Cryptococcal infections over a 15 year period at a tertiary facility & impact of guideline management

Introduction: The aim of this research paper is to determine the incidence, risk factors and clinical outcome of all patients diagnosed and treated for cryptococcosis at our institution. We also aim to compare treatment outcome following introduction of the 2010 Infectious Disease Society of America (IDSA) guidelines. Methods: Retrospective analysis of all patients diagnosed and treated for cryptococcal infection occurring between January 2001 and December 2015. Results: Of 102 patients diagnosed with cryptococcal infection, 97 were eligible for study inclusion. There appears to be an overall increased incidence of cryptococcosis in both transplant and non-transplant cohorts with a peak in 2015 of 6 transplant and 13 non-transplant cases. 38/52 (73%) of identified isolates were C. neoformans, and 14/52 (27%) were C. gattii. Notably, 14/14 (100%) of C. gattii isolates were associated with meningitis, as compared to only 38/64 (59%) C. neoformans associated with meningitis (p: 0.003). It appears that patients presenting with cough are less likely to have meningitis, 17/27 (63%), (p: 0.005). When stratifying for culture positive meningitis lumbar puncture opening pressure, the median in the culture positive cohort was 31.5cmH2 O compared with 15.5cmH2O (p:0.036). Multiple admissions were required prior to diagnosis in the majority of cases with only 18/72 (25%) diagnosed on 1st presentation. Post-guideline mortality has improved from 17.1% to 6.1% (p: 0.046). Conclusion: Cryptococcal infection remains relatively uncommon, but there appears to be an increasing trend in incidence. Overall mortality is relatively low and has improved since introduction of the 2010 IDSA guidelines

The Role of Cognitive Factors in Predicting Balance and Fall Risk in a Neuro-Rehabilitation Setting

INTRODUCTION: There is a consistent body of evidence supporting the role of cognitive functions, particularly executive function, in the elderly and in neurological conditions which become more frequent with ageing. The aim of our study was to assess the role of different domains of cognitive functions to predict balance and fall risk in a sample of adults with various neurological conditions in a rehabilitation setting. METHODS: This was a prospective, cohort study conducted in a single centre in the UK. 114 participants consecutively admitted to a Neuro-Rehabilitation Unit were prospectively assessed for fall accidents. Baseline assessment included a measure of balance (Berg Balance Scale) and a battery of standard cognitive tests measuring executive function, speed of information processing, verbal and visual memory, visual perception and intellectual function. The outcomes of interest were the risk of becoming a faller, balance and fall rate. RESULTS: Two tests of executive function were significantly associated with fall risk, the Stroop Colour Word Test (IRR 1.01, 95% CI 1.00-1.03) and the number of errors on part B of the Trail Making Test (IRR 1.23, 95% CI 1.03-1.49). Composite scores of executive function, speed of information processing and visual memory domains resulted in 2 to 3 times increased likelihood of having better balance (OR 2.74 95% CI 1.08 to 6.94, OR 2.72 95% CI 1.16 to 6.36 and OR 2.44 95% CI 1.11 to 5.35 respectively). CONCLUSIONS: Our results show that specific subcomponents of executive functions are able to predict fall risk, while a more global cognitive dysfunction is associated with poorer balance

Focal Adhesion Kinase regulates cell–cell contact formation in epithelial cells via modulation of Rho

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase that plays a key role in cellular processes such as cell adhesion, migration, proliferation and survival. Recent studies have also implicated FAK in the regulation of cell-cell adhesion. Here, evidence is presented showing that siRNA-mediated suppression of FAK levels in NBT-II cells and expression of dominant negative mutants of FAK caused loss of epithelial cell morphology and inhibited the formation of cell-cell adhesions. Rac and Rho have been implicated in the regulation of cell-cell adhesions and can be regulated by FAK signaling. Expression of active Rac or Rho in NBT-II cells disrupted formation of cell-cell contacts, thus promoting a phenotype similar to FAK-depleted cells. The loss of intercellular contacts in FAK-depleted cells is prevented upon expression of a dominant negative Rho mutant, but not a dominant negative Rac mutant. Inhibition of FAK decreased tyrosine phosphorylation of p190RhoGAP and elevated the level of GTP-bound Rho. This suggests that FAK regulates cell-cell contact formation by regulation of Rho

Health Outcome after Major Trauma: What Are We Measuring?

Importance: Trauma is a global disease and is among the leading causes of disability in the world. The importance of outcome beyond trauma survival has been recognised over the last decade. Despite this there is no internationally agreed approach for assessment of health outcome and rehabilitation of trauma patients. Objective: To systematically examine to what extent outcomes measures evaluate health outcomes in patients with major trauma. Data sources: MEDLINE, EMBASE, and CINAHL (from 2006-2012) were searched for studies evaluating health outcome after traumatic injuries. STUDY SELECTION AND DATA EXTRACTION: Studies of adult patients with injuries involving at least two body areas or organ systems were included. Information on study design, outcome measures used, sample size and outcomes were extracted. The World Health Organisation International Classification of Function, Disability and Health (ICF) were used to evaluate to what extent outcome measures captured health impacts. Results: 34 studies from 755 studies were included in the review. 38 outcome measures were identified. 21 outcome measures were used only once and only five were used in three or more studies. Only 6% of all possible health impacts were captured. Concepts related to activity and participation were the most represented but still only captured 12% of all possible concepts in this domain. Measures performed very poorly in capturing concepts related to body function (5%), functional activities (11%) and environmental factors (2%). Conclusion: Outcome measures used in major trauma capture only a small proportion of health impacts. There is no inclusive classification for measuring disability or health outcome following trauma. The ICF may provide a useful framework for the development of a comprehensive health outcome measure for trauma care

Telerehabilitation for people with physical disabilities and movement impairment: development and evaluation of an online toolkit for practitioners and patients.

PURPOSE: Telerehabilitation has increasingly been used since the COVID-19 pandemic but with limited guidance available on undertaking physical assessments using remote methods. We aimed to provide such guidance by developing a Telerehab Toolkit, an online information and training resource for practitioners, patients, and carers on telerehabilitation for people with physical disabilities and movement impairment. MATERIALS AND METHODS: Development and evaluation of the toolkit were informed by the Knowledge to Action framework and took place iteratively in two phases-knowledge creation and action. Information was collated from various sources including literature review, online survey, service evaluation, and focus group discussions. The toolkit has been evaluated using think-aloud interviews, e-mail and social media feedback from users, and analytics data on user engagement with the website. RESULTS: The Telerehab Toolkit focuses on remote physical assessments, and contains information on technology, digital skills, remote assessment tools, information governance, and safety for telerehabilitation. Resources include top tips from practitioners and patients, how-to guides, checklists, videos, and links to evidence. CONCLUSIONS: The Telerehab Toolkit has been well-received by practitioners, healthcare students, patients, and carers, is being disseminated widely, and is freely available (www.plymouth.ac.uk/research/telerehab). IMPLICATIONS FOR REHABILITATIONTelerehabilitation has been increasingly used since the COVID-19 pandemic, but with limited guidance and training for practitioners on undertaking safe and effective remote physical assessments.The Telerehab Toolkit has been developed iteratively using the Knowledge to Action framework; it is a free online resource for practitioners and patients with specific guidance on telerehabilitation for physical disabilities and movement impairment.It is anticipated that the resource will help to improve the knowledge, skills, and confidence of the current and future rehabilitation workforce

Measures Matter: Scales for Adaptation, Cultural Distance, and Acculturation Orientation Revisited

Building upon existing measures, four new brief acculturation scales are presented, measuring sociocultural adaptation, psychological adaptation, perceived cultural distance, and acculturation orientation. Following good scale reliability in initial samples, the English scales were translated into nine different languages (Chinese, French, German, Italian, Japanese, Portuguese, Spanish, Thai, and Turkish). The translated scales were administered to a large sample of sojourners (N = 1,929), demonstrating good reliability and adequate structural equivalence across languages. In line with existing theory, sociocultural adaptation and psychological adaptation were positively correlated, and showed a negative association with perceived cultural distance. General measures of well-being were correlated with adaptation and distance, with better adaptation relating to higher well-being, and more distance relating to lower well-being. Acculturation orientation toward the home and host culture were measured separately and a weak negative correlation was found between the two, supporting their independence. Arguing against dichotomization, these subscales were analyzed as continuous variables. Regression analysis showed sojourners to be better adapted, if they were oriented more toward the host culture and less toward the home culture. These new scales are proposed as alternatives to existing measures

Identification of a Filamin Docking Site on PTP-PEST

PTP-PEST is a cytoplasmic protein-tyrosine phosphatase (PTP) implicated in the regulation of biological processes such as cell motility, cytokinesis, focal adhesion disassembly, and lymphocyte activation. Using a proteomics approach, filamin-A was identified as a novel interacting protein that bound to GST-PTP-PEST. This interaction was confirmed in vitro and in cells by coimmunoprecipitation. The site of filamin interaction on PTP-PEST was mapped to the fourth proline-rich region (Pro4). PTP-PEST has previously been implicated in the regulation of cytokinesis. In further support of this finding, expression of PTP-PEST in HeLa cells resulted in the formation of multinucleated cells. A PTP-PEST mutant lacking Pro4 and unable to bind filamin-A failed to induce the multinucleated phenotype. Further, depletion of filamin-A in HeLa cells was found to reduce the PTP-PEST-dependent multinucleation phenotype. Hence, we conclude that the interaction of PTP-PEST with filamin-A may function in the control of cytokinesis in mammalian cells

Late recovery of awareness in prolonged disorders of consciousness -a cross-sectional cohort study

PURPOSE: To detect any improvement of awareness in prolonged disorders of consciousness in the long term. METHODS: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21-73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2-16 years later using Coma Recovery Scale-Revised. RESULTS: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean = 45, SD = 11.4) and non-recovery group (Mean = 43, SD = 15.5) were not statistically different (p = 0.76). CONCLUSIONS: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered. Implications for rehabilitation Long-term regular follow-up of people with prolonged disorders of consciousness is important. Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases. Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered

Prevalence and outcomes of low‐gradient severe aortic stenosis—from the National Echo Database of Australia

Background: The prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results: Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS. Conclusions: Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS

Intestinal fatty-acid binding protein and gut permeability responses to exercise

Purpose Intestinal cell damage due to physiological stressors (e.g. heat, oxidative, hypoperfusion/ischaemic) may contribute to increased intestinal permeability. The aim of this study was to assess changes in plasma intestinal fatty acid-binding protein (I-FABP) in response to exercise (with bovine colostrum supplementation, Col, positive control) and compare this to intestinal barrier integrity/permeability (5 h urinary lactulose/rhamnose ratio, L/R). Methods In a double-blind, placebo-controlled, crossover design, 18 males completed two experimental arms (14 days of 20 g/day supplementation with Col or placebo, Plac). For each arm participants performed two baseline (resting) intestinal permeability assessments (L/R) pre-supplementation and one post-exercise following supplementation. Blood samples were collected pre- and post-exercise to determine I-FABP concentration. Results Two-way repeated measures ANOVA revealed an arm?×?time interaction for L/R and I-FABP (P?<?0.001). Post hoc analyses showed urinary L/R increased post-exercise in Plac (273% of pre, P?<?0.001) and Col (148% of pre, P?<?0.001) with post-exercise values significantly lower with Col (P?<?0.001). Plasma I-FABP increased post-exercise in Plac (191% of pre-exercise, P?=?0.002) but not in the Col arm (107%, P?=?0.862) with post-exercise values significantly lower with Col (P?=?0.013). Correlations between the increase in I-FABP and L/R were evident for visit one (P?=?0.044) but not visit two (P?=?0.200) although overall plots/patterns do appear similar for each. Conclusion These findings suggest that exercise-induced intestinal cellular damage/injury is partly implicated in changes in permeability but other factors must also contribute