Neurological rehabilitation following heat illness in the UK Armed Forces.

Heat illness remains a significant threat to health in the UK Armed Forces despite recent improvements in the prevention of cases. A small number of heat illness survivors develop long-term neurological sequelae. Here we briefly review the background literature and present our experience of treating UK Armed Forces patients with neurological consequences of heat illness. In our cohort of patients, we observed significant improvements in subjective symptoms and objective assessments following a period of neurological rehabilitation at the Defence Medical Rehabilitation Centre. We conclude with recommendations for further research and for the incorporation of screening for neurological disability following heat illness into service policy.

Review of neurological rehabilitation for Multiple Sclerosis in the British Military.

Multiple sclerosis (MS) is a progressive neurological disorder, classically presenting in working age adults, including those in the Armed Forces. The Defence Medical Rehabilitation Centre (DMRC) Stanford Hall offers vocationally focused neurorehabilitation services for service personnel (SP) with MS, with the goal to minimise disability, maximise independence and remain able to work.This paper has two aims. First, it briefly provides a clinical update of MS, focusing on pathology, presentation, diagnosis and management. Finally, it will describe the role of DMRC and data from the last decade in the management of MS.Our findings suggest not all SP with MS are being referred to DMRC, and some of those who do have significant delays, potentially impacting on patient support, symptom management and occupational outcomes. It is hoped that this paper will improve awareness and recognition of MS for Armed Forces personnel.

Unexpected difficult tracheal intubation secondary to subglottic stenosis leading to emergency front-of-neck airway.

A 26-year-old woman presenting for an elective day case procedure under general anaesthesia had undiagnosed subglottic stenosis leading to a life threatening airway emergency requiring emergency front-of-neck airway. We outline the case and discuss key anaesthetic considerations in subglottic stenosis, including concerning features of a medical/anaesthetic history and the potential for rapid deterioration of a stenotic airway following manipulation. We also consider the effect of anaesthesia on the calibre of subglottic stenosis and the effects of positive pressure ventilation. Subglottic stenosis is a rare condition with congenital, acquired and idiopathic origins; however, iatrogenic trauma is the most common cause. We are aware of a small number of published case reports of previously undiagnosed subglottic stenosis in adults discovered after induction of anaesthesia; situational deterioration to 'cannot intubate, cannot oxygenate' scenarios appear even rarer.

Knowledge, Attitudes and Practices of Drivers towards Road Traffic Regulations in Trinidad, West Indies

This study aims to test the knowledge, practices & attitudes of drivers in Trinidad through issuing a questionnaire based on driving practices in relation to seat belt use, alcohol consumption, fatigue & distraction, and a quiz, which focuses on road regulations. The information obtained from this study can be used to prevent accidents by identifying: poor knowledge, driving practices and attitudes in the driving population of Trinidad.

Is Blastomycosis Endemic in Upstate New York?: A Case Report and Review of Literature.

CASE: We describe a case of biopsy-proven blastomycosis in a patient residing in Upstate New York with osseous and skin lesions and no pulmonary or constitutional symptoms. The patient had a rapid resolution of symptoms after the initiation of antifungal treatment, followed by curettage and cementation of her distal femoral lesion. CONCLUSIONS: Orthopaedic surgeons should be aware of the presence of blastomycosis in nonendemic areas, especially since bone involvement may be the predominant manifestation. Tissue should be submitted for both histologic and microbiologic analysis. Antifungal therapy and surgical management if needed can result in a good outcome.

An electronic patient-reported outcomes measurement system in paediatric orthopaedics.

PURPOSE: The purpose of the study was to evaluate the reliability, review differences and assess patient satisfaction of electronic patient-reported outcome measures (PROMs) compared with paper PROMs. METHODS: Participants between 12 and 19 years of age with a knee-related primary complaint were randomized into two groups. Group 1 completed paper PROMs followed by electronic, while Group 2 received the electronic followed by paper. PROMs included the Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery (HSS) Pediatric Functional Activity Brief Scale (HSS Pedi-FABS), Tegner Activity Level Scale, Visual Analogue Scale (VAS), PedsQL Teen and a satisfaction survey. RESULTS: In all, 87 participants were enrolled with one excluded due to incomplete PROMs. Of the 86 participants, 54 were female and 32 were male with an average age of 14.3 years (12 to 18). A high degree of reliability was found when comparing the paper and electronic versions of the Pedi-IKDC (0.946; p < 0.001), HSS Pedi-FABS (0.923; p < 0.001), PedsQL Teen (0.894; p < 0.001), Tegner Activity Level Scale before injury (0.848; p < 0.001) and the Tegner Activity Level Scale after (0.930; p < 0.001). Differences were noted between the VAS scores, with paper scores being significantly higher than electronic (5.3 versus 4.6; p < 0.001). While not significant, a trend was noted in which electronic PROMs took, overall, less time than paper (10.0 mins versus 11.2 mins; p = 0.096).Of all participants, 69.8% preferred the electronic PROMs, 67.4% felt they were faster, 93.0% stated they would complete forms at home prior to appointments and 91.8% were not concerned about the safety/privacy of electronic forms. CONCLUSION: PROMs captured electronically were reliable when compared with paper. Electronic PROMs may be quicker, will not require manual scoring and are preferred by patients. LEVEL OF EVIDENCE: II.

Influenza and vaccination: beliefs and practices of local authority staff.

BACKGROUND: Influenza causes large outbreaks every year. Professionals outside healthcare, including social care staff and non-care giving roles, have a key role in protecting their clients and sustaining operational productivity through influenza vaccination. There has been little research on non-healthcare staff working with vulnerable people and those working in non-caregiving settings regarding influenza and influenza vaccination. AIMS: To understand the practices, experiences, perceptions and motivations of local authority staff regarding influenza and influenza vaccination. METHODS: Semi-structured focus groups were carried out with local authority staff in Gloucestershire. Transcripts were thematically analysed. RESULTS: Participants tended to perceive influenza as a serious illness, where a person had a specific risk factor or during pandemics. They did not feel vulnerable unless they had previous experience of infection or had an underlying health condition. Motivation to vaccinate was based on previous experience of influenza, where they had a close family member at risk or when working directly with vulnerable clients. Beliefs about negative side effects of the vaccine were the strongest reason for vaccine refusal. Ease of access to vaccination through on-site clinics is key to uptake. Management are perceived as key motivators or blockers to vaccine uptake. CONCLUSIONS: Workers outside healthcare settings do not feel vulnerable to influenza and have low motivation to vaccinate, unless they have previous experience of infection or an underlying health condition. Vaccination programmes must proactively address workers' beliefs and motivations to ensure their participation in flu vaccination programmes.

MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis.

OBJECTIVES: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable ß-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 µM·h) in >80% of the intended population. METHODS: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. RESULTS: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. CONCLUSIONS: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.

Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches.

Glioblastoma is the most common primary adult brain tumour, and despite optimal treatment, the median survival is 12-15 months. Patients with matched recurrent glioblastomas were investigated to try to find actionable mutations. Tumours were profiled using a validated DNA-based gene panel. Copy number variations (CNVs) and single nucleotide variants (SNVs) were examined, and potentially pathogenic variants and clinically actionable mutations were identified. The results revealed that glioblastomas were IDH-wildtype (IDH WT; n = 38) and IDH-mutant (IDH MUT; n = 3). SNVs in TSC2, MSH6, TP53, CREBBP, and IDH1 were variants of unknown significance (VUS) that were predicted to be pathogenic in both subtypes. IDH WT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein pathways. Many tumours had BRCA1/2 (18%) variants, including confirmed somatic mutations in haemangioblastoma. IDH WT recurrent tumours had fewer pathways impacted (RTK/Ras/PI(3)K, p53, WNT, and G-protein) and CNV gains (BRCA2, GNAS, and EGFR) and losses (TERT and SMARCA4). IDH MUT tumours had SNVs that impacted RTK/Ras/PI(3)K, p53, and WNT pathways. VUS in KLK1 was possibly pathogenic in IDH MUT. Recurrent tumours also had fewer pathways (p53, WNT, and G-protein) impacted by genetic alterations. Public datasets (TCGA and GDC) confirmed the clinical significance of findings in both subtypes. Overall in this cohort, potentially actionable variation was most often identified in EGFR, PTEN, BRCA1/2, and ATM. This study underlines the need for detailed molecular profiling to identify individual GBM patients who may be eligible for novel treatment approaches. This information is also crucial for patient recruitment to clinical trials.

Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir.

PURPOSE: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN). METHODS: Retrospective chart review. RESULTS: Four immunocompetent men aged 45-90 years presented with ARN from 2008-2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2-8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40). CONCLUSIONS: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.

Accuracy of giant African pouched rats for diagnosing tuberculosis: comparison with culture and Xpert® MTB/RIF.

SETTING: Enhanced tuberculosis (TB) case finding using detection rats in Tanzania. OBJECTIVES: To assess the diagnostic accuracy of detection rats compared with culture and Xpert® MTB/RIF, and to compare enhanced case-finding algorithms using rats in smear-negative presumptive TB patients. DESIGN: A fully paired diagnostic accuracy study in which sputum of new adult presumptive TB patients in Tanzania was tested using smear microscopy, 11 detection rats, culture and Xpert. RESULTS: Of 771 eligible participants, 345 (45%) were culture-positive for Mycobacterium tuberculosis, and 264 (34%) were human immunodeficiency virus (HIV) positive. The sensitivity of the detection rats was up to 75.1% (95%CI 70.1-79.5) when compared with culture, and up to 81.8% (95%CI 76.0-86.5) when compared with Xpert, which was statistically significantly higher than the sensitivity of smear microscopy. Corresponding specificity was 40.6% (95%CI 35.9-45.5) compared with culture. The accuracy of rat detection was independent of HIV status. Using rats for triage, followed by Xpert, would result in a statistically higher yield than rats followed by light-emitting diode fluorescence microscopy, whereas the number of false-positives would be significantly lower than when using Xpert alone. CONCLUSION: Although detection rats did not meet the accuracy criteria as standalone diagnostic or triage testing for presumptive TB, they have additive value as a triage test for enhanced case finding among smear-negative TB patients if more advanced diagnostics are not available.

Identification of coeliac disease triggering glutenin peptides in adults.

OBJECTIVE: Coeliac disease affects approximately 1% of Northern American and European populations. It is caused by an inappropriate immune response to dietary gluten. Gluten comprises of two major protein fractions: gliadins and glutenins. Glutenins have recently been found to be toxic to coeliac individuals. Proliferation assays suggest in some but not all paediatric coeliac individuals there may be immunological stimulation with high molecular weight (HMW) glutenins. Less evidence pertains to low molecular weight (LMW) glutenins. The aim is to assess adaptive, T-cell driven, and innate immune response in adult coeliac individuals towards HMW glutenin peptide, glut04, and LMW glutenin peptide, glt156. MATERIALS AND METHODS: Coeliac patients were recruited attending endoscopy for routine monitoring. Adaptive immune response towards glut04 and glt156 was measured by proliferation assays and measurement of interferon-γ secretion in 28 T-cell lines. The innate immune response was assessed by measurement of enterocyte cell height (ECH) in coeliac small intestinal biopsies following overnight incubation in organ culture chambers in a further nine individuals. RESULTS: There were 3/28 and 2/28 positive proliferation results using gluten-sensitive T-cells with glut04 and glt156, respectively. All coeliac biopsies tested in organ culture chambers demonstrated clear reduction in ECH with peptic-tryptic digest of whole industrial gluten, glut04 and glt156 when compared to negative control ovalbumin (p < 0.005). Three individuals had both T-cell and organ culture study data. Their proliferation assays showed no stimulation of the T-cells. CONCLUSIONS: This study demonstrates glutenin epitopes glut04 and glt156, while minor T-cell epitopes, are important in their ability to trigger the innate immune response.

Sleep disturbances are associated with reduced health-related quality of life in patients with substance use disorders.

BACKGROUND AND OBJECTIVES: Sleep problems and substance use are strongly linked. Sleep problems play a role in the etiology of substance use, but also may be a result of it. After detoxification, sleep problems may worsen leading to relapse. Nowadays, most substance dependence treatment programs aim at recovery rather than total abstinence, and in that view health-related quality of life (HRQL) is a relevant construct. This article describes the association between self-perceived sleep problems and HRQL in a naturalistic population of polydrug-using inpatients. METHODS: At the start of treatment, 388 polydrug-using inpatients completed questionnaires concerning their sleep quality and HRQL. Three categories were established based on reported sleep problems: patients without sleep problems (21.6%), those with clinically relevant sleep problems (34.5%), and patients with sleep disorders (43.8%). RESULTS: Mean grades for quality of sleep were M = 7.3 (sd 1.7), M = 6.6 (sd 1.7) and M = 5.3 (sd 1.9) for the three categories, respectively. In addition, patients in the disorder category perceived a lower HRQL than those in the other categories. In the explanation of HRQL, both sleep problems and sleep disorders added significantly to the model when controlling for baseline characteristics. DISCUSSION AND CONCLUSIONS: Our findings stress the need for clinicians to pay attention to the quality of sleep of recovering polydrug users, since this may play an important role in the recovery process. Monitoring sleep during treatment is advocated. This study adds to the knowledge about the way HRQL and sleep are related in a naturalistic sample of substance-dependent patients.

An organic hydrophilic dye for water-based dye-sensitized solar cells.

In this study we report the first organic hydrophilic dye employed for 100% water-based electrolyte DSSCs. We show that the replacement of alkyl by glycolic chains in the dye structure is able to provide excellent wettability, resulting in an efficient system with remarkably reduced desorption problems that allowed us to perform tests over a wide pH range. By changing the electrolyte composition, employing chenodeoxycholic acid as a co-adsorbent and using PEDOT counter-electrodes, 3% power conversion efficiency under 1-sun illumination was obtained. We show that chenodeoxycholic acid does not significantly increase the wettability, and we provide new insights into the higher performance resulting from its co-adsorption.

Gastrointestinal effects of eating quinoa (Chenopodium quinoa Willd.) in celiac patients.

OBJECTIVES: Celiac disease is an enteropathy triggered by dietary gluten found in wheat, rye, and barley. Treatment involves a strict gluten-free diet (GFD). Quinoa is a highly nutritive plant from the Andes that has been recommended as part of a GFD. However, in-vitro data suggested that quinoa prolamins can stimulate innate and adaptive immune responses in celiac patients. Therefore, we aimed to evaluate the in-vivo effects of eating quinoa in adult celiac patients. METHODS: Nineteen treated celiac patients consumed 50 g of quinoa every day for 6 weeks as part of their usual GFD. We evaluated diet, serology, and gastrointestinal parameters. Furthermore, we carried out detail histological assessment of 10 patients before and after eating quinoa. RESULTS: Gastrointestinal parameters were normal. The ratio of villus height to crypt depth improved from slightly below normal values (2.8:1) to normal levels (3:1), surface-enterocyte cell height improved from 28.76 to 29.77 µm and the number of intra-epithelial lymphocytes per 100 enterocytes decreased from 30.3 to 29.7. Median values for all the blood tests remained within normal ranges, although total cholesterol (n=19) decreased from 4.6 to 4.3 mmol/l, low-density lipoprotein decreased from 2.46 to 2.45 mmol/l, high-density lipoprotein decreased from 1.8 to 1.68 mmol/l and triglycerides decreased from 0.80 to 0.79 mmol/l. CONCLUSIONS: Addition of quinoa to the GFD of celiac patients was well tolerated and did not exacerbate the condition. There was a positive trend toward improved histological and serological parameters, particularly a mild hypocholesterolemic effect. Overall, this is the first clinical data suggesting that daily 50 g of quinoa for 6 weeks can be safely tolerated by celiac patients. However, further studies are needed to determine the long-term effects of quinoa consumption.

The “Angle of Louis”

The 'angle of Louis' is a well-known anatomical landmark. Formed by the junction between the manubrium and sternal body, it marks the level of the 2nd rib and defines the boundary between the superior and inferior mediastinum. Despite our familiarity with this angle, there remains confusion over the eponym. This is reflected by the variations of the name in the literature - Louis, Ludovici, Ludovicus, Ludwick and Ludwig - and the different people it has been attributed to. Sources have referenced the French clinician Antoine Louis, the French surgeon Alexandre Louis and the German physician Wilhelm Friedrich von Ludwig. Interestingly on investigating these potential candidates we found no formal description of the sternal angle in their writings. Pierre Alexandre comes closest however, when he describes a ‘prominence’ in the upper part of the chest which he relates to severe emphysema. We propose that the sternal angle was named in honour of Pierre Alexandre, although he did not himself characterise it as an anatomical landmark (AU)

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Evaluation of the safety of ancient strains of wheat in coeliac disease reveals heterogeneous small intestinal T cell responses suggestive of coeliac toxicity.

BACKGROUND & AIMS: Coeliac disease is a chronic small intestinal immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals. Since it is unknown if all wheat varieties are equally toxic to coeliac patients seven Triticum accessions showing different origin (ancient/modern) and ploidy (di-, tetra- hexaploid) were studied. MATERIALS AND METHODS: Selected strains of wheat were ancient Triticum monococcum precoce (AA genome) and Triticum speltoides (BB genome), accessions of Triticum turgidum durum (AABB genome) including two ancient (Graziella Ra and Kamut) and two modern (Senatore Cappelli and Svevo) durum strains of wheat and Triticum aestivum compactum (AABBDD genome). Small intestinal gluten-specific T-cell lines generated from 13 coeliac patients were tested with wheat accessions by proliferation assays. RESULTS: All strains of wheat independent of ploidy or ancient/modern origin triggered heterogeneous responses covering wide ranges of stimulation indices. CONCLUSION: Ancient strains of wheat, although previously suggested to be low or devoid of coeliac toxicity, should be tested for immunogenicity using gluten-specific T-cell lines from multiple coeliac patients rather than gluten-specific clones to assess their potential toxicity. Our findings provide further evidence for the need for a strict gluten-free diet in coeliac patients, including avoidance of ancient strains of wheat.