Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice.

Secure and Scalable Statistical Computation of Questionnaire Data in R

Collecting data via a questionnaire and analyzing them while preserving respondents’ privacy may increase the number of respondents and the truthfulness of their responses. It may also reduce the systematic differences between respondents and non-respondents. In this paper, we propose a privacy-preserving method for collecting and analyzing survey responses using secure multi-party computation (SMC). The method is secure under the semi-honest adversarial model. The proposed method computes a wide variety of statistics. Total and stratified statistical counts are computed using the secure protocols developed in this paper. Then, additional statistics, such as a contingency table, a chi-square test, an odds ratio, and logistic regression, are computed within the R statistical environment using the statistical counts as building blocks. The method was evaluated on a questionnaire dataset of 3,158 respondents sampled for a medical study and simulated questionnaire datasets of up to 50,000 respondents. The computation time for the statistical analyses linearly scales as the number of respondents increases. The results show that the method is efficient and scalable for practical use. It can also be used for other applications in which categorical data are collected.

Towards a Virtual-Acoustic String Instrument

In acoustic instruments, the controller and the sound producing system often are one and the same object. If virtualacoustic instruments are to be designed to not only simulate the vibrational behaviour of a real-world counterpart but also to inherit much of its interface dynamics, it would make sense that the physical form of the controller is similar to that of the emulated instrument. The specific physical model configuration discussed here reconnects a (silent) string controller with a modal synthesis string resonator across the real and virtual domains by direct routing of excitation signals and model parameters. The excitation signals are estimated in their original force-like form via careful calibration of the sensor, making use of adaptive filtering techniques to design an appropriate inverse filter. In addition, the excitation position is estimated from sensors mounted under the legs of the bridges on either end of the prototype string controller. The proposed methodology is explained and exemplified with preliminary results obtained with a number of off-line experiments.

Vaisseau sanguin reconstruit par génie tissulaire : Développement d'une nouvelle approche pour la reconstruction de la media et interaction avec les microparticules

La media vasculaire est au coeur des processus physiopathologiques qui entraînent le développement de l’athérosclérose. L’utilisation d’une media reconstruite par génie tissulaire permet d’étudier les cellules musculaires lisses (CML) humaines dans un environnement plus physiologique que les cellules en culture monocouche. Les travaux présentés dans cette thèse sont orientés autour de la media vasculaire reconstruite par génie tissulaire comme modèle d’étude pharmacologique et prothèse vasculaire autologue. La première partie des travaux porte sur l’étude des interactions de cette tunique avec les microparticules (MP) circulantes. D’abord, nous avons montré que la présence de l’adventice modifie la réponse de la media aux MP produites in vitro à partir des lymphocytes T. Ensuite, l’étude de l’effet des MP isolées du sérum de patients en choc septique sur la media humaine a démontré que ces MP sont en mesure d’augmenter la contraction de la media par un mécanisme impliquant une diminution du NO et une augmentation de l’expression de l’ARN messager de l’interleukine-10. L’incubation de la media reconstruite avec cette cytokine anti-inflammatoire bloque l’hyporéactivité induite par les lipopolysaccharides. Le même phénomène a été reproduit in vivo, chez le rongeur. Ces résultats suggèrent que les SMP auraient un effet protecteur sur la fonction vasculaire, en potentialisant la contraction de la media. Ensuite, nous avons optimisé l’approche de reconstruction de prothèses vasculaires par auto-assemblage proposée initialement pour l’adapter au contexte particulier des CML. L’objectif principal était de permettre l’étude physiopathologique de la media à partir de toutes les lignées de CML; indépendamment de leur capacité de synthèse de matrice extracellulaire. Pour ce faire, nous avons développé un échafaudage de matrice extracellulaire produit par auto-assemblage à partir de fibroblastes humains. L’utilisation de cet échafaudage génère une media plus résistante et plus contractile que la technique initiale. Enfin, une anisotropie a été créée dans cet échafaudage pour permettre une orientation physiologique des CML. La media reconstruite devient ainsi plus résistante et plus contractile. Ces améliorations permettent de reconstruire des media à partir des cellules de plus de patients et mèneront à des études pharmacologiques plus représentatives de la population. Cet échafaudage facilitera la translation clinique de ce modèle de media reconstruite par génie tissulaire.

The “Great Masquerader" Strikes Again: Secondary Syphilis Presentation with Erythema Multiforme (EM)-Like Lesions

Syphilis is a sexually transmitted disease known to present with highly variable manifestations, especially when left untreated. Patients who present to Internal Medicine Departments with fever and a rash are always a diagnostic challenge since mild viral diseases and life-threatening bacterial infections may manifest themselves similarly. In the following case presentation, we describe a patient with 1 month’s duration of fever and rash on the palms of the hand and soles of the feet, in the form of erythema multiforme (EM)-like lesions. His disease was diagnosed as secondary syphilis, once again justifying its name: the “great masquerader".

Non-Celiac Gluten Sensitivity and Autoimmunity. A Case Report

Introduction, objective: To present a case report in which the finding of non-coeliac gluten sensitivity was decisive for the treatment of a complex autoimmune disease. Materials and methods: A 43-year-old woman with polyarthritis, psoriatic features, anti-SSA/Ro and anti-cyclic citrullinated peptide antibodies, with refractory course, was evaluated for gluten sensitivity despite negative serology for coeliac disease. Results: The patient carried the HLA DQ2 haplotype and duodenal biopsy showed lymphocytic enteritis. A gluten-free diet resolved the clinical picture and permitted tapering of immunosuppressive therapy. Conclusion: Non-coeliac gluten sensitivity can be associated with autoimmunity despite the absence of the specific autoantibodies of coeliac disease.

An Unusual Case of Cerebral Oedema

Hereditary angioedema (HAE) is a rare genetic disorder transmitted as an autosomal dominant trait, characterized by reduced plasma concentration or by the presence of non-functional C1 esterase inhibitor. Oedema caused by HAE mostly affects the skin and bowel and can induce swelling of genitalia. Oedema can be life threatening if it causes swelling of the larynx with obstruction of the airways. We describe the case of a 52-year-old man who presented a neurological emergency (coma), where the remarkable localization of the clinical manifestation and the unusual symptomatology hindered the correct diagnosis.

Multiple Myeloma Presenting with Distal Limb Gangrene: An Odd Case Report

Multiple myeloma (MM) is a plasmocytic malignant proliferation of a single clone resulting in an overabundance of monoclonal immunoglobulins. MM commonly presents with bone disorders, renal failure, anaemia and hypercalcaemia. Hyperviscosity syndrome is rare, as are vaso-occlusive symptoms. The authors report a dramatic case of an 80-year-old woman admitted to the emergency department with full-blown distal gangrene. The culprit turned out to be a MM, unusually presenting with symptomatic hyperviscosity and peripheral occlusive ischaemia. This catastrophic and particularly dramatic presentation is almost unprecedented, with only a few cases reported worldwide.

Paraneoplastic Polymyalgia Rheumatica as Manifestation of a Pancreatic Neuroendocrine Tumour

Autoimmune diseases may present as paraneoplastic syndrome. This is especially recognized in the case of polymyositis/dermatomyositis, but is less common in polymyalgia rheumatica. The authors describe the case of a 73-year-old man who presented with pain and stiffness of the scapular and pelvic girdles associated with asthenia lasting for a few weeks. The presence of therapeutic resistance and other atypical features directed the investigation towards the search of an occult malignancy. Patient evaluation revealed a pancreatic neuroendocrine tumour. After surgical treatment of the underlying neoplasia, the patient recovered fully with resolution of the rheumatic disease.

Adjuvant Effect of Leuprolide on Stroke: A Case report

Objectives: To contribute to current knowledge on the vascular risk of oestrogens. Materials and methods: A 44-year-old woman received a 11.25 mg Leuprolide exteneded release injection to control bleeding from a 7 cm uterine fibroid tumour; 45 days later, she had a stroke due to right frontal lobe ischaemia. Thrombolysis induced complete remission. Three years previously, while taking a birth control pill, the patient had suffered from a stroke that involved her left temporal lobe. She was heterozygous for Factor V R2 H1299R locus and homozygous for the 4G/4G mutation of the PAI-1 gene. Even though her homocysteine level was normal, the patient was homozygous for the MTHFR C677T mutation and although she had never had severe bleeding, she was also homozygous for Factor XIII V34L. Results and conclusion: This patient’s prothrombotic condition could have been enhanced by leuprolide since its stimulatory effect on oestrogen production would still have been minimally present at the time of cerebral thrombosis.

Suspecting Renal Artery Thrombosis

Renal artery thrombosis is a threatening clinical diagnosis, in which renal infarction may occur. Often misdiagnosed, for mimicking other common diseases, it should be considered in persistent flank pain to improve care and reduce morbidity. We review a case of a healthy, 57 year-old woman with renal artery thrombosis mimicking pyelonephritis and renal calculus obstruction, highlighting features of this clinical condition. An accurate diagnosis is essential for optimal management and prompts treatment, which still remains to be defined.

Free-Floating Thrombi in the Right Atrium Causing Pulmonary Embolism

A 74-year-old man presented to our Emergency Department with acute dyspnoea. His electrocardiogram showed atrial flutter with 2:1 block and a rate of 150 bpm. Initial investigations revealed a D-dimer level of 6.01 mg/dl. Based on the patient’s complaints and the high D-dimer level, computed tomography pulmonary angiography was immediately performed. This showed no evidence of pulmonary embolism, but there were pneumatic changes in the right upper lung lobe. Antibiotics treatment was started with pipracillin/tazobactam, after which the patient’s condition improved. However, on the third day after admission he developed acute dyspnoea, diaphoresis and cardiopulmonary instability immediately after defecation. To promptly confirm our clinical suspicion of pulmonary embolism, a transthoracic echocardiography was carried out. This demonstrated a worm-like, mobile mass in the right heart. The right ventricle was enlarged, and paradoxical septal motion was present, indicating right ventricular pressure overload. The systolic tricuspid valvular gradient was 56 mmHg. The patient was treated with thrombolysis. His condition was greatly clinically improved after 3 hours. After 10 days of hospitalization, the patient was discharged.

Simultaneous Occurrence of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Hashimoto’s Thyroiditis and Membranous Glomerulonephritis

Introduction: Membranous glomerulonephritis is commonly described in systemic lupus erythematosus (SLE) and hypothyroidism. Clinical presentation: We report a case of a 40-year-old woman who presented with a membranous glomerulonephritis associated with SLE, rheumatoid arthritis and hypothyroidism due to Hashimoto’s thyroiditis. Conclusions: The simultaneous occurrence of these three diseases as possible causes of membranous glomerulonephritis is extremely exceptional.

Use of Poppers (Amyl Nitrite): Unpleasant Side Effects in a Brothel

Introduction: Various agents can lead to an acquired methaemoglobinaemia (MHB) with potentially fatal consequences. There is a lack of literature on the formation of methaemoglobin (MH) in the blood after the intake of poppers (amyl nitrite). Poppers are a popular aphrodisiac agent. Case description: A 56-year-old diabetic called an ambulance after using poppers in a brothel with subsequent associated acrocyanosis, confusion and headache. The paramedics reported tachycardia and blood glucose of 3.8 mmol/l. The arterial blood gas analysis in the Emergency Department (ED) revealed a MHB of 23.1%. MH levels decreased rapidly without antidotal therapy. The patient was discharged the next day free of symptoms. Discussion: This case illustrates the potential risks of taking poppers. A wide spectrum of symptoms were present in our patient. For the differential diagnosis of acquired MHB, poppers should be considered.

Haematidrosis: The Rare Phenomenon of Sweating Blood

Objectives: Haematidrosis, also known as haematohidrosis, is a very rare condition where blood is excreted with sweat. As only a few cases have been described in the literature, we present guidelines on management of this rare phenomenon. Case: A 44-year-old man presented with self-limited and spontaneous bleeding episodes from different parts of his body. This had started 2 weeks before admission after an episode of extreme emotional stress. Medical history and laboratory tests were normal. The microscopic examination of a sample of the fluid excreted confirmed all blood elements. Conclusion: The disorder is thought to be related to activation of the sympathetic nervous system. The use of benzodiazepines and beta blockers may be helpful in controlling the bleeding episodes and give some comfort to the patient.