those presenting from the community (e.g. ciprofloxacin non-susceptibility was 22.1% (2,234/10,105) for hospital-onset vs 17.4% (5,920/34,069) for community-onset cases). Interventions to reduce the incidence of E. coli bacteraemia will have to target the community setting and UTIs if substantial reductions are to be realised